COMPARISON OF HYDROCORTISONE 10 MG TABLETS: TABLET HARDNESS OPTIMISED FOR ADULT USE HAS NEGATIVE CONSEQUENCES FOR PAEDIATRIC USE.

PubMed

Saimbi, Sarina; Madden, Valerie; Stirling, Heather; Yahyouche, Asma; Batchelor, Hannah

2016-09-01

Children's medicines are not always readily available as an age appropriate product and manipulation of adult products is often required. Recently the commercial manufacturing process for 10 mg hydrocortisone tablets has changed and the compression force increased due to tablets fracturing on removal from the blister pack. However, this change led to parents of children requiring hydrocortisone reporting that the tablets were more difficult to manipulate.This study evaluated 10 mg hydrocortisone tablets for their suitability for manipulation in order to deliver an appropriate dose to children (2 mg dose). The physical properties of tablets with the old and new compression force were compared as well as the accuracy of obtaining the paediatric dose. The tablets compared were hydrocortisone Auden 10 mg tablets (Brand A, PL16876/002)-these are the newer, harder tablets- and hydrocortisone 10 mg tablets (Brand B, PL17507/0097). Tablet physical properties including friability (Copley FRV200) and tablet hardness (Copley TBF1000) were compared. The accuracy of split doses (halve and quarter tablets) were recorded on a Sartorius analytical balance. The accuracy of the 2 mg paediatric dosing was assessed by crushing the tablet, adding 10 mL of water and extracting 2 mL. The concentration was measured using UV analysis (Jenway Genova Plus) according to a calibration curve (wavelength=246 nm). Two devices were used to crush the tablets: a spoon onto a plate and a commercially available crushing device (Apothecary Ezy Crush Pill Crusher With Ergo Grip). As anticipated Brand A tablets were harder (51.85 ±5.1 N) compared to Brand B (30.99±4.1 N). Brand A tablets passed the friability testing with <1% weight loss whereas Brand B failed as 5 tablets broke during testing.The accuracy of split doses using the score lines to halve and quarter the tablets showed that Brand A were generally better with smaller ranges for both halves (Range for A=41-55%; B=29-70%) and quarters (Range for A=17-35%; B=12-42%) compared to Brand B.The 2 mg dosing accuracy was better for Brand B tablets compared to A and crushing tablets using a commercial device improved the accuracy of dosing for both brands of tablets. When crushing using a spoon the mean dose obtained was 1.3 mg for Brand A and 1.7 mg for Brand B; the commercial crushing device gave values of 1.9 mg for Brand A and 2.1 mg for Brand B. Parents or carers who are required to manipulate 10 mg hydrocortisone tablets to administer a dose to children dispersed in water should be advised to crush the tablet into a fine powder where possible to improve the likelihood of administering an accurate dose. This is particularly important since the introduction of new hydrocortisone Auden tablets which are known to be harder tablets and therefore more force is required to crush these. Some of the experimental work within this project was conducted by Andrew Hackett and Kameron Paul-Thaper whilst at the University of Birmingham on work experience from Arden Sixth Form, Station Rd, Knowle, Solihull, West Midlands, B93 0PT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Influence of Carbopol 71G-NF on the release of dextromethorphan hydrobromide from extended-release matrix tablets.

PubMed

Fayed, Mohamed H; Mahrous, Gamal M; Ibrahim, Mohamed A; Sakr, Adel

2013-01-01

The objective of this study was to evaluate the potential of Carbopol(®) 71G-NF on the release of dextromethorphan hydrobromide (DM) from matrix tablets in comparison with hydroxypropyl methylcellulose (HPMC(®) K15M) and Eudragit(®) L100-55 polymers. Controlled release DM matrix tablets were prepared using Carbopol 71G-NF, HPMC K15M, and Eudragit L100-55 at different drug to polymer ratios by direct compression technique. The mechanical properties of the tablets as tested by crushing strength and friability tests were improved as the concentration of Carbopol, HPMC, and Eudragit increased. However, Carbopol-based tablets showed a significantly (P<0.05) higher crushing strength and a lower friability than HPMC and Eudragit tablets. No significant differences in weight uniformity and thickness values were observed between the different formulations. It was also found that Carbopol significantly (P<0.05) delayed the release of DM in comparison with HPMC K15M and Eudragit L100-55. A combination of HPMC K15M and Eudragit L100-55 in a 1:1 ratio at 20 and 30% significantly (P<0.05) delayed the release of DM than Eudragit L100-55 alone. Moreover, blends of Carbopol and HPMC at a 1:1 ratio at the 10, 20, and 30% total polymer concentration were investigated. The blend of Carbopol and HPMC at 10% level significantly (P<0.05) slowed the release of DM than Carbopol or HPMC alone, whereas blends at 20 and 30% level significantly (P<0.05) delayed the release of DM compared with HPMC or Carbopol alone. The results with these polymer blends showed that it was possible to reduce the total amount of polymers when used as a combination in formulation.

Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--part 1--acetaminophen.

PubMed

Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

2009-03-01

The aim of this study was to characterize and evaluate a modified release, multiparticulate tablet formulation consisting of placebo beads and drug-loaded beads. Acetaminophen (APAP) bead formulations containing ethylcellulose (EC) from 40-60% and placebo beads containing 30% calcium silicate and prepared using 0-20% alcohol were developed using extrusion-spheronization and studied using a central composite experimental design. Particle size and true density of beads were measured. Segregation testing was performed using the novel ASTM D6940-04 method on a 50:50 blend of uncoated APAP beads (60%EC) : calcium silicate placebo beads (10% alcohol). Tablets were prepared using an instrumented Stokes-B2 rotary tablet press and evaluated for crushing strength and dissolution rate. Compared with drug beads (60%EC), placebo beads (10% alcohol) were smaller but had higher true densities: 864.8 mum and 1.27 g/cm(3), and 787.1 mum and 1.73 g/cm(3), respectively. Segregation testing revealed that there was approximately a 20% difference in drug content (as measured by the coefficient of variation) between initial and final blend samples. Although calcium silicate-based placebo beads were shown to be ineffective cushioning agents in blends with Surelease(R)-coated APAP beads, they were found to be very compactibile when used alone and gave tablet crushing strength values between 14 and 17 kP. The EC in the APAP bead matrix minimally suppressed the drug release from uncoated beads (t(100%) = 2 h). However, while tablets containing placebo beads reformulated with glycerol monostearate (GMS) showed a slower release rate (t(60%)= 5 h) compared with calcium silicate-based placebos, some coating damage ( approximately 30%) still occurred on compression as release was faster than coated APAP beads alone. While tablets containing coated drug beads can be produced with practical crushing strengths (>8 kP) and low compression pressures (10-35 MPa), dissolution studies revealed that calcium silicate-based placebos are ineffective as cushioning agents. Blend segregation was likely observed due to the particle size and the density differences between APAP beads and calcium silicate-based placebo beads; placebo bead percolation can perhaps be minimized by increasing their size during the extrusion-spheronization process. The GMS- based placebos offer greater promise as cushioning agents for compacted, coated drug beads; however, this requires an optimized compression pressure range and drug bead : placebo bead ratio (i.e., 50:50).

Challenges in detecting magnesium stearate distribution in tablets.

PubMed

Lakio, Satu; Vajna, Balázs; Farkas, István; Salokangas, Henri; Marosi, György; Yliruusi, Jouko

2013-03-01

Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a well-known problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.

NEW METHODOLOGY FOR DEVELOPMENT OF ORODISPERSIBLE TABLETS USING HIGH-SHEAR GRANULATION PROCESS.

PubMed

Ali, Bahaa E; Al-Shedfat, Ramadan I; Fayed, Mohamed H; Alanazi, Fars K

2017-05-01

Development of orodispersible delivery system of high mechanical properties and low disintegration time is a big challenge. The aim of the current work was to assess and optimize the high shear granulation process as a new methodology for development of orodispersible tablets of high quality attributes using design of experiment approach. A two factor, three levels (32), full factorial design was carried out to investigate the main and interaction effects of independent variables, water amount (XI) and granulation time (X2) on the characteristics of granules and final product, tablet. The produced granules were analyzed for their granule size, density and flowability. Furthermore, the produced tablets were tested for: weight variation, breaking force/ crushing strength, friability, disintegration time and drug dissolution. Regression analysis results of multiple linear models showed a high correlation between the adjusted R-squared and predicted R-squared for all granules and tablets characteristics, the difference is less than 0.2. All dependent responses of granules and tablets were found to be impacted significantly (p < 0.05) by the two independent variables. However, water amount demonstrated the most dominant effect for all granules and tablet characteristics as shown by higher its coefficient estimate for all selected responses. Numerical optimization using desirability function was performed to optimize the variables under study to provide orodispersible system within the USP limit with respect of mechanical properties and disintegration time. It was found that the higher desirability (0.915) could be attained at the low level pf water (180 g) and short granulation time (1.65 min). Eventually, this study provides the formulator with helpful information in selecting the proper level of water and granulation time to provide an orodispersible system of high crushing strength and very low disintegration time, when high shear granulation methodology was used as a method of manufacture.

Evaluation of the Disintegrant Properties of Native Starches of Five New Cassava Varieties in Paracetamol Tablet Formulations

PubMed Central

Adjei, Frank Kumah; Osei, Yaa Asantewaa; Kuntworbe, Noble

2017-01-01

The disintegrant potential of native starches of five new cassava (Manihot esculenta Crantz.) varieties developed by the Crops Research Institute of Ghana (CRIG) was studied in paracetamol tablet formulations. The yield of the starches ranged from 8.0 to 26.7%. The starches were basic (pH: 8.1–9.9), with satisfactory moisture content (≤15%), swelling capacity (≥20%), ash values (<1%), flow properties, and negligible toxic metal ion content, and compatible with the drug. The tensile strength (Ts), crushing strength (Cs), and friability (Ft) of tablets containing 5–10% w/w of the cassava starches were similar (p > 0.05) to those containing maize starch BP. The disintegration times of the tablets decreased with increase in concentration of the cassava starches. The tablets passed the disintegration test (DT ≤ 15 min) and exhibited faster disintegration times (p > 0.05) than those containing maize starch BP. The disintegration efficiency ratio (DER) and the disintegration parameter DERc of the tablets showed that cassava starches V20, V40, and V50 had better disintegrant activity than maize starch BP. The tablets passed the dissolution test for immediate release tablets (≥70% release in 45 min) with dissolution rates similar to those containing maize starch BP. PMID:28781909

Hexagonal boron nitride as a tablet lubricant and a comparison with conventional lubricants.

PubMed

Uğurlu, Timuçin; Turkoğlu, Murat

2008-04-02

The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) as a new tablet lubricant and compare it with conventional lubricants such as magnesium stearate (MGST), stearic acid (STAC), and glyceryl behenate (COMP). Tablets were manufactured on an instrumented single-station tablet press to monitor lower punch ejection force (LPEF) containing varied lubricants in different ratio (0.5, 1, 2%). Tablet crushing strength, disintegration time and thickness were measured. Tensile strength of compacted tablets were measured by applying a diametrical load across the edge of tablets to determine mechanical strength. The deformation mechanism of tablets was studied during compression from the Heckel plots with or without lubricants. MGST was found to be the most effective lubricant based on LPEF-lubrication concentration profile and LPEF of HBN was found very close to that of MGST. HBN was better than both STAC and COMP. A good lubrication was obtained at 0.5% for MGST and HBN (189 and 195N, respectively). Where COMP and STAC showed 20 and 35% more LPEF compare to that of MGST (239 and 288N, respectively). Even at the concentration of 2% COMP and STAC did not decrease LPEF as much as 0.5% of MGST and HBN. Like all conventional lubricants the higher the concentration of HBN the lower the mechanical properties of tablets because of its hydrophobic character. However, this deterioration was not as pronounced as MGST. HBN had no significant effect on tablet properties. Based on the Heckel plots, it was observed that after the addition of 1% lubricant granules showed less plastic deformation.

Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo.

PubMed

Crean, Barry; Finnie, Cindy; Crosby, Anna

2013-06-01

Orally available ticagrelor in combination with low-dose aspirin (75-100 mg/day) is indicated for adult patients with acute coronary syndromes. However, patients with swallowing difficulties may be unable to consume the currently available 90-mg tablet. It is hypothesized that ticagrelor could be given to this patient cohort as a crushed dose administered either orally or via a naso-gastric (NG) tube. To investigate the potential use of crushed ticagrelor tablets (90- and 180-mg doses) for oral dose or NG tube administration. Ticagrelor tablets (90 or 180 mg [two 90-mg tablets]) were prepared to emulate oral and NG tube administration by similar methods. For the oral dose, ticagrelor tablets were crushed using a mortar and pestle and transferred to a dosing cup. 100 mL of water was added to the mortar, stirred, and the contents were transferred to the dosing cup and stirred to form a suspension. At this stage, where the suspension would normally be administered to a patient, it was collected for high performance liquid chromatography (HPLC) analysis. The mortar was then flushed with 100 mL of water, and the contents were again transferred to the dosing cup, stirred, and collected for HPLC analysis. For the NG dose, polyvinylchloride, polyurethane, and silicone size CH10 NG tubes were used. The tablets were crushed using a mortar and pestle, diluted with 50 mL of water, and stirred. At this stage, where the suspension would normally be administered to a patient through an NG tube using a syringe, it was collected for HPLC analysis. The mortar was then flushed with two additional 50 mL aliquots of water and the contents were passed through the NG tube. HPLC analysis examined the recoverability of ticagrelor in each of the dose suspensions and flushes and the stability of the suspension when held in a syringe for up to 2 h. One or two crushed 90-mg ticagrelor tablets, prepared for either oral or NG tube administration, delivers a mean dose of ≥97% of the original tablet. No degradation of the suspensions was detected after ticagrelor had been held in the syringe for up to 2 h. Although not an approved method of administration, these results suggest that ticagrelor tablets can be crushed and prepared for oral administration or for administration via an NG tube. From a clinical perspective, a syringe hold-time of up to 2 h should allow for enough time between preparation and administration (orally or via an NG tube) of the dispersed tablets to the patient. Future studies are required to test the effect of crushed dosing on pharmacokinetic and pharmacodynamic parameters.

A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers.

PubMed

Sunkaraneni, Soujanya; Kharidia, Jahnavi; Schutz, Ralph; Blum, David; Cheng, Hailong

2016-07-01

The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC(0-∞) and Cmax were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to-treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average Cmax , 11 700 versus 11 500 ng/mL; AUC(0-∞) , 225 000 versus 234 000 ng·h/mL; AUC(0-last) , 222 000 versus 231 000 ng·h/mL, respectively. Geometric least squares mean ratios (90%CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (Cmax , 102.63% [97.07%-108.51%]; AUC(0-∞) , 96.72% [94.36%-99.13%]; AUC0-last , 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed. © 2016, The American College of Clinical Pharmacology.

Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view.

PubMed

Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

2016-02-29

Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength. Copyright © 2015 Elsevier B.V. All rights reserved.

Novel platens to measure the hardness of a pentagonal shaped tablet.

PubMed

Malladi, Jaya; Sidik, Kurex; Wu, Sutan; McCann, Ryan; Dougherty, Jeffrey; Parab, Prakash; Carragher, Thomas

2017-03-01

Tablet hardness, a measure of the breaking force of a tablet, is based on numerous factors. These include the shape of the tablet and the mode of the application of force. For instance, when a pentagonal-shaped tablet was tested with a traditional hardness tester with flat platens, there was a large variation in hardness measurements. This was due to the propensity of vertices of the tablet to crush, referred to as an "improper break". This article describes a novel approach to measure the hardness of pentagonal-shaped tablets using modified platens. The modified platens have more uniform loading than flat platens. This is because they reduce loading on the vertex of the pentagon and apply forces on tablet edges to generate reproducible tablet fracture. The robustness of modified platens was assessed using a series of studies, which included feasibility and Gauge Repeatability & Reproducibility (R&R) studies. A key finding was that improper breaks, generated frequently with a traditional hardness tester using flat platens, were eliminated. The Gauge R&R study revealed that the tablets tested with novel platens generated consistent values in hardness measurements, independent of batch, hardness level, and day of testing, operator and tablet dosage strength.

Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects.

PubMed

Song, Yan; Wang, Xiaoli; Perlstein, Itay; Wang, Jessie; Badawy, Sherif; Frost, Charles; LaCreta, Frank

2015-08-01

Crushed tablet and solution formulations of apixaban administered orally or via a nasogastric tube (NGT) may be useful in patients unable to swallow solid dose formulations. It is important to understand whether new formulations and/or methods of administration impact apixaban bioavailability and pharmacokinetic properties. These studies evaluated the relative bioavailability (Frel) of apixaban solution administered orally; oral solution administered via NGT flushed with either 5% dextrose in water (D5W) or with infant formula; oral solution via NGT with a nutritional supplement; and crushed tablet suspended in D5W and administered via NGT. Three open-label, randomized, crossover studies were conducted in healthy adults (study 1: apixaban 10-mg tablet [reference] versus oral solution, both administered PO; study 2: apixaban 5-mg oral solution PO [reference] versus oral solution via NGT flushed with either D5W or infant formula; study 3: apixaban 5-mg oral solution PO [reference] versus apixaban 5-mg oral solution via NGT with a nutritional supplement and versus crushed tablet suspended in D5W and administered via NGT). Point estimates and 90% CIs of the geometric mean ratios (GMRs; test/reference) were generated for Cmax and AUC. Adverse events were recorded throughout each study. Frel of the oral solution was 105% versus tablet, and Frel for oral solution via NGT with D5W flush, infant formula flush, nutritional supplement, and crushed tablet via NGT versus oral solution administration were 96.7%, 92.2%, 81.3%, and 95.1%, respectively. The 90% CIs of the GMRs of all AUCs met the bioequivalence criterion except that of the nutritional supplement (0.766-0.863). The corresponding GMRs for Cmax were 0.977, 0.953, 0.805, 0.682, and 0.884. For the solution via NGT flushed with D5W and for the crushed tablet, the 90% CIs of the Cmax GMRs met the bioequivalence criterion. Apixaban was well tolerated in all 3 studies; most adverse events were mild. Comparable Frel was observed for oral apixaban solution, tablet, NGT administration of solution flushed with D5W and infant formula, and NGT administration of crushed tablet suspension. Exposure was less when oral solution was administered via NGT with nutritional supplement. These results support several alternative methods of administering apixaban that may be useful in certain clinical situations. ClinicalTrials.gov identifiers: NCT02034565, NCT02034578, and NCT02034591. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pharmacokinetic and pharmacodynamic characteristics of a new pediatric formulation of artemether-lumefantrine in African children with uncomplicated Plasmodium falciparum malaria.

PubMed

Djimdé, Abdoulaye A; Tekete, Mamadou; Abdulla, Salim; Lyimo, John; Bassat, Quique; Mandomando, Inacio; Lefèvre, Gilbert; Borrmann, Steffen

2011-09-01

The pharmacokinetic and pharmacodynamic properties of a new pediatric formulation of artemether-lumefantrine, dispersible tablet, were determined within the context of a multicenter, randomized, parallel-group study. In an exploratory approach, we compared a new pediatric formulation with the tablet formulation administered crushed in the treatment of African children with uncomplicated Plasmodium falciparum malaria. Patients were randomized to 3 different dosing groups (weights of 5 to <15 kg, 15 and <25 kg, and 25 to <35 kg). Treatment was administered twice daily over 3 days. Plasma concentrations of artemether and its active metabolite, dihydroartemisinin (DHA), were determined at 1 and 2 h after the first dose of dispersible (n = 91) and crushed (n = 93) tablets. A full pharmacokinetic profile of lumefantrine was reconstituted on the basis of 310 (dispersible tablet) and 315 (crushed tablet) plasma samples, collected at 6 different time points (1 sample per patient). Dispersible and crushed tablets showed similar artemether and DHA maximum concentrations in plasma (C(max)) for the different body weight groups, with overall means of 175 ± 168 and 190 ± 168 ng/ml, respectively, for artemether and 64.7 ± 58.1 and 63.7 ± 65.0 ng/ml, respectively, for DHA. For lumefantrine, the population C(max) were 6.3 μg/ml (dispersible tablet) and 7.7 μg/ml (crushed tablet), whereas the areas under the concentration-time curves from time zero to the time of the last quantifiable plasma concentration measured were 574 and 636 μg · h/ml, respectively. For both formulations, descriptive quintile analyses showed no apparent association between artemether/DHA C(max) and parasite clearance time or between the lumefantrine C(max) and the occurrence of adverse events or corrected QT interval changes. The results suggest that the dispersible tablet provides adequate systemic exposure to artemether, DHA, and lumefantrine in African children with uncomplicated P. falciparum malaria.

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.

PubMed

Chua, Hui Ming; Hauet Richer, Nathalie; Swedrowska, Magda; Ingham, Stephen; Tomlin, Stephen; Forbes, Ben

2016-01-07

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

Treatment of Chronic Hepatitis C Virus Infection With Crushed Ledipasvir/Sofosbuvir Administered via a Percutaneous Endoscopic Gastrostomy Tube.

PubMed

Jindracek, Lauren; Stark, Jennifer

2017-01-01

Ledipasvir/sofosbuvir (Harvoni®) is a fixed-dose tablet indicated for the treatment of chronic hepatitis C virus (HCV) infection. There are currently no data available on the safety and efficacy of crushed ledipasvir/sofosbuvir tablets. This report describes the first documented case of successful treatment of chronic HCV infection in a patient crushing ledipasvir/sofosbuvir for administration via a percutaneous endoscopic gastrostomy (PEG) tube. The patient was treatment experienced and had evidence of compensated cirrhosis. Treatment duration was 24 weeks, and HCV RNA was undetectable 12 weeks after completion of treatment (SVR12) which is the accepted measure of a clinical cure. Issues may arise during or prior to starting HCV treatment that necessitate crushing tablets. Stopping or interrupting HCV treatment could lead to development of resistance or treatment failure. This is the first published case in which crushed ledipasvir/sofosbuvir administered via a PEG tube is documented as a safe and effective option for treatment of chronic HCV infection.

Substituted amylose matrices for oral drug delivery

NASA Astrophysics Data System (ADS)

Moghadam, S. H.; Wang, H. W.; Saddar El-Leithy, E.; Chebli, C.; Cartilier, L.

2007-03-01

High amylose corn starch was used to obtain substituted amylose (SA) polymers by chemically modifying hydroxyl groups by an etherification process using 1,2-epoxypropanol. Tablets for drug-controlled release were prepared by direct compression and their release properties assessed by an in vitro dissolution test (USP XXIII no 2). The polymer swelling was characterized by measuring gravimetrically the water uptake ability of polymer tablets. SA hydrophilic matrix tablets present sequentially a burst effect, typical of hydrophilic matrices, and a near constant release, typical of reservoir systems. After the burst effect, surface pores disappear progressively by molecular association of amylose chains; this allows the creation of a polymer layer acting as a diffusion barrier and explains the peculiar behaviour of SA polymers. Several formulation parameters such as compression force, drug loading, tablet weight and insoluble diluent concentration were investigated. On the other hand, tablet thickness, scanning electron microscope analysis and mercury intrusion porosimetry showed that the high crushing strength values observed for SA tablets were due to an unusual melting process occurring during tabletting although the tablet external layer went only through densification, deformation and partial melting. In contrast, HPMC tablets did not show any traces of a melting process.

Compression parameters of hexagonal boron nitride on direct compression mixture of microcrystalline cellulose and modified starch.

PubMed

Halaçoğlu, Mekin Doğa; Uğurlu, Timuçin

2015-01-01

The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant "hexagonal boron nitride (HBN)" on direct compression powders. Lubricants such as magnesium stearate (MGST), glyceryl behenate, stearic acid, talc and polyethylene glycol6000 were studied and tablets were manufactured on a single station instrumented tablet press. This study comprised the continuation of our previous one, so mixture of microcrystalline cellulose and modified starch was used as a master formula to evaluate effects of lubricants on pharmaceutical excipients that undergo complete plastic deformation without any fragmentation under compression pressure. Bulk and tapped densities, and Carr's index parameters were calculated for powders. Tensile strength, cohesion index, lower punch ejection force and lubricant effectiveness values were investigated for tablets. The deformation mechanisms of tablets were studied during compression from the Heckel plots with or without lubricant. MGST was found to be the most effective lubricant and HBN was found very close to it. HBN did not show a significant negative effect on the crushing strength and disintegration time of the tablets when we compared with MGST. Based on the Heckel plots at the level of 1%, formulation prepared with HBN showed the most pronounced plastic character.

Pharmacology of ketoconazole suspension in infants and children.

PubMed Central

Ginsburg, C M; McCracken, G H; Olsen, K

1983-01-01

The pharmacokinetics of ketoconazole administered as either a commercially prepared suspension or as a crushed tablet in applesauce were studied in 12 children. The mean peak plasma concentration of ketoconazole and the area under the plasma time-concentration curve were approximately twofold greater with the suspension than with the crushed tablets. PMID:6307138

Bioequivalence of ximelagatran, an oral direct thrombin inhibitor, as whole or crushed tablets or dissolved formulation.

PubMed

Schützer, Kajs-Marie; Wall, Ulrika; Lönnerstedt, Carina; Ohlsson, Lis; Teng, Renli; Sarich, Troy C; Eriksson, Ulf G

2004-03-01

To investigate whether crushed or dissolved tablets of the oral direct thrombin inhibitor ximelagatran are bioequivalent to whole tablet administration. Ximelagatran is currently under development for the prevention and treatment of thromboembolic disorders. This was an open-label, randomised, three-period, three-treatment crossover study in which 40 healthy volunteers (aged 20-33 years) received a single 36-mg dose of ximelagatran administered in three different ways: I swallowed whole, II crushed, mixed with applesauce and ingested and III dissolved in water and administered via nasogastric tube. The plasma concentrations of ximelagatran, its intermediates and the active form melagatran were determined. Ximelagatran was rapidly absorbed and the bioavailability of melagatran was similar after the three different administrations, fulfilling the criteria for bioequivalence. The mean area under the plasma concentration-versus-time curve (AUC) of melagatran was 1.6 micromol.h/L (ratio 1.01 for treatment II/I and 0.97 for treatment III/I), the mean peak concentration (C(max)) was 0.3 micromol/L (ratio 1.04 for treatment II/I and 1.02 for treatment III/I) and the mean half-life (t(1/2)) was 2.8 h for all treatments. The time to C(max) (t(max)) was 2.2h for the whole tablet and approximately 0.5 h earlier when the tablet was crushed or dissolved (1.7-1.8 h), due to a more rapid absorption. The study drug was well tolerated as judged from the low incidence and type of adverse events reported. The present study showed that the pharmacokinetics (AUC and C(max)) of melagatran were not significantly altered whether ximelagatran was given orally as a crushed tablet mixed with applesauce or dissolved in water and given via nasogastric tube.

[The use of semi-synthetic polymers in the formulation of sucking and chewable tablets containing sage extract and zinc gluconate].

PubMed

Linka, Wojciech Andrzej; Golenia, Ewa; Zgoda, Marian Mikołaj; Kołodziejczyk, Michał Krzysztof

2014-01-01

Halitosis and gingivitis are most common pathologies (15-60% of population) which, if left untreated, lead to periodontal diseases and tooth loss. The aim of this study was to develop, based on polymers of dry sage extract and zinc gluconate, tablets intended for sucking and chewing that can be applied in the treatment of halitosis and gingivitis. Dried aqueous sage extract, zinc gluconate, Pharmagum M, Prosolv SMCC90 and SMCCHD90, Vivapur 102, sorbitol, mannitol, ludipress. Direct tableting. Testing pharmacopeial parameters and pharmaceutical availability (using basket and rotating disk methods) of tablets intended for sucking and chewing. Approximation of the obtained results. Grey and green color tablets were obtained with smooth and uniform surface, without stains, spalls or mechanical damage. The determined average mass (weight) of a tablet complied with the standard. The friability and crushing strength test revealed that tablets containing Prosolv SMCCHD90, Vivapur 102 and mannitol demonstrated the highest mechanical strength. Tablets containing these substances and intended for sucking had prolonged disintegration and release time. Tablets intended for chewing had a hardness at the level of 124 N.They demonstrated compressibility, low friability and prolonged release. The release profiles of tablets intended for sucking (v2) and those for chewing, obtained by basket and rotating disk methods, were similar. The addition of Prosolv SMCCHD90, Vivapur 102 and mannitol increased significantly the mechanical strength (higher hardness, lower friability), prolonged the disintegration time and slowed the release from the obtained tablets intended for sucking and chewing. The application of Prosolv SMCCHD90 in the formulation of tablets for chewing carries the risk for sorption of active components to the polymer structure. This process takes place in the early stage of the release. Rotating disk method used in pharmaceutical availability testing gives better results while analyzing the phenomenon than the standard basket method. The suggested and tested formulations of tablets intended for sucking and chewing may be used as an alternative to formulations containing dried titrated extracts from plants of antimicrobial activity (sage - Salvia officinalis) in combination with substances binding volatile sulfur compounds (zinc gluconate).

Phosphate-binding efficacy of crushed vs. chewed lanthanum carbonate in hemodialysis patients.

PubMed

How, Priscilla P; Anattiwong, Prathana; Mason, Darius L; Arruda, Jose A; Lau, Alan H

2011-01-01

Lanthanum carbonate, a chewable noncalcium-containing phosphorus (P) binder, is useful for treating secondary hyperparathyroidism in patients who have hypercalcemia and cannot swallow whole tablets. However, some patients cannot chew tablets or prefer to crush and mix them with food. This study was conducted to determine the P-binding efficacy of crushed lanthanum and compare it with chewed lanthanum in hemodialysis (HD) patients. After a 1-week washout period, 11 hemodialysis patients (7 men, 4 women) were randomized to receive, in a crossover fashion, lanthanum 1000 mg 3 times daily chewed with meals and lanthanum 1000 mg 3 times daily crushed into a fine powder, mixed with applesauce and taken with meals, for 4 weeks each. Serum P was measured at the end of each washout (baseline) and weekly during treatment. Changes in serum P from baseline for crushed lanthanum were compared with chewed lanthanum using paired sample t test. Administration of crushed lanthanum resulted in a significant reduction in serum P from baseline (P reduction [mg/dL] for crushed lanthanum in week 1: 2.1 ± 0.4, week 2: 1.7 ± 0.5, week 3: 1.7 ± 0.5, week 4: 1.7 ± 0.4, P<0.05). No statistically significant differences were observed in serum P reduction from baseline and serum P attained during treatment with crushed when compared with chewed lanthanum. Crushed lanthanum is effective in reducing serum P and have similar P-binding efficacy to chewed lanthanum. Crushing lanthanum and mixing it with food can thus be an option for patients who are unable to chew or swallow whole tablets. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

Daily Average Consumption of 2 Long-Acting Opioids: An Interrupted Time Series Analysis

PubMed Central

Puenpatom, R. Amy; Szeinbach, Sheryl L.; Ma, Larry; Ben-Joseph, Rami H.; Summers, Kent H.

2012-01-01

Background Oxycodone controlled release (CR) and oxymorphone extended release (ER) are frequently prescribed long-acting opioids, which are approved for twice-daily dosing. The US Food and Drug Administration approved a reformulated crush-resistant version of oxycodone CR in April 2010. Objective To compare the daily average consumption (DACON) for oxycodone CR and for oxymorphone ER before and after the introduction of the reformulated, crush-resistant version of oxycodone CR. Methods This was a retrospective claims database analysis using pharmacy claims from the MarketScan database for the period from January 2010 through March 2011. The interrupted time series analysis was used to evaluate the impact of the introduction of reformulated oxycodone CR on the DACON of the 2 drugs—oxycodone CR and oxymorphone ER. The source of the databases included private-sector health data from more than 150 medium and large employers. All prescription claims containing oxycodone CR and oxymorphone ER dispensed to members from January 1, 2010, to March 31, 2011, were included in the analysis. Prescription claims containing duplicate National Drug Codes, missing member identification, invalid quantities or inaccurate days supply of either drug, and DACON values of <1 and >500 were removed. Results The database yielded 483,063 prescription claims for oxycodone CR and oxymorphone ER from January 1, 2010, to March 31, 2011. The final sample consisted of 411,404 oxycodone CR prescriptions (traditional and reformulated) dispensed to 85,150 members and 62,656 oxymorphone ER prescriptions dispensed to 11,931 members. Before the introduction of reformulated oxycodone CR, DACON values for the highest strength available for each of the 2 drugs were 0.51 tablets higher for oxycodone CR than for oxymorphone ER, with mean DACON values of 3.5 for oxycodone CR and 3.0 for oxymorphone ER (P <.001). The differences of mean DACON between the 2 drugs for all lower strengths were 0.46 tablets, with mean DACON values of 2.7 for oxycodone CR and 2.3 for oxymorphone ER (P <.001). After the introduction of the new formulation, the difference in mean DACON between the 2 drugs was slightly lower: 0.45 tablets for the highest-strength and 0.40 tablets for the lower-strength pairs. Regression analyses showed that the immediate and overall impact of the reformulation of oxycodone CR on the DACON of oxycodone CR was minimal, whereas no changes were seen in the DACON of oxymorphone ER. The estimated DACON for oxycodone CR decreased by 0.1 tablets, or 3.7% (P <.001), 6 months after the new formulation was introduced. Conclusion The mean DACON was 0.4 tablets per day higher for oxycodone CR compared with oxymorphone ER for all dosage strengths for the entire study period. After the introduction of the reformulated oxycodone CR, the DACON for this drug was slightly mitigated; however, there was a minimal impact on the mean differences between oxycodone CR and oxymorphone ER. PMID:24991311

HIGH-SHEAR GRANULATION PROCESS: INFLUENCE OF PROCESSING PARAMETERS ON CRITICAL QUALITY ATTRIBUTES OF ACETAMINOPHEN GRANULES AND TABLETS USING DESIGN OF EXPERIMENT APPROACH.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shedfat, Ramadan I

2017-01-01

Application of quality by design (QbD) in high shear granulation process is critical and need to recognize the correlation between the granulation process parameters and the properties of intermediate (granules) and corresponding final product (tablets). The present work examined the influence of water amount (X,) and wet massing time (X2) as independent process variables on the critical quality attributes of granules and corresponding tablets using design of experiment (DoE) technique. A two factor, three level (32) full factorial design was performed; each of these variables was investigated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their size distribution, density and flow pattern. Additionally, the produced tablets have been investigated for weight uniformity, crushing strength, friability and percent capping, disintegration time and drug dissolution. Statistically significant impact (p < 0.05) of water amount was identified for granule growth, percent fines and distribution width and flow behavior. Granule density and compressibility were found to be significantly influenced (p < 0.05) by the two operating conditions. Also, water amount has significant effect (p < 0.05) on tablet weight unifornity, friability and percent capping. Moreover, tablet disintegration time and drug dissolution appears to be significantly influenced (p < 0.05) by the two process variables. On the other hand, the relationship of process parameters with critical quality attributes of granule and final product tablet was identified and correlated. Ultimately, a judicious selection of process parameters in high shear granulation process will allow providing product of desirable quality.

Efficacy of chewed vs. crushed lanthanum on phosphorus binding in healthy volunteers.

PubMed

How, P P; Mason, D L; Arruda, J A; Lau, A H

2010-05-01

For effective dietary phosphorous (P) binding, patients are recommended to chew lanthanum tablets completely before swallowing, with or immediately after meals. However, some patients are unable to chew the tablets. It is not known if crushing the tablets prior to taking them with food is as efficacious as chewing them. This study was conducted to compare the efficacy of chewed vs. crushed lanthanum on P binding. 12 healthy subjects were randomized and crossed-over to receive: (A) a standardized meal containing 1 g (32 mmol) of elemental P; (B) a single 1 g oral dose of lanthanum, chewed and taken with the standardized meal; (C) a single 1 g oral dose of lanthanum, crushed into a fine powder using a pestle and mortar, mixed with applesauce, and taken with the standardized meal. Blood and urine samples were collected from baseline to 8 hours after meal completion. The changes in serum P, urinary P excretion and fractional excretion of P (FePi) were compared among treatment arms using ANOVA. Co-administration of lanthanum with meal resulted in a smaller increase in serum P, compared with meal alone (p < 0.05). The smaller increase in serum P was similar for both chewed and crushed lanthanum. The amount of P excreted and FePi were also lower when chewed or crushed lanthanum was administered with meal, compared with meal alone (p = n.s. and p < 0.05, respectively). Both chewed and crushed lanthanum are effective in lowering P absorption after a dietary P load.

Chitinosans as tableting excipients for modified release delivery systems.

PubMed

Rege, P R; Shukla, D J; Block, L H

1999-04-20

The term 'chitinosans' embraces the spectrum of acetylated poly(N-glucosamines) ranging from chitin to chitosan. Chitinosans (I), at acidic pH, have protonated amines which can interact with oppositely charged drug ions and, thereby, modify drug release from drug delivery systems. Tablets were compressed from a physical mixture containing salicylic acid (II) as the model drug, I, and magnesium stearate. Five commercial I compounds, varying in degree of deacetylation and molecular weight, were selected. Tablets were compressed at 5000, 10 000, and 15 000 psig using a Carver and a single punch tablet press. The differential scanning calorimetry thermograms provided evidence of I-II interaction in the powder blend. Analysis of variance (ANOVA) indicated that the compression pressure did not significantly affect the crushing strength (CS) or the release profile of II from the I-matrix tablets (P?0.05). Furthermore, the ANOVA also indicated that the tablet press used during manufacture did not affect the above properties (P?0.05); however, the chitinosans significantly affected the CS as well as the release profile of II from I-matrix tablets (P<0.05). This study provides further evidence for the use of commercial I compounds as excipients for use in modified release drug delivery systems. Copyright.

Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics.

PubMed

El-Say, Khalid M; Ahmed, Tarek A; Abdelbary, Maged F; Ali, Bahaa E; Aljaeid, Bader M; Zidan, Ahmed S

2015-12-01

This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for pre- and post-compression characteristics. The prepared OD-mini-tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

Alfuzosin

MedlinePlus

Alfuzosin comes as an extended-release (long-acting) tablet to take by mouth. It is usually taken ... often than prescribed by your doctor.Swallow the tablets whole; do not split, chew, or crush them. ...

Development and evaluation of Ca(+ 2) ion cross-linked carboxymethyl xanthan gum tablet prepared by wet granulation technique.

PubMed

Maity, Siddhartha; Sa, Biswanath

2014-08-01

The objective of this work was to study the release behavior of prednisolone from calcium-cross-linked carboxymethyl xanthan gum (CMXG) tablets in dissolution medium having different pH values prevailing in the gastrointestinal lumen. Xanthan gum (XG) was derivatized to CMXG which was then cross-linked in situ with Ca(+2) ion during wet massing step of tablet preparation. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry studies did not show any drug-polymer interaction although the drug underwent solid-state transformation during compression as evident from X-ray diffraction analysis. In vitro release study demonstrated that increase in the amount of Ca(+2) ion decreased the drug release, and beyond a certain amount, the drug release increased. While increase in both drug load and tablet crushing strength decreased the drug release, increase in exposure time in acid solution of pH 1.2 increased the overall release of the drug. The mechanism of drug release was non-Fickian/anomalous. The results indicated that variation in the amount of Ca(+2) ion can modulate the drug release from CMXG matrix tablets as needed.

Evaluation of cellulose II powders as a potential multifunctional excipient in tablet formulations.

PubMed

de la Luz Reus Medina, Maria; Kumar, Vijay

2006-09-28

The use of UICEL-A/102 and UICEL-XL, the cellulose II powders, as a multifunctional direct compression excipient in the design of tablets containing hydrochlorothiazide (HCTZ) or ibuprofen (IBU), the model low and high dose drugs, respectively, has been reported. Commercial Oretic and Advil tablets containing HCTZ and IBU, respectively, and tablets made using Avicel PH-102 - the most commonly and widely used commercial direct compression excipient, were used in the study for comparison purposes. Tablets were made by first blending drug with the excipient and then with stearic acid, a lubricant, in a V-blender, followed by compressing into a tablet on a hydraulic press using 105 MPa of compression pressure and a dwell time of 30 s. The crushing strengths of HCTZ tablets decreased in the order Avicel PH-102>UICEL-XL, UICEL-A/102>Oretic and of IBU tablets in the order Avicel PH-102 > or = UICEL-XL approximately UICEL-A/102>Advil. The friability values for all tablets were well below the maximum 1% USP tolerance limit. UICEL-A/102 and UICEL-XL tablets containing HCTZ disintegrated rapidly (<25 s). Oretic tablets disintegrated in about 60 s, while Avicel PH-102 tablets remained intact during 1 h test period. The IBU tablets made using UICEL-A/102 disintegrated the fastest, UICEL-XL and Advil tablets the next, and Avicel PH-102 tablets remained intact. All tablets, except for those of Avicel PH-102, conformed to the USP drug release requirements. These results conclusively show that UICEL-A/102 and UICEL-XL have the potential to be used as filler, binder, and disintegrant, all-in-one, in the design of tablets containing either a low dose or high dose drug by the direct compression method.

21 CFR 520.2150a - Stanozolol tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

21 CFR 520.2150a - Stanozolol tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

21 CFR 520.2150a - Stanozolol tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

21 CFR 520.2150a - Stanozolol tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. The tablets may be crushed and administered...

Assessment of Clinical Practices for Crushing Medication in Geriatric Units.

PubMed

Fodil, M; Nghiem, D; Colas, M; Bourry, S; Poisson-Salomon, A-S; Rezigue, H; Trivalle, C

2017-01-01

To assess the modification of the form of medication and evaluate staff observance of good clinical practices. One-day assessment of clinical practices. 17 geriatrics units in the 3 Teaching Hospitals of Paris-Sud (APHP), France. Elderly in-patients with difficulties swallowing capsules and tablets. Assessment of target-patient prescriptions and direct observation of nurses' medical rounds. 155/526 in-patients (29.5%) were unable to swallow tablets or capsules: 98 (40.3%) in long-term care, 46 patients (23.8%) in the rehabilitation unit and 11 (12.2%) in the acute care unit (p = .005). In thirty-nine (27.3%) of the 143 prescriptions studied all tablets were safe to crush and all capsules were safe to open. In 104 cases, at least one medication could not be safely modified, including 26 cases (18.2%) in which none of the prescribed drugs were safe to crush or open. In 48.2% of the 110 medications that were crushed, crushing was forbidden, and presented a potential threat in 12.7% of cases or a reduced efficacy in 8.2% of cases. Crushing methods were rarely appropriate: no specific protective equipment was used (81.8%), crushing equipment was shared between patients without cleaning (95.1%), medications were spilled or lost (69.9%). The method of administration was appropriate (water, jellified water) in 25% of the cases, questionable (soup, coffee, compote, juice, cream) in 55% of the cases and unacceptable (laxative) in 21% of the cases. Management of drug prescriptions in patients with swallowing difficulties is not optimal, and may even have iatrogenic effects. In this study, 12.7% of the modifications of the drug form could have been harmful. Doctors, pharmacists and nurses need to reevaluate their practices.

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol.

PubMed

Obeidat, Wasfy M; Nokhodchi, Ali; Alkhatib, Hatim

2015-10-01

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.

Cinacalcet

MedlinePlus

Cinacalcet comes as a tablet to take by mouth. It is usually taken once a day with food or shortly after a meal. To help ... often than prescribed by your doctor.Swallow the tablets whole; do not split, chew, or crush them. ...

Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants

PubMed Central

Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel

2017-01-01

ABSTRACT Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences (P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.) PMID:29061746

Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants.

PubMed

Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel; Bassat, Quique

2018-01-01

Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences ( P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.). Copyright © 2017 Gargano et al.

Comparison of the In Vivo Pharmacokinetics and In Vitro Dissolution of Raltegravir in HIV Patients Receiving the Drug by Swallowing or by Chewing

PubMed Central

Baldelli, Sara; Cerea, Matteo; Landonio, Simona; Meraviglia, Paola; Simioni, Emanuela; Cozzi, Valeria; Fucile, Serena; Gazzaniga, Andrea; Clementi, Emilio; Galli, Massimo; Rizzardini, Giuliano; Gervasoni, Cristina

2012-01-01

The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interpatient/intrapatient variability. We investigated the potential contribution of the drug pharmaceutical formulation to RAL pharmacokinetics. We first compared in vivo the pharmacokinetics of RAL for 67 patients to whom the drug was administered by swallowing the intact tablet with those obtained from 13 HIV-infected patients who chewed the RAL tablet due to swallowing difficulties. Subsequently, we evaluated in vitro the dissolution of RAL tablets under different conditions. In the in vivo study, we found that patients given RAL by chewing the tablets presented pharmacokinetic profiles characterized by significantly higher RAL absorption than did patients receiving the drug by swallowing. The in vitro studies showed that when the whole tablets were exposed to an acidic medium, the release of RAL was very low, whereas when the tablets were crushed, the profiles presented significantly higher concentrations of RAL. Crushed tablets tested in water or in a pH 6.8 buffer exhibited prompt and complete dissolution of RAL. HIV-infected patients receiving RAL by chewing the tablet showed higher drug absorption and reduced pharmacokinetic variability compared with patients swallowing the intact tablet. This is related to problems in tablet disintegration and to erratic drug absorption. The amelioration of the RAL pharmaceutical formulation could improve drug pharmacokinetics. PMID:22964253

Voltammetric Studies of Zomepirac Sodium and Its Determination in Tablets by Differential-Pulse Polarography.

DTIC Science & Technology

1984-01-06

min in order to promote disintegration of the tablets . The remaining larger lumps of tablet mass were crushed with a glass rod and the mixture stirred...D-A136 982 VOLTAMMETRIC STUDIES OF ZOMEPIRAC SODIUM AND ITS i/i DETERMINATION IN TABLETS .. U) UTAH UNIV SALT LAKE CITY DEPT OF CHEMISTRY L G CHATTEN...TYPE OF REPORT &PEMOCVE Voltaninetric Studies of Zomepirac Sodium and its Dete~rmrination in Tablets by Differential-Pulse ,Technical Reportf 24 Pol

Adolescents' struggles with swallowing tablets: barriers, strategies and learning.

PubMed

Hansen, Dana Lee; Tulinius, Ditte; Hansen, Ebba Holme

2008-01-01

To explore adolescents' struggles with taking oral medications. Copenhagen, Denmark. Semi-structured qualitative interviews were conducted with 89 adolescents (33 boys, 56 girls) between the ages of 11 and 20. Adolescents were recruited through four public schools. To identify struggles with taking oral medication, interview transcripts were systematically searched for statements including the terms swallow, chew, crush and eat. Thematic analysis of the identified statements was carried out to reveal dominant themes in the adolescents' accounts. Over one-third of the adolescents spontaneously provided accounts of the difficulties they experienced with taking oral medications, especially with swallowing tablets. Three themes were dominant in their narratives: barriers, strategies and learning. Barriers experienced by the adolescents involved the medications' properties, e.g. taste. Adolescents developed strategies to overcome these barriers, e.g. crushing tablets. Via a process of learning-by-doing and the acquisition of increased experience and autonomy, many adolescents mastered the skill of swallowing tablets. Many adolescents experienced barriers in their attempts to swallow tablets. They developed various strategies to overcome these barriers and gradually mastered taking medicines in a learning-by-doing process.

Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

PubMed

Siden, Rivka; Wolf, Matthew

2013-06-01

The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in <20 mL of water: busulfan, cyclophosphamide 50 mg, dasatinib, imatinib, methotrexate, and thioguanine. For these drugs, drug-specific information pamphlets can be prepared for patient or caregiver use. Mercaptopurine, cyclophosphamide 25 mg, and mitotane tablets did not pass the disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

PubMed

Mishra, Saurabh M; Rohera, Bhagwan D

2017-11-01

The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: physicochemical and technological characterisation.

PubMed

Marinich, J A; Ferrero, C; Jiménez-Castellanos, M R

2009-05-01

Nowadays, graft copolymers are being used as an interesting option when developing a direct compression excipient for controlled release matrix tablets. New graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS) were synthesised by free radical polymerization and alternatively dried in a vacuum oven (OD) or freeze-dried (FD). This paper evaluates the performance of these new macromolecules and discusses the effect of the carbohydrate nature and drying process on their physicochemical and technological properties. Grafting of EMA on the carbohydrate backbone was confirmed by IR and NMR spectroscopy, and the grafting yields revealed that graft copolymers present mainly a hydrophobic character. The graft copolymerization also leads to more amorphous materials with larger particle size and lower apparent density and water content than carbohydrates (MS, MHS). All the products show a lack of flow, except MHSEMA derivatives. MSEMA copolymers underwent much plastic flow and less elastic recovery than MHSEMA copolymers. Concerning the effect of drying method, FD derivatives were characterised by higher plastic deformation and less elasticity than OD derivatives. Tablets obtained from graft copolymers showed higher crushing strength and disintegration time than tablets obtained from raw starches. This behaviour suggests that these copolymers could be used as excipients in matrix tablets obtained by direct compression and with a potential use in controlled release.

Influence of amorphous content on compaction behaviour of anhydrous alpha-lactose.

PubMed

Ziffels, S; Steckel, H

2010-03-15

Modified lactoses are widely used as filler-binders in direct compression of tablets. Until today, little about the compaction behaviour of anhydrous alpha-lactose is known. In this study, a new method to prepare anhydrous alpha-lactose from alpha-lactose monohydrate by desiccation with heated ethanol was evaluated and the influence of amorphous content in the lactose powder prior to modification on powder properties, compaction behaviour and storage stability was determined. The modification process led to anhydrous alpha-lactose with decreased bulk and tapped density, increased flow rate and significantly higher specific surface area. Due to the higher specific surface area, the compaction behaviour of the anhydrous alpha-lactose was found to be significantly better than the compaction behaviour of powder blends consisting of alpha-lactose monohydrate and amorphous lactose. An influence of the amorphous content prior to modification could be observed only at higher compaction forces. In general, tablets of modified powders needed longer time to disintegrate directly after compression. However, the storage stability of modified tablets was found to be better compared to the amorphous-crystalline tablets which were influenced by storage conditions, initial crushing strength as well as amorphous content due to the re-crystallization of amorphous lactose during storage. 2009 Elsevier B.V. All rights reserved.

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

PubMed

Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

2016-01-01

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.

Mechanical properties of acacia and eucalyptus wood chars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, M.; Verma, B.B.; Gupta, R.C.

1999-10-01

In the present investigation the effects of carbonization conditions (temperature and heating rate) on the mechanical properties (such as crushing and impact strengths and shatter index) of acacia and eucalyptus wood chars have been determined. The crushing and impact strengths of both the acacia and eucalyptus wood chars (made by slow carbonization) decreased with increase of preparation temperature up to 600 C, followed by an increase thereafter. These wood chars showed a continuous increase in shatter index values with carbonization temperature. In contrast to slow carbonization (heating rate 4 C min{sup {minus}1}), rapid carbonization (heating rate 30 C min{sup {minus}1})more » yielded chars of lower crushing strengths. Slowly carbonized eucalyptus wood gave chars of superior crushing and impact strengths than those produced from acacia wood under the same carbonization conditions. The crushing and impact strengths of these wood chars, in general, have shown an increase with increase in their apparent density. The crushing strength of cubic-shaped wood char decreased with increase in size.« less

Evaluation of validation of a fully instrumented Hüttlin HKC 05-TJ laboratory-scale fluidized bed granulator.

PubMed

Wöstheinrich, K; Schmidt, P C

2000-06-01

The instrumentation and validation of a laboratory-scale fluidized bed apparatus is described. For continuous control of the process, the apparatus is instrumented with sensors for temperature, relative humidity (RH), and air velocity. Conditions of inlet air, fluidizing air, product, and exhaust air were determined. The temperature sensors were calibrated at temperatures of 0.0 degree C and 99.9 degrees C. The calibration of the humidity sensors covered the range from 12% RH to 98% RH using saturated electrolyte solutions. The calibration of the anemometer took place in a wind tunnel at defined air velocities. The calibrations led to satisfying results concerning sensitivity and precision. To evaluate the reproducibility of the process, 15 granules were prepared under identical conditions. The influence of the type of pump used for delivering the granulating liquid was investigated. Particle size distribution, bulk density, and tapped density were determined. Granules were tableted on a rotary press at four different compression force levels, followed by determination of tablet properties such as weight, crushing strength, and disintegration time. The apparatus was found to produce granules with good reproducibility concerning the granule and tablet properties.

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation.

PubMed

Brouillet, F; Bataille, B; Cartilier, L

2008-05-22

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.

A randomized, open-label 3-way crossover study to investigate the relative bioavailability and bioequivalence of crushed sildenafil 20 mg tablets mixed with apple sauce, extemporaneously prepared suspension (EP), and intact sildenafil 20 mg tablets in healthy volunteers under fasting conditions.

PubMed

Gao, Xiang; Ndongo, Marie-Noella; Checchio, Tina M; Cook, Jack; Duncan, Barbara; LaBadie, Robert R

2015-01-01

The relative bioavailability and bioequivalence of 20-mg doses of a pediatric formulation of sildenafil extemporaneous preparation suspension (EP; 10 mg/mL), the sildenafil 20-mg intact tablet and the crushed sildenafil 20-mg tablet mixed with apple sauce were assessed in a single-dose, randomized, open-label, 3-way crossover study with 18 healthy adult volunteers. Blood samples were collected at predefined times and analyzed for sildenafil plasma concentrations. Natural log-transformed sildenafil pharmacokinetic parameters (Cmax , AUClast , and AUCinf ) were used to estimate relative bioavailability and construct 90% confidence intervals (CI) using a mixed-effects model. Bioequivalence was concluded among the three formulations with one exception, in which the EP suspension showed a 15% decrease in Cmax with a lower 90% CI of 76% compared with the intact tablet. The 15% decrease in sildenafil Cmax is not considered to be clinically relevant. Therefore, the EP suspension is considered to be an appropriate pediatric formulation. All 3 formulations were well tolerated in healthy adult volunteers. © 2014, The American College of Clinical Pharmacology.

Riveting in metal airplane construction. Part IV : strength of riveted joints in duralumin (concluded)

NASA Technical Reports Server (NTRS)

Pleines, Wilhelm

1930-01-01

Tests were made to determine the crushing strength of a riveted joint, in order to define the difference in crushing stregth between a strictly bolted joint and a riveted joint. The object was to tabulate the crushing strength by failure on various plate thicknesses for a one-rivet double-shear riveted joint.

Composition, Stability, and Bioavailability of Garlic Products Being Used in a Clinical Trial

PubMed Central

Lawson, Larry D.; Gardner, Christopher D.

2008-01-01

In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic and dried aged garlic extract) on serum lipids, the three garlic products have been characterized for (a) composition (14 sulfur and 2 non-sulfur compounds), (b) stability of suspected active compounds, and (c) availability of allyl thiosulfinates (mainly allicin) under both simulated gastrointestinal (tablet dissolution) conditions and in vivo. The allyl thiosulfinates of blended fresh garlic were stable for at least two years when stored at −80 °C. The dissolution release of thiosulfinates from the enteric-coated garlic tablets was found to be >95%. The bioavailability of allyl thiosulfinates from these tablets, measured as breath allyl methyl sulfide, was found to be complete and equivalent to that of crushed fresh garlic. S-allylcysteine was stable for 12 months at ambient temperature. The stability of the suspected active compounds under the conditions of the study and the bioavailability of allyl thiosulfinates from the dried garlic supplement have validated the use of these preparations for comparison in a clinical trial. PMID:16076102

Pharmacokinetics of nebulized terbinafine in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2012-09-01

Aspergillosis is one of the most difficult diseases to treat successfully in avian species. Terbinafine hydrochloride offers numerous potential benefits over traditionally used antifungals for treatment of this disease. Adding nebulized antifungals to treatment strategies is thought to improve clinical outcomes in lung diseases. To determine plasma concentrations of terbinafine after nebulization, 6 adult Hispaniolan Amazon parrots were randomly divided into 2 groups of 3. Each bird was nebulized for 15 minutes with 1 of 2 terbinafine solutions, one made with a crushed tablet and the second with raw drug powder. Blood samples were collected at baseline and at multiple time points up to 720 minutes after completing nebulization. Plasma and nebulization solutions were analyzed by high-performance liquid chromatography. The terbinafine concentration of the solution made with a crushed tablet (0.87 +/- 0.05 mg/mL) was significantly lower than was that made with raw powder (1.02 +/- 0.09 mg/mL). Plasma concentrations of terbinafine did not differ significantly between birds in the 2 groups. Plasma terbinafine concentrations in birds were maintained above in vitro minimum inhibitory concentrations for approximately 1 hour in birds nebulized with the crushed tablet solution and 4 hours in birds nebulized with the raw powder solution. Higher concentrations of solution, longer nebulization periods, or more frequent administration are likely needed to reach therapeutic plasma concentrations of terbinafine for clinically relevant periods in Hispaniolan Amazon parrots.

Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--Part II theophylline and cimetidine.

PubMed

Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

2009-05-01

The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease or Eudragit NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm(3) and size of 855 mum were quite close to Surelease-coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease-coated beads; 5.7 +/- 1.0 kP and 0.26 +/- 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease-coated theophylline beads released drug fastest overall (t(44.2%) = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease-coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease-coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.

Design space construction of multiple dose-strength tablets utilizing bayesian estimation based on one set of design-of-experiments.

PubMed

Maeda, Jin; Suzuki, Tatsuya; Takayama, Kozo

2012-01-01

Design spaces for multiple dose strengths of tablets were constructed using a Bayesian estimation method with one set of design of experiments (DoE) of only the highest dose-strength tablet. The lubricant blending process for theophylline tablets with dose strengths of 100, 50, and 25 mg is used as a model manufacturing process in order to construct design spaces. The DoE was conducted using various Froude numbers (X(1)) and blending times (X(2)) for theophylline 100-mg tablet. The response surfaces, design space, and their reliability of the compression rate of the powder mixture (Y(1)), tablet hardness (Y(2)), and dissolution rate (Y(3)) of the 100-mg tablet were calculated using multivariate spline interpolation, a bootstrap resampling technique, and self-organizing map clustering. Three experiments under an optimal condition and two experiments under other conditions were performed using 50- and 25-mg tablets, respectively. The response surfaces of the highest-strength tablet were corrected to those of the lower-strength tablets by Bayesian estimation using the manufacturing data of the lower-strength tablets. Experiments under three additional sets of conditions of lower-strength tablets showed that the corrected design space made it possible to predict the quality of lower-strength tablets more precisely than the design space of the highest-strength tablet. This approach is useful for constructing design spaces of tablets with multiple strengths.

Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

PubMed Central

Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

2014-01-01

The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation. PMID:24734053

Effects of hexagonal boron nitride on dry compression mixture of Avicel DG and Starch 1500.

PubMed

Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

2016-01-01

The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) on a (1:1) binary mixture of Avicel DG and Starch 1500 after using the dry granulation-slugging method and compare it with conventional lubricants, such as magnesium stearate (MGST), glyceryl behenate (COMP) and stearic acid (STAC). MGST is one of the most commonly used lubricants in the pharmaceutical industry. However, it has several adverse effects on tablet properties. In our current study, we employed various methods to eradicate the work hardening phenomenon in dry granulation, and used HBN as a new lubricant to overcome the adverse effects of other lubricants on tablet properties. HBN was found to be as effective as MGST and did not show any significant adverse effects on the crushing strength or work hardening. From the scanning electron microscope (SEM) images, it was concluded that HBN distributed better than MGST. As well as showing better distribution, HBN's effect on disintegration was the least pronounced. Semi-quantitative weight percent distribution of B and N elements in the tablets was obtained using EDS (energy dispersive spectroscopy). Based on atomic force microscope (AFM) surface roughness images, formulations prepared with 1% HBN showed better plastic character than those prepared with MGST.

Simulation of roller compaction with subsequent tableting and characterization of lactose and microcrystalline cellulose.

PubMed

Hein, Stephanie; Picker-Freyer, Katharina M; Langridge, John

2008-01-01

Tablets are by far the most common solid oral dosage forms, and many drugs need to be granulated before they can be tableted. Increasingly roller compaction is being used as a dry granulation technique; however it is a very time and material intensive method. Thus some mini roller compactors and simulations of the roller compaction process have been developed as a means of studying the technique at small scale. An important factor in the selection of materials for roller compaction is their ability to be recompressed into tablets after the initial roller compaction and milling steps. In this paper the roller compaction process was simulated on the basis of some models by Gereg and Cappola (2002) and Zinchuk et al. (2004). An eccentric tableting machine was used to make compacts from alpha-lactose monohydrate, anhydrous beta-lactose, spray-dried lactose and microcrystalline cellulose at different maximum relative densities (rho rel,max 0.6-0.9). These compacts were milled immediately to granules with a rotary granulator. The properties of the granules were analyzed and compared to the properties of the original powders. These granules and powders were then tableted at different maximum relative densities (rho rel,max 0.75-0.95) and their properties including elastic recovery, crushing force and 3D-model were analyzed. The properties of the tablets made from the granules were compared to the properties of the tablets made from the powders to determine which excipients are most suitable for the roller compaction process. The study showed that anhydrous beta-lactose is the preferred form of lactose for use in roller compaction since compaction did not affect tablet crushing force to a large extent. With the simulation of roller compaction process one is able to find qualified materials for use in roller compaction without the necessity of a great deal of material and time.

Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms.

PubMed

Duggan, Joan M; Akpanudo, Barbara; Shukla, Vipul; Gutterson, Glen; Eitniear, Lindsey; Sahloff, Eric G

2015-09-15

Evidence-based guidance is presented to assist clinicians in selecting alternative formulations of antiretroviral (ARV) agents for patients with human immunodeficiency virus (HIV) infection who are unable to swallow tablets or capsules. The inability to take medications in standard oral dosage forms can be associated with nonadherence or the use of alternative administration strategies such as capsule or tablet breaking, crushing, or chewing. Patients with HIV infection require long-term ARV therapy to maintain viral suppression; ARV agents are predominately available as tablets and capsules that may pose swallowing difficulties for some patients. Using a variety of sources (the primary literature, pharmaceutical package inserts, and requests for unpublished data from drug manufacturers), available evidence on the bioavailability of ARV medications after disruption of the capsule or tablet matrix was reviewed; information on alternative formulations of ARV agents was also assessed. With several ARV agents, disruption of the solid oral dosage form by crushing, chewing, or breaking tablets or opening capsules prior to ingestion has been shown to result in altered bioavailability or pharmacokinetics and thus the potential for incomplete virological suppression, increased adverse effects, and suboptimal health outcomes. Of the 33 single-agent ARV medications and combination ARV products in five classes available at the time of review, approximately half exist as powders, liquids, injectables, or chewable or dissolvable tablets. If alternative ARV formulations or administration methods are used, close monitoring for achievement of virological and immunologic success and potential toxicities is recommended. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Evaluation of the performance characteristics of bilayer tablets: Part II. Impact of environmental conditions on the strength of bilayer tablets.

PubMed

Kottala, Niranjan; Abebe, Admassu; Sprockel, Omar; Bergum, James; Nikfar, Faranak; Cuitiño, Alberto M

2012-12-01

Ambient air humidity and temperature are known to influence the mechanical strength of tablets. The objective of this work is to understand the influence of processing parameters and environmental conditions (humidity and temperature) on the strength of bilayer tablets. As part of this study, bilayer tablets were compressed with different layer ratios, dwell times, layer sequences, material properties (plastic and brittle), first and second layer forces, and lubricant concentrations. Compressed tablets were stored in stability chambers controlled at predetermined conditions (40C/45%RH, 40C/75%RH) for 1, 3, and 5 days. The axial strength of the stored tablets was measured and a statistical model was developed to determine the effects of the aforementioned factors on the strength of bilayer tablets. As part of this endeavor, a full 3 × 2(4) factorial design was executed. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina, USA). A model was fit using all the responses to determine the significant interactions (p < 0.05). Results of this study indicated that storage conditions and storage time have significant impact on the strength of bilayer tablets. For Avicel-lactose and lactose-Avicel tablets, tablet strength decreased with the increasing humidity and storage time. But for lactose-lactose tablets, due to the formation of solid bridges upon storage, an increase in tablet strength was observed. Significant interactions were observed between processing parameters and storage conditions on the strength of bilayer tablets.

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability.

PubMed

Solanki, Nayan G; Tahsin, Md; Shah, Ankita V; Serajuddin, Abu T M

2018-01-01

The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon ® VA64, Kollicoat ® IR, Affinsiol ™ 15 cP, and HPMCAS either individually or as binary blends (Kollidon ® VA64 + Affinisol ™ 15 cP, 1:1; Kollidon ® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon ® VA64-Affinisol ™ 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon ® VA64 and Affinisol ™ 15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users

PubMed Central

Harris, Stephen C; Perrino, Peter J; Smith, Ira; Shram, Megan J; Colucci, Salvatore V; Bartlett, Cynthia; Sellers, Edward M

2014-01-01

The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1–2 hours) versus OC and Oxy API (0.5–1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion. PMID:24243216

Treatment outcomes for tinea capitis in a skin of color population.

PubMed

Bhanusali, Dhaval; Coley, Marcelyn; Silverberg, Jonathan I; Alexis, Andrew; Silverberg, Nanette B

2012-07-01

Tinea capitis periodically undergoes demographic shifts in causative dermatophyte and therapeutic response to oral anti-fungal therapy. To determine prevalent fungal species and response to standard antifungal therapy in inner-city children of color. An IRB-approved chart review of demographic, clinical, diagnostic, and therapeutic data was conducted for children and young adults (0 to 18 years of age) who had scalp fungal culture performed for scalp hyperkeratosis and/or alopecia over a 2.5 year time-period. Supplemental parental phone interview was performed for missing data points. A total of 84 patients with final diagnosis of tinea capitis were identified-52% male, 60.6% African-American, 28.2% Hispanic, and 9.9% Caucasian. Complete resolution at 4 weeks was uncommon in all demographic groups (Hispanic: 11.7%, African-American: 41.3%). The Hispanic group and the youngest patients (aged less than 4 years) were less likely to respond to initial therapy, but the results were not significant. Of the 80 tinea capitis patients initially treated with griseofulvin, 41 out of 54 children (76%) had complete response to micronized suspension +/- crushed tablet (33% required shift to tablets from suspension) and 20 out of 26 (76.9%) cleared on crushed tablets alone. Of the 19 griseofulvin failures, 5 cleared on fluconazole suspension, 7 on terbinafine sprinkles, 3 on itraconazole therapy, and 4 were lost to follow-up. Of the 47 patients who could be evaluated long-term after a single course of oral griseofulvin at 6 weeks or greater, 38 had documented long-term mycological cure (80.8%) and 42 had long-term clinical cure (89%). Trichophyton tonsurans (n=40) was the most prevalent causative species identified on culture, followed by Alternaria species (n=10) and Microsporum canis (n=1). Retrospective chart review: patient population has a high rate of usage of over-the-counter antifungal creams and shampoos, affecting culture results. Tinea capitis is still the most common cause of Trichophyton tonsurans in New York City. Response rates to griseofulvin are similar to rates seen in the 1970s, but require higher dosing and conversion to crushed tablets in partial responders. Usage of crushed ultramicronized griseofulvin, terbinafine sprinkles, itraconazole, and fluconazole are alternative regimens for those children whose tinea capitis does not clear on griseofulvin suspension.

Ultrasound transmission measurements for tensile strength evaluation of tablets.

PubMed

Simonaho, Simo-Pekka; Takala, T Aleksi; Kuosmanen, Marko; Ketolainen, Jarkko

2011-05-16

Ultrasound transmission measurements were performed to evaluate the tensile strength of tablets. Tablets consisting of one ingredient were compressed from dibasic calcium phosphate dehydrate, two grades of microcrystalline cellulose and two grades of lactose monohydrate powders. From each powder, tablets with five different tensile strengths were directly compressed. Ultrasound transmission measurements were conducted on every tablet at frequencies of 2.25 MHz, 5 MHz and 10 MHz and the speed of sound was calculated from the acquired waveforms. The tensile strength of the tablets was determined using a diametrical mechanical testing machine and compared to the calculated speed of sound values. It was found that the speed of sound increased with the tensile strength for the tested excipients. There was a good correlation between the speed of sound and tensile strength. Moreover, based on the statistical tests, the groups with different tensile strengths can be differentiated from each other by measuring the speed of sound. Thus, the ultrasound transmission measurement technique is a potentially useful method for non-destructive and fast evaluation of the tensile strength of tablets. Copyright © 2011 Elsevier B.V. All rights reserved.

Embolic stroke associated with injection of buprenorphine tablets.

PubMed

Lim, C C Tchoyoson; Lee, Sze Haur; Wong, Yee-Choon; Hui, Francis

2009-09-15

Drug users who crush, dissolve, and inject buprenorphine tablets parenterally may be at risk of severe thromboembolic complications or death. We describe patients with neurologic complications after injecting buprenorphine tablets. Brain MRI including diffusion-weighted imaging (DWI) in patients admitted to the neurologic department after injecting buprenorphine tablets were reviewed. Seven men had neurologic complications after buprenorphine tablet injection. In 5 patients, multiple small scattered hyperintense lesions were detected on DWI in the cortex, white matter, and basal ganglia of the cerebral hemisphere; one patient had a single small lesion. The side of MRI abnormality corresponded to the side of needle marks on the neck except in one patient who had bilateral injections. One patient, who denied injecting into the neck, had DWI abnormalities in the middle cerebral artery territory on one side and occlusion of the ipsilateral internal carotid artery. Buprenorphine tablets can be intentionally or inadvertently injected into the carotid artery, causing a characteristic appearance on diffusion-weighted imaging, consistent with embolic cerebral infarction.

Tensile and shear methods for measuring strength of bilayer tablets.

PubMed

Chang, Shao-Yu; Li, Jian-Xin; Sun, Changquan Calvin

2017-05-15

Both shear and tensile measurement methods have been used to quantify interfacial bonding strength of bilayer tablets. The shear method is more convenient to perform, but reproducible strength data requires careful control of the placement of tablet and contact point for shear force application. Moreover, data obtained from the shear method depend on the orientation of the bilayer tablet. Although more time-consuming to perform, the tensile method yields data that are straightforward to interpret. Thus, the tensile method is preferred in fundamental bilayer tableting research to minimize ambiguity in data interpretation. Using both shear and tensile methods, we measured the mechanical strength of bilayer tablets made of several different layer combinations of lactose and microcrystalline cellulose. We observed a good correlation between strength obtained by the tensile method and carefully conducted shear method. This suggests that the shear method may be used for routine quality test of bilayer tablets during manufacturing because of its speed and convenience, provided a protocol for careful control of the placement of the tablet interface, tablet orientation, and blade is implemented. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-05-29

The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.

Efficacy and Safety of Praziquantel in Preschool-Aged Children in an Area Co-Endemic for Schistosoma mansoni and S. haematobium

PubMed Central

Coulibaly, Jean T.; N'Gbesso, Yve K.; Knopp, Stefanie; Keiser, Jennifer; N'Goran, Eliézer K.; Utzinger, Jürg

2012-01-01

Background In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied. Methodology We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians. Principal Findings Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children. Conclusions/Significance Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d'Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth. Trial Registration Controlled-Trials.com ISRCTN53172722 PMID:23236526

21 CFR 520.2345g - Tetracycline hydrochloride and sodium novobiocin tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... tablets. 520.2345g Section 520.2345g Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2345g Tetracycline hydrochloride and sodium novobiocin tablets. (a) Specifications. Each tablet... antibiotic per pound of body weight (one single-strength tablet for each 6 pounds or one triple-strength...

A critical Examination of the Phenomenon of Bonding Area - Bonding Strength Interplay in Powder Tableting.

PubMed

Osei-Yeboah, Frederick; Chang, Shao-Yu; Sun, Changquan Calvin

2016-05-01

Although the bonding area (BA) and bonding strength (BS) interplay is used to explain complex tableting behaviors, it has never been experimentally proven. The purpose of this study is to unambiguously establish the distinct contributions of each by decoupling the contributions from BA and BS. To modulate BA, a Soluplus® powder was compressed into tablets at different temperatures and then broken following equilibration at 25°C. To modulate BS, tablets were equilibrated at different temperatures. To simultaneously modulate BA and BS, both powder compression and tablet breaking test were carried out at different temperatures. Lower tablet tensile strength is observed when the powder is compressed at a lower temperature but broken at 25°C. This is consistent with the increased resistance to polymer deformation at lower temperatures. When equilibrated at different temperatures, the tensile strength of tablets prepared under identical conditions increases with decreasing storage temperature, indicating that BS is higher at a lower temperature. When powder compression and tablet breaking are carried out at the same temperature, the profile with a maximum tensile strength at 4°C is observed due to the BA-BS interplay. By systematically varying temperature during tablet compression and breaking, we have experimentally demonstrated the phenomenon of BA-BS interplay in tableting.

Comparison of breaking tests for the characterization of the interfacial strength of bilayer tablets.

PubMed

Castrati, Luca; Mazel, Vincent; Busignies, Virginie; Diarra, Harona; Rossi, Alessandra; Colombo, Paolo; Tchoreloff, Pierre

2016-11-20

The bilayer tableting technology is gaining more acceptance in the drug industry, due to its ability to improve the drug delivery strategies. It is currently assessed by the European Pharmacopoeia, that the mechanical strength of tablets can be evaluated using a diametral breaking tester. This device applies a force diametrically, and records the tablet breaking point. This approach has been used to measure the structural integrity of single layer tablets as well as bilayer (and multi-layer) tablets. The latter ones, however, have a much complex structure. Therefore, testing a bilayer tablet with the currently used breaking test methodology might not be appropriate. The aim of this work was to compare results from several tests that have been proposed to quantify the interfacial strength of bilayer tablets. The obtained results would provide an indication on which tests are appropriate to evaluate the robustness of a bilayer tablet. Bilayer tablets were fabricated using a model formulation: Microcrystalline Cellulose (MCC) for the first layer, and spray dried lactose (SDLac) as second layer. Each set of tablets were tested using the following tests: Diametral Test, Shear Test and Indentation Test. The tablets were examined before and after the breaking test using Scanning Electron Microscopy (SEM). When a bilayer tablet was subjected to shearing or indentation, it showed signs of clear delamination. Differently, using the diametral test system, the tablets showed no clear difference, before and after the testing. However, when examining each layer via SEM, it was clear that a fracture occurred in the layer made of SDLac. Thus, the diametral test is a measure of the strength of one of the two layers and therefore it is not suited to test the mechanical strength of bilayer tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

An index for evaluating difficulty of Chewing Index for chewable tablets.

PubMed

Gupta, Abhay; Chidambaram, Nallaperumal; Khan, Mansoor A

2015-02-01

Chewing difficulty index, a potential measure of difficulty in chewing the chewable tablets, has been described herein as the product of tablet thickness and tablet hardness measured under the diametral loading. The proposed index was evaluated by measuring the dimensions and mechanical strength of commercial and in-house prepared chewable tablets. Data collected on tablets with different thickness but same hardness or tensile strength suggests that the proposed index provides a good assessment of the force needed to chew the chewable tablets. Influence of brief exposure to salivary fluid during chewing on the mechanical strength of the chewable tablets was also evaluated. Thirty seconds exposure to the simulated salivary fluid was also found to significantly reduce (p < 0.05) the hardness and the chewing difficulty index of a number of evaluated chewable tablet drug products.

A material-sparing method for simultaneous determination of true density and powder compaction properties--aspartame as an example.

PubMed

Sun, Changquan Calvin

2006-12-01

True density results for a batch of commercial aspartame are highly variable when helium pycnometry is used. Alternatively, the true density of the problematic aspartame lot was obtained by fitting tablet density versus pressure data. The fitted true density was in excellent agreement with that predicted from single crystal structure. Tablet porosity was calculated from the true density and tablet apparent density. After making the necessary measurements for calculating tablet apparent density, the breaking force of each intact tablet was measured and tensile strength was calculated. With the knowledge of compaction pressure, tablet porosity and tensile strength, powder compaction properties were characterized using tabletability (tensile strength versus pressure), compactibility (tensile strength versus porosity), compressibility (porosity versus pressure) and Heckel analysis. Thus, a wealth of additional information on the compaction properties of the powder was obtained through little added work. A total of approximately 4 g of powder was used in this study. Depending on the size of tablet tooling, tablet thickness and true density, 2-10 g of powder would be sufficient for characterizing most pharmaceutical powders.

Effects of excipients and curing process on the abuse deterrent properties of directly compressed tablets.

PubMed

Rahman, Ziyaur; Zidan, Ahmed S; Korang-Yeboah, Maxwell; Yang, Yang; Siddiqui, Akhtar; Shakleya, Diaa; Khan, Mansoor A; Cruz, Celia; Ashraf, Muhammad

2017-01-30

The objective of the present investigation was to understand the effects of excipients and curing process on the abuse deterrent properties (ADP) of Polyox™ based directly compressible abuse deterrent tablet formulations (ADFs). The excipients investigated were lactose (monohydrate or anhydrous), microcrystalline cellulose and hydroxypropyl methylcellulose. The ADPs studied were tablet crush resistance or hardness, particle size distribution following mechanical manipulation, drug extraction in water and alcohol, syringeability and injectability. Other non-ADPs such as surface morphology and tablet dissolution were also studied. It was found that presence of 50% or more of water soluble or swellable excipient in the ADF tablets significantly affected the tablet hardness, particle size distribution following mechanical manipulation and drug extraction while small amount (5%) of excipients had either minimal or no effect on ADPs of these tablets. Addition of high molecular weight HPMC (K 100M) affected syringeability and injectability of ADF. Curing process was found to affect ADPs (hardness, particle size distribution, drug extraction and syringeability and injectability) when compared with uncured tablet. In conclusion, addition of large amount of excipients, especially water soluble ones in Polyox™ based ADF tablets increase the risk of abuse by various routes of administration. Published by Elsevier B.V.

Optimization of formulation and processing of Moringa oleifera and spirulina complex tablets.

PubMed

Zheng, Yi; Zhu, Fan; Lin, Dan; Wu, Jun; Zhou, Yichao; Mark, Bohn

2017-01-01

Objective: To prepare a more comprehensive nutrition, more balanced proportion of natural nutritional supplement tablets with Moringa oleifera leaves and spirulina the two nutrients which have complementary natural food ingredients. Method: On the basis of research M. oleifera leaves with spirulina nutrient composition was determined on M. oleifera leaves and spirulina ratio of raw materials, and the choice of microcrystalline cellulose, sodium salt of caboxy methyl cellulose(CMC),magnesium stearate excipient, through single factor and orthogonal experiment, selecting the best formula tablets prepared by powder direct compression technology, for preparation of M. oleifera and spirulina complex tablets. Results: The best ratio of raw material for the M. oleifera leaves powder: spirulina powder was 7:3, the best raw materials for the tablet formulation was 88.5%, 8.0% microcrystalline cellulose, CMC 2.0%, stearin magnesium 1.5%, the optimum parameters for the raw material crushing 200-300 mesh particle size, moisture content of 7%, tableting pressure 40 kN. Conclusion: Through formulation and process optimization, we can prepare more comprehensive and balanced nutrition M. oleifera and spirulina complex tablets, its sheet-shaped appearance, piece weight variation, hardness, friability, disintegration and other indicators have reached the appropriate quality requirements.

[Influence of polymer type on the physical properties and the release study of papaverine hydrochloride from tablets].

PubMed

Kasperek, Regina; Polski, Andrzej; Sobótka-Polska, Karolina; Poleszak, Ewa

2014-01-01

Polymers are widely used in drug manufacturing. Researchers studied their impact on the bioavailability of active substances or on physical properties of tablets for many years. To study the influence of polymer excipients, such as microcrystalline cellulose (Avicel PH 101, Avicel PH 102), croscarmellose sodium, crospovidone or polyvinylpyrrolidone, on the release profile of papaverine hydrochloride from tablets and on the physical properties of tablets. Six series of uncoated tablets were prepared by indirect method, with previous wet granulation. Tablets contained papaverine hydrochloride and various excipients. The physical properties of the prepared granules, tablets and the release profile of papaverine hydrochloride from tablets were examined. The content of papaverine hydrochloride from the release study were determined spectrophotometrically. All tablets met the pharmacopoeia requirements during following tests: the disintegration time of tablets, uncoated tablets resistance to abrasion, the weight uniformity and dose formulations, their dimensions, the resistance to crushing of tablets and the drug substance content in the tablet. In four cases more than 80% of papaverine was released up to 2 min, in one formula it was up to 5 min, and in last one up to 10 min. Tablets containing crospovidone disintegrated faster than tablets with croscarmellose sodium. Adding gelatinized starch to the tablet composition increased the disintegration time, hardness and delayed the release of papaverine. During the wet granulation process, granules containing polyvinylpyrrolidone were characterized by a suitable flow properties and slightly prolonged disintegration time. Tablets containing Avicel PH 102 compared to tablets with Avicel PH 101 had less weight loss during the test of mechanical resistance, improved hardness and faster release profile of papaverine from tablets.

Properties of concrete containing foamed concrete block waste as fine aggregate replacement

NASA Astrophysics Data System (ADS)

Muthusamy, K.; Budiea, A. M. A.; Zaidan, A. L. F.; Rasid, M. H.; Hazimmah, D. S.

2017-11-01

Environmental degradation due to excessive sand mining dumping at certain places and disposal of foamed concrete block waste from lightweight concrete producing industry are issues that should be resolved for a better and cleaner environment of the community. Thus, the main intention of this study is to investigate the potential of foamed concrete block waste as partial sand replacement in concrete production. The foamed concrete waste (FCW) used in this research that were supplied by a local lightweight concrete producing industry. The workability and compressive strength of concrete containing various percentage of foamed concrete waste as partial sand replacement has been investigated. Prior to the use, the foamed concrete waste were crushed to produce finer particles. Six concrete mixes containing various content of crushed foamed concrete waste that are 0%, 10%, 20%, 30%, 40% and 50% were used in this experimental work. Then the prepared specimens were placed in water curing until the testing age. Compressive strength test and flexural strength tests were conducted at 7, 14 and 28 days. The result shows that integration of crushed foamed concrete waste as partial sand replacement in concrete reduces the mix workability. It is interesting to note that both compressive strength and flexural strength of concrete improves when 30% crushed foamed concrete waste is added as partial sand replacement.

Compaction behaviour and mechanical strength of lactose-sodium starch glycolate and lactose-croscarmellose sodium binary tablets

NASA Astrophysics Data System (ADS)

Ashikin Yaakub, Nur; Shamsul Anuar, Mohd; Tahir, Suraya Mohd

2018-04-01

The focus of this study is to elucidate the effects of adding super disintegrants (SSG and Acdisol) to a filler (lactose) in terms of the compaction behaviour and mechanical strength of the formed binary tablets. The tablets were formed in a uniaxial die compaction process with compaction pressures ranging from 37.7MPa to 150.7 MPa. Consequently, the findings indicated that the increasing of the compaction pressure and the percentage mass composition of the super disintegrants would led to the increased in the strength of the tablets as well as their plastic energies, where this was more apparent for the case of the binary lactose/Acdisol tablets. In addition, as the compaction pressure increased, the maximum ejection pressure required to eject the tablet from the die cavity also increased. In contrast, a decreased in the maximum ejection pressure was observed as the composition of both super disintegrants increased in the lactose-super disintegrant binary tablets. In conclusion, the addition of super disintegrant; SSG with lactose and Acdisol with lactose; would enhanced the mechanical strength of lactose based tablets especially for the case of acdisol-lactose binary tablets in the experimental conditions adopted in this current work.

Assessment of intra-granular and extra-granular fracture in the development of tablet tensile strength.

PubMed

Mitra, Biplob; Hilden, Jon; Litster, James D

2018-05-24

When a tablet is compacted from deformable granules and then broken, the fracture plane may cleave granules in two (intra-granular fracture) or separate neighboring granules (extra-granular fracture). In this study, a novel method was developed to quantify the extent of intra- versus extra-granular fracture by compacting tablets from multi-colored ideal granules and evaluating fracture surfaces. The proportions of intra-granular and extra-granular fracture were quantified and modeled in light of a new metric, the deformation potential, Δ, reflecting the solid fraction increase as an initial granule bed is compressed into a final tablet. Results show that a measurable tablet strength is achieved at Δ > 0.18, but intra-granular fracture is not observed until Δ > 0.21. At very large Δ, tablets experience almost exclusively intra-granular fracture, yet the tablet tensile strength is considerably lower than that of a tablet compacted from raw powders versus pre-compacted granules. Thus, secondary compaction of granules appears to weaken the granule matrix, leading to reduced tablet tensile strength even in the presence of strong extra-granular bonding. Copyright © 2018. Published by Elsevier Inc.

Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.

PubMed

Niwa, Masahiro; Hiraishi, Yasuhiro

2014-01-30

Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

Toward predicting tensile strength of pharmaceutical tablets by ultrasound measurement in continuous manufacturing.

PubMed

Razavi, Sonia M; Callegari, Gerardo; Drazer, German; Cuitiño, Alberto M

2016-06-30

An ultrasound measurement system was employed as a non-destructive method to evaluate its reliability in predicting the tensile strength of tablets and investigate the benefits of incorporating it in a continuous line, manufacturing solid dosage forms. Tablets containing lactose, acetaminophen, and magnesium stearate were manufactured continuously and in batches. The effect of two processing parameters, compaction force and level of shear strain were examined. Young's modulus and tensile strength of tablets were obtained by ultrasound and diametrical mechanical testing, respectively. It was found that as the blend was exposed to increasing levels of shear strain, the speed of sound in the tablets decreased and the tablets became both softer and mechanically weaker. Moreover, the results indicate that two separate tablet material properties (e.g., relative density and Young's modulus) are necessary in order to predict tensile strength. A strategy for hardness prediction is proposed that uses the existing models for Young's modulus and tensile strength of porous materials. Ultrasound testing was found to be very sensitive in differentiating tablets with similar formulation but produced under different processing conditions (e.g., different level of shear strain), thus, providing a fast, and non-destructive method for hardness prediction that could be incorporated to a continuous manufacturing process. Copyright © 2016 Elsevier B.V. All rights reserved.

Fused deposition modeling provides solution for magnetic resonance imaging of solid dosage form by advancing design quickly from prototype to final product.

PubMed

Charest, Ken; Mak-Jurkauskas, Melody L; Cinicola, Daniel; Clausen, Andrew M

2013-02-01

The release profile of active pharmaceutical ingredient (API) from its solid dosage form is an important aspect of drug development as it is often used to predict potential drug release characteristics of a product in vivo. In recent years, magnetic resonance imaging has emerged as a nondestructive technique that captures the physical changes of solid dosage forms during dissolution. An example that highlights this application is in the dissolution of modified-release tablet studies. As the tablet dissolves, API disperses in a hydrogel matrix within the tablet, and swelling of the hydrogel layer eventually leads to release of API over time. To achieve optimum signal-to-noise ratios, the tablet should be placed in the most homogeneous region of the magnet and remain there throughout the dissolution experiment. Moreover, the tablet holder must maintain the tablet position without interfering with the natural dissolution process, such as by crushing the softened tablet. This can be difficult because the size, shape, and rigidity of the tablet change during dissolution. This article describes the process, material, and manufacture of a novel device that meets these challenges, with emphasis on how additive manufacturing on a 3D printer enabled an efficient and inexpensive process of design improvements.

How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Microhardness of ribbons and mercury porosimetry measurements of tablets.

PubMed

Freitag, Franziska; Reincke, Katrin; Runge, Jürgen; Grellmann, Wolfgang; Kleinebudde, Peter

2004-07-01

The effect of roll compaction/dry granulation on the ribbon and tablet properties produced using different magnesium carbonates was evaluated. The ribbon microhardness and the pore size distribution of tablets were used as evaluation factors. Increasing the specific compaction force resulted in higher microhardness for ribbons prepared with all four magnesium carbonates accompanied with decreased part of fine. Consequently, the corresponding produced tablets displayed a lower tensile strength. A possible correlation between the particle shape, surface area and the resulting pore structure of tablets produced with the four different types of magnesium carbonate was observed. The tensile strength of tablets prepared using granules was lower than tensile strength of tablets produced using starting materials. The partial loss of compactibility resulted in a demand of low loads during roll compaction. However, the impact of changes in the material properties during the roll compaction depended greatly on the type of magnesium carbonate, the specific compaction force and the tableting pressure applied.

Methods for the practical determination of the mechanical strength of tablets--from empiricism to science.

PubMed

Podczeck, Fridrun

2012-10-15

This review aims to awake an interest in the determination of the tensile strength of tablets of various shapes using a variety of direct and indirect test methods. The United States Pharmacopoeia monograph 1217 (USP35/NF30, 2011) has provided a very good approach to the experimental determination of and standards for the mechanical strength of tablets. Building on this monograph, it is hoped that the detailed account of the various methods provided in this review will encourage industrial and academic scientists involved in the development and manufacture of tablet formulations to take a step forward and determine the tensile strength of tablets, even if these are not simply flat disc-shaped or rectangular. To date there are a considerable number of valid test configurations and stress equations available, catering for many of the various shapes of tablets on the market. The determination of the tensile strength of tablets should hence replace the sole determination of a breaking force, because tensile strength values are more comparable and suggestions for minimum and/or maximum values are available. The review also identifies the gaps that require urgent filling. There is also a need for further analysis using, for example, Finite Element Method, to provide correct stress solutions for tablets of differing shapes, but this also requires practical experiments to find the best loading conditions, and theoretical stress solutions should be verified with practical experiments. Copyright © 2012 Elsevier B.V. All rights reserved.

General and mechanistic optimal relationships for tensile strength of doubly convex tablets under diametrical compression.

PubMed

Razavi, Sonia M; Gonzalez, Marcial; Cuitiño, Alberto M

2015-04-30

We propose a general framework for determining optimal relationships for tensile strength of doubly convex tablets under diametrical compression. This approach is based on the observation that tensile strength is directly proportional to the breaking force and inversely proportional to a non-linear function of geometric parameters and materials properties. This generalization reduces to the analytical expression commonly used for flat faced tablets, i.e., Hertz solution, and to the empirical relationship currently used in the pharmaceutical industry for convex-faced tablets, i.e., Pitt's equation. Under proper parametrization, optimal tensile strength relationship can be determined from experimental results by minimizing a figure of merit of choice. This optimization is performed under the first-order approximation that a flat faced tablet and a doubly curved tablet have the same tensile strength if they have the same relative density and are made of the same powder, under equivalent manufacturing conditions. Furthermore, we provide a set of recommendations and best practices for assessing the performance of optimal tensile strength relationships in general. Based on these guidelines, we identify two new models, namely the general and mechanistic models, which are effective and predictive alternatives to the tensile strength relationship currently used in the pharmaceutical industry. Copyright © 2015 Elsevier B.V. All rights reserved.

[The effects of various factors on the in vitro velocity of drug release from repository tablets. Part 4: Isoniazid (Rimicid) respository tablets (author's transl)].

PubMed

Tomassini, L; Michailova, D; Naplatanova, D; Slavtschev, P

1979-12-01

The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.

Understanding the Delamination Risk of a Trilayer Tablet Using Minipiloting Tools.

PubMed

Tao, Jing; Robertson-Lavalle, Sophia; Pandey, Preetanshu; Badawy, Sherif

2017-11-01

A multilayer tablet is one of the formulation options used to mitigate chemical and physical incompatibility between different drug substances. Feasibility studies of multilayer tablets are often conducted using round flat-faced punch tooling. However, the link between different tooling designs and multilayer tablet performance is not well established. This study uses a prototype trilayer tablet and examines tooling design considerations when conducting small-scale studies to gauge the risk of interfacial defects. The impact of tablet weight and dimensions was evaluated to gain understanding of the effect of scale-up/down of tablet size. The factors in tooling selection, including tablet shape, cup depth, and size of embossing were evaluated to gain insight on the impact of tooling design on the interfacial strength of the trilayer tablet. It was found that tablet weight and dimensions can significantly affect the interfacial strength due to their impact on force transmission during compression and the retardation force from the die wall during ejection. Round flat-faced tooling generated trilayer tablets of the strongest interfacial strength compared to typical commercial tablets-oval shaped with concave surfaces. These factors should be accounted for when using round flat compacts to assess the interface risks of a multilayer tablet. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Systematic evaluation of common lubricants for optimal use in tablet formulation.

PubMed

Paul, Shubhajit; Sun, Changquan Calvin

2018-05-30

As an essential formulation component for large-scale tablet manufacturing, the lubricant preserves tooling by reducing die-wall friction. Unfortunately, lubrication also often results in adverse effects on tablet characteristics, such as prolonged disintegration, slowed dissolution, and reduced mechanical strength. Therefore, the choice of lubricant and its optimal concentration in a tablet formulation is a critical decision in tablet formulation development to attain low die-wall friction while minimizing negative impact on other tablet properties. Three commercially available tablet lubricants, i.e., magnesium stearate, sodium stearyl fumerate, and stearic acid, were systematically investigated in both plastic and brittle matrices to elucidate their effects on reducing die-wall friction, tablet strength, tablet hardness, tablet friability, and tablet disintegration kinetics. Clear understanding of the lubrication efficiency of commonly used lubricants as well as their impact on tablet characteristics would help future tablet formulation efforts. Copyright © 2018 Elsevier B.V. All rights reserved.

Formulation and development of tablets based on Ludipress and scale-up from laboratory to production scale.

PubMed

Heinz, R; Wolf, H; Schuchmann, H; End, L; Kolter, K

2000-05-01

In spite of the wealth of experience available in the pharmaceutical industry, tablet formulations are still largely developed on an empirical basis, and the scale-up from laboratory to production is a time-consuming and costly process. Using Ludipress greatly simplifies formulation development and the manufacturing process because only the active ingredient Ludipress and a lubricant need to be mixed briefly before being compressed into tablets. The studies described here were designed to investigate the scale-up of Ludipress-based formulations from laboratory to production scale, and to predict changes in tablet properties due to changes in format, compaction pressure, and the use of different tablet presses. It was found that the tensile strength of tablets made of Ludipress increased linearly with compaction pressures up to 300 MPa. It was also independent of the geometry of the tablets (diameter, thickness, shape). It is therefore possible to give an equation with which the compaction pressure required to achieve a given hardness can be calculated for a given tablet form. The equation has to be modified slightly to convert from a single-punch press to a rotary tableting machine. Tablets produced in the rotary machine at the same pressure have a slightly higher tensile strength. The rate of increase in pressure, and therefore the throughput, has no effect on the tensile strength of Ludipress tablets. It is thought that a certain minimum dwell time is responsible for this difference. The production of tablets based on Ludipress can be scaled up from one rotary press to another without problem if the powder mixtures are prepared with the same mixing energy. The tensile strength curve determined for tablets made with Ludipress alone can also be applied to tablets with a small quantity (< 10%) of an active ingredient.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hallerman, G.; Gray, R.J.

An instrument for crushing-strength determinations of uncoated and pyrolytic-carbon-coated fuel particles (50 to 500 mu in diameter) was developed to relate the crushing strength of the particles to their fabricability. The instrument consists of a loading mechanism, load cell, and a power supply-readout unit. The information that can be obtained by statistical methods of the data analysis is illustrated by results on two batches of fuel particles. (auth)

Improving Powder Tableting Performance through Materials Engineering

NASA Astrophysics Data System (ADS)

Osei-Yeboah, Frederick

Adequate mechanical strength is a critical requirement to the successful development of a tablet product. Before tablet compression, powders are often engineered by various processes including wet granulation and surface coating, which may improve or adversely affect the powder tableting performance. Such effects, commonly, result from a change in either particle mechanical properties or particulate (size, shape) properties. In this work, tableting performance is interpreted based on the qualitative bonding-area and bonding-strength (BABS) model. The tabletability of the microcrystalline cellulose (MCC) granules deteriorates rapidly with increasing amount of granulating water and eventually leads to over-granulation at high water level. Granule surface smoothing, size enlargement, granule densification and shape rounding are the dominant factors leading to the tabletability reduction of plastic MCC. Incorporation of increasing amounts of brittle excipients, such as lactose or dibasic calcium phosphate reduces the rate of tabletability reduction by promoting more granule fragmentation, introducing more surface area available for bonding. When a sufficient amount of brittle excipients is used, the over-granulation phenomenon can be eliminated. Surface coating of incompressible MCC pellets with highly bonding polymer leads to sufficient surface deformation and adhesion to enable direct compression of the pellets into tablets of adequate mechanical strength. This improvement is enhanced by the presence of moisture, which plasticizes the polymer to allow the development of a larger bonding area between coated pellets. The relationship between mechanical properties and tableting behavior is systematically investigated in polymeric composites using celecoxib-polyvinylpyrrolidone vinyl acetate solid dispersions. Mechanical properties such as indentation hardness of the solid dispersions were measured using nanoindentation. Incorporation of celecoxib up to 60% by weight hardens the polymers, which reduces bonding area but increases bonding strength. On the other hand, moisture softens the solid dispersions and facilitates deformation under pressure to improve tablet mechanical strength. In summary, insights into the deteriorated tabletability of wet granulated powders have been developed and strategies for improving tabletability have been demonstrated. Also, the relationship between particle mechanical properties and tableting performance has been examined using solid dispersions. The BABS model has been further developed to enable its widespread application in interpreting complex tableting behavior.

In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations.

PubMed

Mayock, Stephen P; Saim, Said; Fleming, Alison B

2017-12-01

Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone DETERx (Xtampza ® ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography. Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid. Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.

Usage of Crushed Concrete Fines in Decorative Concrete

NASA Astrophysics Data System (ADS)

Pilipenko, Anton; Bazhenova, Sofia

2017-10-01

The article is devoted to the questions of usage of crushed concrete fines from concrete scrap for the production of high-quality decorative composite materials based on mixed binder. The main problem in the application of crushed concrete in the manufacture of decorative concrete products is extremely low decorative properties of crushed concrete fines itself, as well as concrete products based on them. However, crushed concrete fines could have a positive impact on the structure of the concrete matrix and could improve the environmental and economic characteristics of the concrete products. Dust fraction of crushed concrete fines contains non-hydrated cement grains, which can be opened in screening process due to the low strength of the contact zone between the hydrated and non-hydrated cement. In addition, the screening process could increase activity of the crushed concrete fines, so it can be used as a fine aggregate and filler for concrete mixes. Previous studies have shown that the effect of the usage of the crushed concrete fines is small and does not allow to obtain concrete products with high strength. However, it is possible to improve the efficiency of the crushed concrete fines as a filler due to the complex of measures prior to mixing. Such measures may include a preliminary mechanochemical activation of the binder (cement binder, iron oxide pigment, silica fume and crushed concrete fines), as well as the usage of polycarboxylate superplasticizers. The development of specific surface area of activated crushed concrete fines ensures strong adhesion between grains of binder and filler during the formation of cement stone matrix. The particle size distribution of the crushed concrete fines could achieve the densest structure of cement stone matrix and improve its resistance to environmental effects. The authors examined the mechanisms of structure of concrete products with crushed concrete fines as a filler. The results of studies of the properties of the crushed concrete fines were provided. It is shown that the admixture of the crushed concrete fines has little effect on the colour characteristics of the decorative concrete products. The preferred options to improve the surfaces of decorative concrete are also proposed.

Formulation and characterization of cetylpyridinium chloride bioadhesive tablets.

PubMed

Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Kelidari, Hamidreza; Lashkari, Maryam

2014-12-01

Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent. CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured. The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M. The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength.

Effect of surface energy on powder compactibility.

PubMed

Fichtner, Frauke; Mahlin, Denny; Welch, Ken; Gaisford, Simon; Alderborn, Göran

2008-12-01

The influence of surface energy on the compactibility of lactose particles has been investigated. Three powders were prepared by spray drying lactose solutions without or with low proportions of the surfactant polysorbate 80. Various powder and tablet characterisation procedures were applied. The surface energy of the powders was characterized by Inverse Gas Chromatography and the compressibility of the powders was described by the relationship between tablet porosity and compression pressure. The compactibility of the powders was analyzed by studying the evolution of tablet tensile strength with increasing compaction pressure and porosity. All powders were amorphous and similar in particle size, shape, and surface area. The compressibility of the powders and the microstructure of the formed tablets were equal. However, the compactibility and dispersive surface energy was dependent of the composition of the powders. The decrease in tablet strength correlated to the decrease in powder surface energy at constant tablet porosities. This supports the idea that tablet strength is controlled by formation of intermolecular forces over the areas of contact between the particles and that the strength of these bonding forces is controlled by surface energy which, in turn, can be altered by the presence of surfactants.

Predicting the tensile strength of compacted multi-component mixtures of pharmaceutical powders.

PubMed

Wu, Chuan-Yu; Best, Serena M; Bentham, A Craig; Hancock, Bruno C; Bonfield, William

2006-08-01

Pharmaceutical tablets are generally produced by compacting a mixture of several ingredients, including active drugs and excipients. It is of practical importance if the properties of such tablets can be predicted on the basis of the ones for constituent components. The purpose of this work is to develop a theoretical model which can predict the tensile strength of compacted multi-component pharmaceutical mixtures. The model was derived on the basis of the Ryshkewitch-Duckworth equation that was originally proposed for porous materials. The required input parameters for the model are the relative density or solid fraction (ratio of the volume of solid materials to the total volume of the tablets) of the multi-component tablets and parameters associated with the constituent single-component powders, which are readily accessible. The tensile strength of tablets made of various powder blends at different relative density was also measured using diametrical compression. It has been shown that the tensile strength of the multi-component powder compacts is primarily a function of the solid fraction. Excellent agreement between prediction and experimental data for tablets of binary, ternary and four-component blends of some widely used pharmaceutical excipients was obtained. It has been demonstrated that the proposed model can well predict the tensile strength of multi-component pharmaceutical tablets. Thus, the model will be a useful design tool for formulation engineers in the pharmaceutical industry.

On the Post-Compaction Evolution of Tensile Strength of Sodium Chloride-Starch Mixture Tablets.

PubMed

Radojevic, Jovana; Zavaliangos, Antonios

2017-08-01

This study focuses on the evolution of mechanical behavior of starch and sodium chloride (NaCl) mixture tablets after compaction. This type of mixture has attracted attention in the past because such tablets exhibit lower tensile strengths than the ones of its individual components. Here we demonstrate that the strengths of NaCl-starch mixtures and NaCl tablets evolve after compaction in an opposite way. When stored at relative humidity of 60%, NaCl tablets strengthen with time, whereas NaCl-starch mixtures weaken. To explain this behavior, we propose that in the NaCl-starch mixture, the presence of 2 materials with significantly different elastic moduli leads to creation of tensile stresses at the stiffer NaCl-NaCl contacts. Such tensile stresses lead to a reduction in strength of the compacted mixtures by negating a local dissolution-reprecipitation mechanism, which strengthens the NaCl-NaCl in pure NaCl tablet. This effect is proven by experimental results from NaCl specimens diametrically loaded during storage. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Composition and process for making an insulating refractory material

DOEpatents

Pearson, Alan; Swansiger, Thomas G.

1998-04-28

A composition and process for making an insulating refractory material. The composition includes calcined alumina powder, flash activated alumina powder, an organic polymeric binder and a liquid vehicle which is preferably water. Starch or modified starch may also be added. A preferred insulating refractory material made with the composition has a density of about 2.4-2.6 g/cm.sup.3 with reduced thermal conductivity, compared with tabular alumina. Of importance, the formulation has good abrasion resistance and crush strength during intermediate processing (commercial sintering) to attain full strength and refractoriness, good abrasion resistance and crush strength.

Gluten and Aluminum Content in Synthroid® (Levothyroxine Sodium Tablets).

PubMed

Espaillat, Ramon; Jarvis, Michael F; Torkelson, Cory; Sinclair, Brent

2017-07-01

Inquiries from healthcare providers and patients about the gluten and aluminum content of Synthroid ® (levothyroxine sodium tablets) have increased. The objective of this study was to measure and evaluate the gluten content of the raw materials used in the manufacturing of Synthroid. Additionally, this study determined the aluminum content in different strengths of Synthroid tablets by estimating the amount of aluminum in the raw materials used in the manufacturing of Synthroid. Gluten levels of three lots of the active pharmaceutical ingredient (API) and one lot of each excipient from different vendors were examined. The ingredients in all current Synthroid formulations (strengths) were evaluated for their quantity of aluminum. Gluten concentrations were below the lowest limit of detection (<3.0 ppm) for all tested lots of the API and excipients of Synthroid tablets. Aluminum content varied across tablet strengths (range 19-137 µg/tablet). Gluten levels of the API and excipients were found to be below the lowest level of detection and are considered gluten-free based on the US Food and Drug Administration (FDA) definition for food products. Across the various tablet strengths of Synthroid, the maximum aluminum levels were well below the FDA-determined minimal risk level for chronic oral aluminum exposure (1 mg/kg/day). These data demonstrate that Synthroid tablets are not a source for dietary gluten and are a minimal source of aluminum. AbbVie Inc.

Effect of diboron trioxide on the crushing strength and smelting mechanism of high-chromium vanadium-titanium magnetite pellets

NASA Astrophysics Data System (ADS)

Cheng, Gong-jin; Gao, Zi-xian; Yang, He; Xue, Xiang-xin

2017-11-01

The effect of diboron trioxide (B2O3) on the crushing strength and smelting mechanism of high-chromium vanadium-titanium magnetite pellets was investigated in this work. The main characterization methods were X-ray fluorescence, inductively coupled plasma-atomic emission spectroscopy, mercury injection porosimetry, X-ray diffraction, metallographic microscopy, and scanning electron microscopy-energy-dispersive X-ray spectroscopy. The results showed that the crushing strength increased greatly with increasing B2O3 content and that the increase in crushing strength was strongly correlated with a decrease in porosity, the formation of liquid phases, and the growth and recrystallization consolidation of hematite crystalline grains. The smelting properties were measured under simulated blast furnace conditions; the results showed that the smelting properties within a certain B2O3 content range were improved and optimized except in the softening stage. The valuable element B was easily transformed to the slag, and this phenomenon became increasingly evident with increasing B2O3 content. The formation of Ti(C,N) was mostly avoided, and the slag and melted iron were separated well during smelting with the addition of B2O3. The size increase of the melted iron was consistent with the gradual optimization of the dripping characteristics with increasing B2O3 content.

Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

NASA Astrophysics Data System (ADS)

Juban, Audrey; Briançon, Stéphanie; Puel, François; Hoc, Thierry; Nouguier-Lehon, Cécile

2017-06-01

In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

Limited Influence of Excipients in Extemporaneous Compounded Suspensions

PubMed Central

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Marro, Diego; Uriel, Marta

2017-01-01

Objective: The objective of this study was to identify whether compounding oral suspensions with SyrSpend SF based on tablets or capsules is a suitable alternative for using raw pharmaceutical materials. Methods: Suspensions based on 5 different tablets and capsules were studied in SyrSpend SF. The summary of product characteristics of these different tablets and capsules were obtained from the manufacturer. Our hypothesis was that, if the maximum beyond-use date of the study was reached, the excipient did not seem to have an influence on the stability of the active pharmaceutical ingredient (API) within the studied time frame. Results: All excipients used in flecainide acetate, labetalol HCl, and tiagabine HCl tablets as well as in celecoxib and oseltamivir capsules did not seem to influence the beyond-use date of the overall suspension based on SyrSpend SF. Conclusion: Although using raw materials as API sources is preferred, oral suspensions with SyrSpend SF prepared from crushed tablets or opened capsules could be a possible alternative. Based on this study, a wide range of different excipients does not seem to impact the beyond-use date of different APIs compounded in SyrSpend SF. PMID:29276267

Limited Influence of Excipients in Extemporaneous Compounded Suspensions.

PubMed

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Marro, Diego; Uriel, Marta

2017-06-01

Objective: The objective of this study was to identify whether compounding oral suspensions with SyrSpend SF based on tablets or capsules is a suitable alternative for using raw pharmaceutical materials. Methods: Suspensions based on 5 different tablets and capsules were studied in SyrSpend SF. The summary of product characteristics of these different tablets and capsules were obtained from the manufacturer. Our hypothesis was that, if the maximum beyond-use date of the study was reached, the excipient did not seem to have an influence on the stability of the active pharmaceutical ingredient (API) within the studied time frame. Results: All excipients used in flecainide acetate, labetalol HCl, and tiagabine HCl tablets as well as in celecoxib and oseltamivir capsules did not seem to influence the beyond-use date of the overall suspension based on SyrSpend SF. Conclusion: Although using raw materials as API sources is preferred, oral suspensions with SyrSpend SF prepared from crushed tablets or opened capsules could be a possible alternative. Based on this study, a wide range of different excipients does not seem to impact the beyond-use date of different APIs compounded in SyrSpend SF.

Effect of repeated compaction of tablets on tablet properties and work of compaction using an instrumented laboratory tablet press.

PubMed

Gamlen, Michael John Desmond; Martini, Luigi G; Al Obaidy, Kais G

2015-01-01

The repeated compaction of Avicel PH101, dicalcium phosphate dihydrate (DCP) powder, 50:50 DCP/Avicel PH101 and Starch 1500 was studied using an instrumented laboratory tablet press which measures upper punch force, punch displacement and ejection force and operates using a V-shaped compression profile. The measurement of work compaction was demonstrated, and the test materials were ranked in order of compaction behaviour Avicel PH101 > DCP/Avicel PH101 > Starch > DCP. The behaviour of the DCP/Avicel PH101 mixture was distinctly non-linear compared with the pure components. Repeated compaction and precompression had no effect on the tensile fracture strength of Avicel PH101 tablets, although small effects on friability and disintegration time were seen. Repeated compaction and precompression reduced the tensile strength and the increased disintegration time of the DCP tablets, but improved the strength and friability of Starch 1500 tablets. Based on the data reported, routine laboratory measurement of tablet work of compaction may have potential as a critical quality attribute of a powder blend for compression. The instrumented press was suitable for student use with minimal supervisor input.

Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection.

PubMed

Weiner, Marc; Savic, Radojka M; Kenzie, William R Mac; Wing, Diane; Peloquin, Charles A; Engle, Melissa; Bliven, Erin; Prihoda, Thomas J; Gelfond, Jonathan A L; Scott, Nigel A; Abdel-Rahman, Susan M; Kearns, Gregory L; Burman, William J; Sterling, Timothy R; Villarino, M Elsa

2014-06-01

In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults. Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentration-time curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME). There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all ≥18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed. A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society 2014. This work is written by US Government employees and is in the public domain in the US.

Stability of an extemporaneous alcohol-free melatonin suspension.

PubMed

Johnson, Cary E; Cober, Mary Petrea; Thome, Tennille; Rouse, Emily

2011-03-01

The stability of alcohol-free oral suspensions of melatonin 1 mg/mL, extemporaneously prepared from two commercially available melatonin tablet products, was studied. Four 1-mg/mL melatonin suspensions were prepared. Formulations A and B contained 20 crushed 3-mg tablets of melatonin combined with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF to produce a volume of 60 mL. Formulations C and D were prepared by crushing 20 combination tablets containing melatonin 3 mg and pyridoxine hydrochloride 10 mg and then combining the powder with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF to produce a 60-mL volume. The suspensions were prepared in triplicate and stored at room temperature in amber plastic prescription bottles. Immediately after preparation and on days 7, 15, 30, 60, and 90, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography (HPLC). The samples were also evaluated for any changes in color, odor, and taste. HPLC analysis demonstrated that at least 94% of the initial melatonin concentration in formulations A and B, and at least 98% of that in formulations C and D, remained throughout the 90-day study period. Detectable changes in color, odor, or taste occurred in all of the formulations. Extemporaneously prepared, alcohol-free, 1-mg/mL suspensions of melatonin and melatonin-pyridoxine hydrochloride in a 1:1 mixture of Ora-Plus and either Ora Sweet or Ora Sweet SF were stable for at least 90 days when stored in 2-oz amber plastic bottles at room temperature.

Naratriptan hydrochloride in extemporaneosly compounded oral suspensions.

PubMed

Zhang, Y P; Trissel, L A; Fox, J L

2000-01-01

The purpose of this study was to determine the pharmaceutical acceptability and chemical stability of naratriptan hydrochloride in three extemporaneously compounded suspension formulations. The naratriptan-hydrochloride oral suspensions were prepared from 2.5-mg commercial tablets yielding a nominal naratriptan concentration of 0.5 mg/mL. The suspension vehicles selected for testing were Syrpalta, an equal-parts mixture of Ora-Plus and Ora-Sweet, and an equal-parts mixture of Ora-Plus and Ora-Sweet SF. The tablets were crushed and thoroughly triturated to a fine powder using a porcelain mortar and pestle. The powder was incorporated into a portion of the Syrpalta or Ora-Plus suspension vehicle and mixed until homogeneous. The mixtures were then brought to volume with Syrpalta, Ora-Sweet or Ora-Sweet SF, as appropriate. The suspensions were packaged in amber, plastic, screw-cap prescription bottles and stored at 23 deg C for seven days and 4 deg C for 90 days. An adequate suspension was never achieved in Syrpalta. The crushed-tablet powder did not produce a uniformly dispersed mixture and exhibited clumping and a high rate of sedimentation. A distinct layer of the solid tablet material settled immediately after shaking. Over the next four hours, a densely packed, yellow, caked layer formed at the bottom of the containers, making resuspension difficult. During storage, the caking became worse. Chemical analysis was not performed. The Ora-Plus and Ora-Sweet or Ora-Sweet SF suspensions had a slight greenish cast and were resuspended without difficulty by shaking for approximately ten seconds, yielding easily poured and homogeneous mixtures throughout the study. Visible settling and layering did not begin for four hours with the Ora-Sweet suspension and 24 hours for the Ora-Sweet SF suspension. High pressure liquid chromatographic analysis found that the naratriptan concentration in both suspension-vehicle combinations exhibited little or no loss for seven days at 23 deg C and 90 days at 4 deg C. At least 96% of the inital concentration remained at all time points. Naratriptan hydrochloride extemporaneously prepared as oral suspensions from tablets in equal-parts mixtures of Ora-Plus suspension vehicle with Ora-Sweet and with Ora-Sweet SF syrups was pharmaceutically acceptable and chemically stable for at least seven days at 23 deg C and 90 days at 4 deg C. Syrpalta was unacceptable for use as a vehicle for naratriptan hydrochloride suspensions prepared from tablets.

DEVELOPMENT OF A CALCIUM-BASED SORBENT FOR HOT GAS CLEANUP

DOE Office of Scientific and Technical Information (OSTI.GOV)

T.D. Wheelock; L.K. Doraiswamy; K. Constant

1999-10-01

The development and testing of potential calcium-based sorbents for hot gas cleanup continued. One of the most promising materials combines powdered limestone and a calcium aluminate cement by two step pelletization followed by steam curing. Reasonably strong pellets are produced with good adsorption characteristics by incorporating 20 wt.% cement in the core and 40 wt.% cement in the shell. The resulting 4.76 mm diameter pellets are capable of withstanding a crushing force approaching 11.5 N/mm before breaking and are also capable of removing H{sub 2}S from dilute, hot gas streams. The pellets are also regenerable and reusable. Another promising materialmore » combines calcium carbonate powder and finely ground calcined alumina in tablet form. The small tablets are prepared by mixing the materials with water to form a thick paste which is then molded and dried. The tablets are hardened by calcining at either 1000 to 1100 C. The resulting tablets are strong and capable of removing H{sub 2}S from a dilute, hot gas stream.« less

Preparation and stability evaluation of extemporaneous oral suspension of valsartan using commercially available tablets.

PubMed

Zaid, Abdel Naser; Assali, Mohyeddin; Qaddomi, Aiman; Ghanem, Mashhour; Zaaror, Yara Abu

2014-01-01

The aim of this study was to develop an extemporaneous valsartan suspension (80 mg valsartan/5 mL) starting from commercial tablets (80-mg/ tablet). A high-performance liquid chromatographic system was used for the analysis and quantification of valsartan in the samples studied. Samples of valsartan suspension for analysis were prepared as reported by the validated high-performance liquid chromatographic method and the dissolution tests were performed according to the U.S. Food and Drug Administration's method. The high-performance liquid chromatographic assay indicated that the 80-mg/5-mL valsartan suspension was stable for 30 days when stored at long-term and accelerated storage conditions. Valsartan release profile showed that approximately 85% of valsartan dissolved after 10 minutes and, accordingly, the calculation of similarity factor was not necessary. It is possible for the pharmacist to crush valsartan 80-mg tablets and prepare a suspension which has dosage flexibility that can be calculated according to body-surface area, kidney, and liver functions, without affecting the chemical stability of the active ingredient nor its dissolution profile and also have a cost-effective dosage form.

A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride.

PubMed

Mužíková, Jitka; Kubíčková, Alena

2016-09-01

The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders.

Stability of extemporaneous erlotinib, lapatinib, and imatinib oral suspensions.

PubMed

Li, Quan; Liu, Zhaoying; Kolli, Shamalatha; Wetz, Karen; Griffith, Niesha; Poi, Ming J

2016-09-01

The stability of extemporaneously prepared erlotinib, lapatinib, and imatinib oral liquid dosage forms using two commercially available vehicles when stored at 4 and 25 °C was evaluated. Three batches of extemporaneous oral suspensions were prepared for each drug. Erlotinib and lapatinib tablets were crushed and mixed in a 1:1 mixture of Ora-Plus:Ora-Sweet solution to yield 10- and 50-mg/mL suspensions, respectively. Imatinib tablets were crushed and mixed in Ora-Sweet solution to yield a 40-mg/mL suspension. Suspensions were stored in amber plastic bottles, and samples from each bottle were obtained on days 0, 1, 3, 7, 14, and 28. Erlotinib 10-mg/mL and lapatinib 50-mg/mL oral suspensions in a 1:1 mixture of Ora-Plus and Ora-Sweet retained at least 90% of their initial concentration throughout the 28-day study when stored at 25 °C. Visual inspection revealed notable viscosity changes in the erlotinib and lapatinib suspensions stored at 4 °C for 7 days and beyond. The viscosity of these preparations increased with time and was particularly evident with the erlotinib suspension, which exhibited a puddinglike texture. Imatinib 40-mg/mL oral suspension in Ora-Sweet appeared stable for up to 14 days when stored at both 25 and 4 °C. Erlotinib 10-mg/mL and lapatinib 50-mg/mL oral suspensions prepared from commercially available tablets were stable for at least 28 days when prepared in a 1:1 mixture of Ora-Plus:Ora-Sweet at 25 °C. Imatinib 40-mg/mL oral suspension prepared from commercially available tablets was stable for up to 14 days when prepared in Ora-Sweet and stored at 25 and 4 °C. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Axial strength test for round flat faced versus capsule shaped bilayer tablets.

PubMed

Franck, Jason; Abebe, Admassu; Keluskar, Rekha; Martin, Kyle; Majumdar, Antara; Kottala, Niranjan; Stamato, Howard

2015-03-01

There has been increasing interest in fixed dose combination (FDC) therapy. Multi-layer tablets are a popular choice among various technologies to deliver FDCs. In most cases, round flat faced tooling is used in testing tablets as they have the simplest geometry. However, shaped tooling is more common for commercial products and may have an effect on bilayer tablet strength. Capsule shaped bilayer tablets, similar to a commercial image, and holders conforming to the tablet topology, were compared with similar round flat faced bilayer tablets and their corresponding holders. Bilayer tablets were subjected to an axial test device, until fracture and the quantitative breaking force value was recorded. As the second layer compression force increases, regardless of holder design, an increase in breaking force occurs as expected. This consistent trend provides insight regarding the breaking force of capsule shaped bilayer tablets. The results of this study show that at lower second layer compression forces, tablet geometry does not significantly impact the results. However, at higher compression forces, a significant difference in breaking force between tablet geometries exists. Therefore, using a test geometry close to the final commercial tablet image is recommended to have the most accurate prediction for tablet breakage.

Self-organizing map analysis using multivariate data from theophylline tablets predicted by a thin-plate spline interpolation.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Yamamoto, Rie; Takayama, Kozo

2013-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and a design space. We integrated thin-plate spline (TPS) interpolation and Kohonen's self-organizing map (SOM) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared based on a standard formulation. The tensile strength, disintegration time, and stability of these variables were measured as response variables. These responses were predicted quantitatively based on nonlinear TPS. A large amount of data on these tablets was generated and classified into several clusters using an SOM. The experimental values of the responses were predicted with high accuracy, and the data generated for the tablets were classified into several distinct clusters. The SOM feature map allowed us to analyze the global and local correlations between causal factors and tablet characteristics. The results of this study suggest that increasing the proportion of microcrystalline cellulose (MCC) improved the tensile strength and the stability of tensile strength of these theophylline tablets. In addition, the proportion of MCC has an optimum value for disintegration time and stability of disintegration. Increasing the proportion of magnesium stearate extended disintegration time. Increasing the compression force improved tensile strength, but degraded the stability of disintegration. This technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulations.

An Evaluation of the Binding Strength of Okra Gum and the Drug Release Characteristics of Tablets Prepared from It.

PubMed

Hussain, Amjad; Qureshi, Farah; Abbas, Nasir; Arshad, Muhammad Sohail; Ali, Ejaz

2017-06-02

The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was determined quantitatively. Additionally, naproxen sodium tablets were prepared by using okra gum as a binder and were evaluated for their properties including hardness, friability, disintegration time, and dissolution rate. The binding strength values were compared with that of pre-gelatinized starch, a commonly used tablet binder. The results from universal testing machine indicate that the binding strengths of all dispersions of okra increase as the concentration increases from 1% to 5% and ranges from 2.5 to 4.5 N, which are almost twice a high as those of pre-gelatinized starch. The tablets prepared with okra gum have shown good mechanical strength with hardness values of 7-8.5 kg/cm² and a friability <1%, comparable to tablets prepared with starch. The disintegration time was longer (7.50 min with okra gum and 5.05 min with starch paste), and the drug release from these tablets was slower than the formulations with starch. The higher binding ability of okra gum probably linked with its chemical composition as it mainly contains galactose, rhamnose, and galacturonic acid. This study concludes that okra gum is a better binder than pre-gelatinized starch, it might be explored in future for introduction as a cost-effective binder in the pharmaceutical industry.

A case study of chewed Truvada® for PrEP maintaining protective drug levels as measured by a novel urine tenofovir assay.

PubMed

Lalley-Chareczko, Linden; Clark, Devon; Zuppa, Athena F; Moorthy, Ganesh; Conyngham, Caitlin; Mounzer, Karam; Koenig, Helen

2017-01-01

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada ® ) given as pre-exposure prophylaxis (PrEP) successfully blocks HIV when taken once daily prior to potential HIV exposure. A 22-year-old male reported difficulty swallowing FTC/TDF for PrEP and subsequently began chewing the FTC/TDF tablets. Monthly urine samples assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated tenofovir levels >1,000 ng/ml, indicative of protection from HIV acquisition, over a 48-week period. Data from observational studies of HIV-positive patients details the successful treatment of HIV using crushed FTC/TDF delivered via feeding and gastronomy tubes while small, randomized trials of healthy volunteers demonstrate bioequivalence between whole and crushed FTC/TDF.

Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-06-10

The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. Copyright © 2018 Elsevier B.V. All rights reserved.

A study of a co-processed dry binder composed of microcrystalline cellulose and glycerol monostearate.

PubMed

Mužíková, Jitka; Muchová, Sandra

2012-10-01

The paper studies the co-processed dry binder LubriToseTM MCC from the viewpoint of energy evaluation of the compression process, strength and disintegration time of tablets. The results were compared with the identical evaluation of physical mixtures of microcrystalline cellulose with several types of lubricants. LubriTose MCC showed the lowest value of energy for friction, the highest value of energy accumulated by the tablet, and the highest plasticity of all tableting materials under study. There were no marked differences in the values of the energy of decompression. The tensile strength of tablets from LubriTose MCC was lower than in those from the mixture of Vivapur® 12 and glycerol monostearate, in the compression forces of 4 and 5 kN it was comparable with the tensile strength of tablets from Vivapur 12 with Poloxamer 407. Disintegration time of tablets from LubriTose MCC was shorter than that of those from Vivapur 12 with glycerol monostearate at the compression force of 3 kN, in the case of the compression forces of 4 and 5 kN no statistically significant difference was found between the values of these tableting materials.

A new tablet brittleness index.

PubMed

Gong, Xingchu; Sun, Changquan Calvin

2015-06-01

Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of properties of tablets and energy profile of compaction of two spray-dried lactoses.

PubMed

Muzíková, Jitka; Sináglová, Pavla

2013-01-01

The paper compared two spray-dried lactoses Flowlac 100 and SuperTab 14SD from the standpoint of tensile strength and disintegration time of tablets, the effect of an addition of the lubricant magnesium stearate and silicified microcrystalline cellulose on these properties, and also from the standpoint of the energy profile of compression. The comparison of the values was performed at the compression force of 15 kN. The strength of tablets was higher in the case of SuperTab 14SD, an increase in the concentration of magnesium stearate did not decrease tablet strength. Prosolv SMCC 90 increased the strength of tablets and made it equal for both lactoses, but it also increased the sensitivity to the added lubricant. The disintegration time of tablets was shorter in the case of SuperTab 14SD, an increased concentration of magnesium stearate prolonged it, and an addition of Prosolv SMCC 90 shortened it and made it equal for both lactoses. From the energy standpoint, the maximal energy was higher in the case of SuperTab 14SD, an addition of Prosolv SMCC 90 increased it and again made it equal for both lactoses. The differences in the values of the maximal energy were primarily due to the values of the energy for friction and the energy accumulated by the tablet after compression, and there was no marked difference in the values of the energy of decompression. SuperTab 14SD showed a higher plasticity than Flowlac 100.

Structural investigation of spherical hollow excipient Mannit Q by X-ray microtomography.

PubMed

Kajihara, Ryusuke; Noguchi, Shuji; Iwao, Yasunori; Yasuda, Yuki; Segawa, Megumi; Itai, Shigeru

2015-11-10

The structure of Mannit Q particles, an excipient made by spray-drying a d-mannitol solution, and Mannit Q tablets were investigated by synchrotron X-ray microtomography. The Mannit Q particles had a spherical shape with a hollow core. The shells of the particles consisted of fine needle-shaped crystals, and columnar crystals were present in the hollows. These structural features suggested the following formation mechanism for the hollow particles:during the spray-drying process, the solvent rapidly evaporated from the droplet surface, resulting in the formation of shells made of fine needle-shaped crystals.Solvent remaining inside the shells then evaporated slowly and larger columnar crystals grew as the hollows formed. Although most of the Mannit Q particles were crushed on tableting, some of the particles retained their hollow structures, probably because the columnar crystals inside the hollows functioned as props. This demonstrated that the tablets with porous void spaces may be readily manufactured using Mannit Q. Copyright © 2015 Elsevier B.V. All rights reserved.

Phenomena of Foamed Concrete under Rolling of Aircraft Wheels

NASA Astrophysics Data System (ADS)

Jiang, Chun-shui; Yao, Hong-yu; Xiao, Xian-bo; Kong, Xiang-jun; Shi, Ya-jie

2014-04-01

Engineered Material Arresting System (EMAS) is an effective technique to reduce hazards associated with aircraft overrunning runway. In order to ascertain phenomena of the foamed concrete used for EMAS under rolling of aircraft wheel, a specially designed experimental setup was built which employed Boeing 737 aircraft wheels bearing actual vertical loads to roll through the foamed concrete. A number of experiments were conducted upon this setup. It is discovered that the wheel rolls the concrete in a pure rolling manner and crushes the concrete downwards, instead of crushing it forward, as long as the concrete is not higher than the wheel axle. The concrete is compressed into powder in-situ by the wheel and then is brought to bottom of the wheel. The powder under the wheel is loose and thus is not able to sustain wheel braking. It is also found that after being rolled by the wheel the concrete exhibits either of two states, i.e. either 'crushed through' whole thickness of the concrete or 'crushed halfway', depending on combination of strength of the concrete, thickness of the concrete, vertical load the wheel carries, tire dimension and tire pressure. A new EMAS design concept is developed that if an EMAS design results in the 'crushed through' state for the main gears while the 'crushed halfway' state for the nose gear, the arresting bed would be optimal to accommodate the large difference in strength between the nose gear and the main gear of an aircraft.

Studies for understanding effects of additions on the strength of cement concrete

NASA Astrophysics Data System (ADS)

Bucur, R. D.; Barbuta, M.; Konvalina, P.; Serbanoiu, A. A.; Bernas, J.

2017-09-01

The paper analyzes the effects of different types of additions introduced in concrete mix on the compressive strength. The current studies show that additions contribute to improve some characteristics of concrete and to reduce the cement dosage, so it can obtain concretes which are cheaper and friendlier with environment. In the experimental mixes were introduced: crushed natural aggregates, slag aggregates, silica fume, fly ash, chopped tire, polystyrene granule, glass fibers and metallic fibers. The experimental values of compressive strengths were compared for two concrete grades (C20/25 and C25/30). The study shown that near the well-known possibilities of improving mechanical strengths of cement concrete by increasing cement dosage and strength, by using crushed aggregates and by reducing the water/cement ratio, there are other methods in which less cement is used by replacing it with different wastes or by adding fiber.

Laterality and grip strength influence hand bone micro-architecture in modern humans, an HRpQCT study.

PubMed

Reina, Nicolas; Cavaignac, Etienne; Trousdale, William H; Laffosse, Jean-Michel; Braga, José

2017-06-01

It is widely hypothesized that mechanical loading, specifically repetitive low-intensity tasks, influences the inner structure of cancellous bone. As such, there is likely a relationship between handedness and bone morphology. The aim of this study is to determine patterns in trabecular bone between dominant and non-dominant hands in modern humans. Seventeen healthy patients between 22 and 32 years old were included in the study. Radial carpal bones (lunate, capitate, scaphoid, trapezium, trapezoid, 1st, 2nd and 3rd metacarpals) were analyzed with high-resolution micro-computed tomography. Additionally, crush and pinch grip were recorded. Factorial analysis indicated that bone volume ratio, trabeculae number (Tb.N), bone surface to volume ratio (BS.BV), body weight, stature and crush grip were all positively correlated with principal components 1 and 2 explaining 78.7% of the variance. Volumetric and trabecular endostructural parameters (BV/TV, BS/BV or Tb.Th, Tb.N) explain the observed inter-individual variability better than anthropometric or clinical parameters. Factors analysis regressions showed correlations between these parameters and the dominant side for crush strength for the lunate (r 2 = 0.640, P < 0.0001), trapezium (r 2 = 0.836, P < 0.0001) and third metacarpal (r 2 = 0.763). However, despite a significant lateralization in grip strength for all patients, the endostructural variability between dominant and non-dominant sides was limited in perspective to inter-individual differences. In conclusion, handedness is unlikely to generate trabecular patterns of asymmetry. It appears, however, that crush strength can be considered for endostructural analysis in the modern human wrist. © 2017 Anatomical Society.

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability.

PubMed

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (P app ) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f 1 ) and similarity (f 2 ) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating P app and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in C max and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f 1 and f 2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption.

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

PubMed Central

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f1 and f2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption. PMID:28352156

Influence of disintegrants in different substrate physical form on dimensional recovery of multi-component tablet.

PubMed

Sarkar, Srimanta; Ooi, Shing Ming; Liew, Celine Valeria; Tan, Bing Xun; Heng, Paul Wan Sia

2014-11-20

This study investigated the influence of different disintegrants, present in different substrate physical forms, on dimensional recovery of multi-component tablets prepared at different compression pressures. Formulations containing model drug, metformin, (10%, w/w), different disintegrants (10%, w/w), and lactose (80%, w/w) were compressed directly or after granulation using polyvinyl pyrrolidone (1%, w/w) as binder, into tablets (350 mg, 10mm diameter) at 150, 200, and 250 N/mm(2) compression pressures. Tablets were characterized for immediate dimensional recovery (IR) after ejection from the die, latent dimensional recovery (LR) over 24 h, tensile strength, and disintegration. The IR was predominantly contributed by crystalline components whereas LR was brought about by polymeric materials. With increased compression pressure, higher degree of plastic deformation of the polymeric disintegrants resulted in tablet with lower LR and higher tensile strength. Presence of polyvinyl pyrrolidone in the granules contributed considerably to plastic deformation, and the tablets produced had lower LR, higher tensile strength, and longer disintegration time. This study indicated that use of granules as the feed substrate physical form and a prudent selection of components may enable the coating of resultant tablets immediately after compression without the risk of coat damage due to LR. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist

PubMed Central

Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

2012-01-01

Purpose: The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Materials and Methods: Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 23 full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Results: Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug–excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. Conclusion: It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease. PMID:23580933

Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist.

PubMed

Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

2012-10-01

The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 2(3) full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug-excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease.

Near-infrared chemical imaging (NIR-CI) as a process monitoring solution for a production line of roll compaction and tableting.

PubMed

Khorasani, Milad; Amigo, José M; Sun, Changquan Calvin; Bertelsen, Poul; Rantanen, Jukka

2015-06-01

In the present study the application of near-infrared chemical imaging (NIR-CI) supported by chemometric modeling as non-destructive tool for monitoring and assessing the roller compaction and tableting processes was investigated. Based on preliminary risk-assessment, discussion with experts and current work from the literature the critical process parameter (roll pressure and roll speed) and critical quality attributes (ribbon porosity, granule size, amount of fines, tablet tensile strength) were identified and a design space was established. Five experimental runs with different process settings were carried out which revealed intermediates (ribbons, granules) and final products (tablets) with different properties. Principal component analysis (PCA) based model of NIR images was applied to map the ribbon porosity distribution. The ribbon porosity distribution gained from the PCA based NIR-CI was used to develop predictive models for granule size fractions. Predictive methods with acceptable R(2) values could be used to predict the granule particle size. Partial least squares regression (PLS-R) based model of the NIR-CI was used to map and predict the chemical distribution and content of active compound for both roller compacted ribbons and corresponding tablets. In order to select the optimal process, setting the standard deviation of tablet tensile strength and tablet weight for each tablet batch was considered. Strong linear correlation between tablet tensile strength and amount of fines and granule size was established, respectively. These approaches are considered to have a potentially large impact on quality monitoring and control of continuously operating manufacturing lines, such as roller compaction and tableting processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of poly(vinyl acetate) based floating matrix tablets.

PubMed

Strübing, Sandra; Metz, Hendrik; Mäder, Karsten

2008-03-03

Floating Kollidon SR matrix tablets containing Propranolol HCl were developed and characterized with respect to drug release characteristics and floating strength. Kollidon SR was able to delay Propranolol HCl release efficiently. Drug release kinetics was evaluated using the Korsmeyer-Peppas model and found to be governed by Fickian diffusion. Tablet floating started immediately and continued for 24 h. It was possible to monitor the floating strength of the matrix devices using a simple experimental setup. Floating strength was related to Kollidon SR level with improved floating characteristics for samples with a high polymer/drug ratio. Swelling characteristics of the tablets were analyzed by applying the equation according to Therien-Aubin et al. The influence of the polymer content on swelling characteristics was found to be only marginal. Furthermore, the new method of benchtop MRI was introduced to study the water diffusion and swelling behaviour non-invasively and continuously.

Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain.

PubMed

Hussain, Amjad; Syed, Muhammad Ali; Abbas, Nasir; Hanif, Sana; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Hussain, Khalid; Akhlaq, Muhammad; Ahmad, Zeeshan

2016-06-01

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

Simplified formulations with high drug loads for continuous twin-screw granulation.

PubMed

Meier, R; Thommes, M; Rasenack, N; Krumme, M; Moll, K-P; Kleinebudde, P

2015-12-30

As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities. Copyright © 2015 Elsevier B.V. All rights reserved.

A study of a novel coprocessed dry binder composed of α-lactose monohydrate, microcrystalline cellulose and corn starch.

PubMed

Mužíková, Jitka; Srbová, Alena; Svačinová, Petra

2017-12-01

This paper deals with a study of the novel coprocessed dry binder Combilac®, which contains 70% of α-lactose monohydrate, 20% of microcrystalline cellulose and 10% of native corn starch. These tests include flow properties, compressibility, lubricant sensitivity, tensile strength and disintegration time of tablets. Compressibility is evaluated by means of the energy profile of compression process, test of stress relaxation and tablet strength. The above-mentioned parameters are also evaluated in the physical mixture of α-lactose monohydrate, microcrystalline cellulose and native corn starch and compared with Combilac. Combilac shows much better flowability than the physical mixture of the used dry binders. Its compressibility is better, tablets possess a higher tensile strength. Neither Combilac, nor the physical mixture can be compressed without lubricants due to high friction and sticking to the matrix. Combilac has a higher lubricant sensitivity than the physical mixture of the dry binders. Disintegration time of Combilac tablets is comparable with the disintegration time of tablets made from the physical mixture.

Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal tablets prepared by direct compression.

PubMed

Ikeuchi-Takahashi, Yuri; Ishihara, Chizuko; Onishi, Hiraku

2017-09-01

The purpose of the present work was to evaluate polyvinyl alcohols (PVAs) as a mucoadhesive polymer for mucoadhesive buccal tablets prepared by direct compression. Various polymerization degree and particle diameter PVAs were investigated for their usability. The tensile strength, in vitro adhesive force, and water absorption properties of the tablets were determined to compare the various PVAs. The highest values of the tensile strength and the in vitro adhesive force were observed for PVAs with a medium viscosity and small particle size. The optimal PVA was identified by a factorial design analysis. Mucoadhesive tablets containing the optimal PVA were compared with carboxyvinyl polymer and hydroxypropyl cellulose formulations. The optimal PVA gives a high adhesive force, has a low viscosity, and resulted in relatively rapid drug release. Formulations containing carboxyvinyl polymer had high tensile strengths but short disintegration times. Higher hydroxypropyl cellulose concentration formulations had good adhesion forces and very long disintegration times. We identified the optimal characteristics of PVA, and the usefulness of mucoadhesive buccal tablets containing this PVA was suggested from their formulation properties.

Improvement of physicomechanical properties of carbamazepine by recrystallization at different pH values.

PubMed

Javadzadeh, Yousef; Mohammadi, Ameneh; Khoei, Nazaninossadat Seyed; Nokhodchi, Ali

2009-06-01

The morphology of crystals has an appreciable impact role on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviours of drugs. The objective of this study was to achieve an improved physicomechanical property of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution rate was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressure and measuring their hardness. SEM studies showed that the carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle shape. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature during recrystallization procedure or pH of crystallization media. The crushing strength of tablets indicated that all of the recrystallized carbamazepine samples had better compactiblity than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate for carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.

Tableting properties of silica aerogel and other silicates.

PubMed

Hentzschel, C M; Alnaief, M; Smirnova, I; Sakmann, A; Leopold, C S

2012-04-01

In solid oral dosage forms silicates are commonly used as glidants in low concentration. However, due to their large specific surface area, silicates may also be used as carrier materials for drugs. Moreover, silicates allow amorphisation of drugs by co-grinding or processing with supercritical fluids. The aim of this study was to investigate the physical and the tableting properties of Silica Aerogel (special type of silica with an extremely large specific surface area), Neusilin(®) US2 (magnesium aluminometasilicate), Florite(®) (calcium silicate) and Aerosil(®) 200 (colloidal silica). Powder blends of Avicel(®) PH102 (microcrystalline cellulose) and different amounts of the respective silicate were compacted and analyzed for their tabletability (tensile strength vs. compaction pressure) as well as their Heckel plot. With Neusilin(®) the tabletability appeared to be independent of the silicate concentration, whereas with Florite(®) an increasing silicate concentration led to a higher tensile strength. In contrast, the addition of Silica Aerogel and Aerosil(®) resulted in a decrease of the tensile strength. With Aerosil(®) a maximum tolerable concentration of 20% [w/w] was determined. Plastic deformation of all powder blends decreased with increasing silicate concentration. This effect was most pronounced with Aerosil(®) and least with Florite(®). Tablets with acceptable tensile strength were obtained with all plain silicates except for Aerosil(®). Therefore, these silicates may be used in tablet formulations, e.g. as carrier materials for liquid or amorphous drugs.

Effects of pigeon pea and plantain starches on the compressional, mechanical, and disintegration properties of paracetamol tablets.

PubMed

Dare, Kunle; Akin-Ajani, Dorothy O; Odeku, Oluwatoyin A; Itiola, Oludele A; Odusote, Omotunde M

2006-03-01

A study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T--a measure of bond strength) and brittle fracture index (BFI--a measure of lamination tendency). The ranking for the mean yield pressure, P(y), for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for P(k), an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain starch, on the other hand, would be more useful where faster disintegration of tablet is desired. The results show that the starches could be useful in various formulations depending on the intended use of the tablets with the implication that the experimental starches can be developed for commercial purposes.

Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties.

PubMed

Petrovick, Gustavo Freire; Kleinebudde, Peter; Breitkreutz, Jörg

2018-01-01

Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash ® and Parteck ® ODT) on properties of the tablets (friability, tensile strength, and disintegration time). ODTs (15 mm, flat-faced) with solid lipid pellets (250-1000 µm in diameter) containing 500 mg of metformin HCl, presenting immediate drug release profile and taste-masked properties, were targeted. During compression, a strong lamination of the tablets containing Parteck ® ODT was observed. This phenomenon was prominently observed when high compression forces (≥5 kN) and high excipient amounts (≥40%; w/w) were used. On the other hand, the DoE focused on tablets with Ludiflash ® showed better results regarding the production of ODTs. A positive influence of the compression force on the tensile strength and disintegration time of the tablets, regarding specifications of the Ph. Eur., was observed. The increase in the amount of this excipient resulted in fast disintegrating tablets, however, a negative influence on the tensile strength was noticed. After optimization of the parameters and formulation, based on the DoE results and considering the Ph. Eur. specifications for tablets, ODTs based on lipid pellets containing metformin HCl presenting immediate release profile (85% drug release in less than 30 min) and taste-masked properties (determined by an electronic tongue) were successfully obtained. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlating bilayer tablet delamination tendencies to micro-environmental thermodynamic conditions during pan coating.

PubMed

Zacour, Brian M; Pandey, Preetanshu; Subramanian, Ganeshkumar; Gao, Julia Z; Nikfar, Faranak

2014-06-01

The objective of this study was to determine the impact that the micro-environment, as measured by PyroButton data loggers, experienced by tablets during the pan coating unit operation had on the layer adhesion of bilayer tablets in open storage conditions. A full factorial design of experiments (DOE) with three center points was conducted to study the impact of final tablet hardness, film coating spray rate and film coating exhaust temperature on the delamination tendencies of bilayer tablets. PyroButton data loggers were placed (fixed) at various locations in a pan coater and were also allowed to freely move with the tablet bed to measure the micro-environmental temperature and humidity conditions of the tablet bed. The variance in the measured micro-environment via PyroButton data loggers accounted for 75% of the variance in the delamination tendencies of bilayer tablets on storage (R(2 )= 0.75). A survival analysis suggested that tablet hardness and coating spray rate significantly impacted the delamination tendencies of the bilayer tablets under open storage conditions. The coating exhaust temperature did not show good correlation with the tablets' propensity to crack indicating that it was not representative of the coating micro-environment. Models created using data obtained from the PyroButton data loggers outperformed models created using primary DOE factors in the prediction of bilayer tablet strength, especially upon equipment or scale transfers. The coating micro-environment experienced by tablets during the pan coating unit operation significantly impacts the strength of the bilayer interface of tablets on storage.

A hybrid approach to predict the relationship between tablet tensile strength and compaction pressure using analytical powder compression.

PubMed

Persson, Ann-Sofie; Alderborn, Göran

2018-04-01

The objective was to present a hybrid approach to predict the strength-pressure relationship (SPR) of tablets using common compression parameters and a single measurement of tablet tensile strength. Experimental SPR were derived for six pharmaceutical powders with brittle and ductile properties and compared to predicted SPR based on a three-stage approach. The prediction was based on the Kawakita b -1 parameter and the in-die Heckel yield stress, an estimate of maximal tensile strength, and a parameter proportionality factor α. Three values of α were used to investigate the influence of the parameter on the SPR. The experimental SPR could satisfactorily be described by the three stage model, however for sodium bicarbonate the tensile strength plateau could not be observed experimentally. The shape of the predicted SPR was to a minor extent influenced by the Kawakita b -1 but the width of the linear region was highly influenced by α. An increased α increased the width of the linear region and thus also the maximal predicted tablet tensile strength. Furthermore, the correspondence between experimental and predicted SPR was influenced by the α value and satisfactory predictions were in general obtained for α = 4.1 indicating the predictive potential of the hybrid approach. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Deterred drug abuse using superabsorbent polymers.

PubMed

Mastropietro, David J; Muppalaneni, Srinath; Omidian, Hossein

2016-11-01

This study aimed to determine whether selected superabsorbent polymers (SAPs) could be used as a suitable alternative to thwart extraction, filtration, and syringeability attempts for abuse. Many abuse-deterrent formulations (ADFs) rely on high molecular weight polymers such as poly(ethylene oxide) to provide crush and extraction resistance. However, these polymers suffer from slow dissolution kinetics, and are susceptible to a variety of abuse conditions. Several commercially available SAPs were evaluated for swelling behavior in extraction solvents, and tableting properties. Post-compaction abuse properties were evaluated by recoverable volume and syringeability after solvent extraction. Drug release and percent drug extraction were conducted using tramadol HCl as a model drug. Certain SAPs had the ability to rapidly imbibe solvent and effectively stop extraction processes in a variety of solvents, including water and water/alcohol mixtures. Tablets containing SAP and drug showed no effect on drug release in vitro. SAPs possess adequate properties for tableting, and maintain their high and fast swelling properties after compaction. The fast and extensive interactions of SAPs with aqueous medium are a major advantage over non-crosslinked high molecular weight viscosifying agents such as poly(ethylene oxide).

Multispectral UV imaging for fast and non-destructive quality control of chemical and physical tablet attributes.

PubMed

Klukkert, Marten; Wu, Jian X; Rantanen, Jukka; Carstensen, Jens M; Rades, Thomas; Leopold, Claudia S

2016-07-30

Monitoring of tablet quality attributes in direct vicinity of the production process requires analytical techniques that allow fast, non-destructive, and accurate tablet characterization. The overall objective of this study was to investigate the applicability of multispectral UV imaging as a reliable, rapid technique for estimation of the tablet API content and tablet hardness, as well as determination of tablet intactness and the tablet surface density profile. One of the aims was to establish an image analysis approach based on multivariate image analysis and pattern recognition to evaluate the potential of UV imaging for automatized quality control of tablets with respect to their intactness and surface density profile. Various tablets of different composition and different quality regarding their API content, radial tensile strength, intactness, and surface density profile were prepared using an eccentric as well as a rotary tablet press at compression pressures from 20MPa up to 410MPa. It was found, that UV imaging can provide both, relevant information on chemical and physical tablet attributes. The tablet API content and radial tensile strength could be estimated by UV imaging combined with partial least squares analysis. Furthermore, an image analysis routine was developed and successfully applied to the UV images that provided qualitative information on physical tablet surface properties such as intactness and surface density profiles, as well as quantitative information on variations in the surface density. In conclusion, this study demonstrates that UV imaging combined with image analysis is an effective and non-destructive method to determine chemical and physical quality attributes of tablets and is a promising approach for (near) real-time monitoring of the tablet compaction process and formulation optimization purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

PubMed

Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the world. Tablets are often split to modify dose strength, make swallowing easier, and reduce cost to the consumer. To better address product quality for this widely used practice, the U.S. Food and Drug Administration (FDA) published a Guidance for Industry that addresses tablet splitting. The guidance provides testing criteria for scored tablets, which is a part of the FDA review process for drugs. The model drugs selected for this study were amlodipine and gabapentin, which have different sizes, shapes, and tablet scores. Whole and split amlodipine tablets were tested for drug content because of a concern that the low-dose strength may cause greater variability. Whole and split gabapentin tablets were tested for weight variation because of their higher dosage strength of 600 mg. All whole tablets met the acceptance criteria for the Uniformity of Dosage Units based on the guidance recommendations. When unscored amlodipine tablets were split by a splitter, all formulations did not meet the acceptance criteria. When fully scored gabapentin tablets were split by hand and by splitter, they met the acceptance criteria. The findings of this FDA study indicated physical characteristics such as size, shape, and tablet score can affect the uniformity of split tablets. © PDA, Inc. 2016.

[The dry binders, Vivapur 102, Vivapur 12 and the effect of magnesium stearate on the strength of tablets containing these substances].

PubMed

Muzíková, J; Horácek, J

2003-07-01

Vivapur is microcrystalline cellulose manufactured by the German firm J. Rettenmeier & Söhne GmbH + Co. The types Vivapur 102 and 12 enjoy priority use as dry binders for direct tablet compression. The present paper evaluates tensile strength of tablets made from these substances and the effect of an addition of the lubricant magnesium stearate in connection with its concentration and the conditions of the process of mixing, particularly the period and intensity of mixing. The tested concentrations of stearate were 0.4 and 0.8%, the tested periods of mixing being 2.5, 5, 10, and 20 minutes, intensities of mixing 17 and 34 rot./min. Sensitivity of dry binders to added stearate was evaluated by means of the LSR (lubricant sensitivity ratio) values. The results demonstrated higher sensitivity to an addition of the lubricant in Vivapur 12 than in Vivapur 102. In the first part of the paper focused on the effect of stearate concentration on tensile strength of tablets, Vivapur 102 was also compared with Avicel PH-102. Tablets from Vivapur 102 alone were stronger than those from Avicel PH-102. A concentration of stearate of 0.8% decreased the binding capacity of Vivapur 102 more than that of Avicel PH-102. With a prolonged period of mixing and increased intensity of mixing with stearate, tensile strength of tablets from both Vivapur types was decresed, and a prolonged period of mixing exerted a more marked effect on Vivapur 12 and increased intensity of mixing, on Vivapur 102.

Roll Compaction/Dry Granulation of Dibasic Calcium Phosphate Anhydrous-Does the Morphology of the Raw Material Influence the Tabletability of Dry Granules?

PubMed

Grote, Simon; Kleinebudde, Peter

2018-04-01

The influence of raw material particle morphology on the tabletabilty of dry granules was investigated. Therefore, dibasic calcium phosphate anhydrous was used as a model material. One milled grade, 2 agglomerated grades with different porosities, and a functionalized structure, that is, an agglomerate formed by very small primary particles, were included. Particle size, density, and specific surface area of raw materials were measured. The starting materials and 2 fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force, granule size, and lubrication on tablet tensile strength was evaluated. All materials showed a loss in tabletability induced by a previous compaction step but to a varying extent. Only in case of the functionalized calcium phosphate morphology, this effect depended on the specific compaction force. In contrast to the other materials, the tabletability of functionalized calcium phosphate was influenced by the granule size. This effect was not related to an overlubrication as internal and external lubrication resulted in similar tensile strengths. A clear influence of the particle morphology on tablet strength was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. The functionalized dibasic calcium phosphate and the more porous agglomerate performed as potential filler/binder in the field of roll compaction/dry granulation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

PubMed

Puri, Vibha; Brancazio, Dave; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L

2017-11-01

The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

The Influence of Formulation and Manufacturing Process Parameters on the Characteristics of Lyophilized Orally Disintegrating Tablets

PubMed Central

Jones, Rhys J.; Rajabi-Siahboomi, Ali; Levina, Marina; Perrie, Yvonne; Mohammed, Afzal R.

2011-01-01

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. PMID:24310589

Environmental contamination with methotrexate in Canadian community pharmacies.

PubMed

Merger, Delphine; Tanguay, Cynthia; Langlois, Éric; Lefebvre, Michel; Bussières, Jean-François

2013-01-01

To evaluate environmental contamination with methotrexate, cyclophosphamide, and ifosfamide in Quebec, Canada, community pharmacies and to describe hazardous drug handling practices in these pharmacies. Three standardized sites were sampled in each participating community pharmacy. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by high-performance liquid chromatography tandem mass spectrometry. The limits of detection were 0.10, 0.12, and 0.41 ng/mL for cyclophosphamide, ifosfamide, and methotrexate, respectively. Nine working practices were assessed. 20 community pharmacies participated in the study, and 60 samples were analyzed. No traces of cyclophosphamide or ifosfamide were detected. Traces of methotrexate were found in 12 of 20 pharmacies (60%). Of the 20 pharmacies, 8 (40%) had a storage space reserved for hazardous drugs and none had a preparation area reserved for handling methotrexate tablets. All of the participating community pharmacies had a tablet counter reserved for the handling of hazardous drugs, and all pharmacies cleaned their tablet counter reserved for handling hazardous drugs after use. None of the pharmacies cut or crushed methotrexate tablets. The growing number of hazardous drugs represents a challenge for community pharmacies. Community pharmacists must be made aware of their presence and the need to comply with personal protection measures to reduce staff occupational exposure to hazardous drugs.

Quality-by-design III: application of near-infrared spectroscopy to monitor roller compaction in-process and product quality attributes of immediate release tablets.

PubMed

Kona, Ravikanth; Fahmy, Raafat M; Claycamp, Gregg; Polli, James E; Martinez, Marilyn; Hoag, Stephen W

2015-02-01

The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller compaction process parameters, compression force (CFt), and formulation variables identified from our earlier studies were evaluated in more detail. Multivariate principal component analysis (PCA) and partial least square (PLS) models were developed during the development stage and used as a control tool to predict the quality of granules and tablets. Validated models were used to monitor and control batches manufactured at different sites to assess their robustness to change. The results showed that roll pressure (RP) and CFt played a critical role in the quality of the granules and the finished product within the range tested. Replacing binder source did not statistically influence the quality attributes of the granules and tablets. However, lubricant type has significantly impacted the granule size. Blend uniformity, crushing force, disintegration time during the manufacturing was predicted using validated PLS regression models with acceptable standard error of prediction (SEP) values, whereas the models resulted in higher SEP for batches obtained from different manufacturing site. From this study, we were able to identify critical factors which could impact the quality attributes of the CIP IR tablets. In summary, we demonstrated the ability of near-infrared spectroscopy coupled with chemometrics as a powerful tool to monitor critical quality attributes (CQA) identified during formulation development.

Evaluation of the material and tablet formation properties of modified forms of Dioscorea starches.

PubMed

Odeku, Oluwatoyin A; Picker-Freyer, Katharina M

2009-11-01

Starches obtained from four different Dioscorea species-namely, White yam (Dioscorea rotundata), Bitter yam (Dioscorea dumetorum), Chinese yam (Dioscorea oppositifolia), and Water yam (Dioscorea alata)-were modified by cross-linking, hydroxypropylation, and dual modification-cross-linking followed by hydroxypropylation. The physicochemical, material, and tablet properties of the modified starches were investigated with the aim of understanding their properties to determine their potential use for different applications. The tablet formation properties were assessed using 3D modeling, the Heckel equation, and force-displacement profiles. The analyzed tablet properties were elastic recovery, compactibility, and disintegration. The result indicates that the modifications generally increased the swelling power for all the starches in the rank order hydroxypropyl > hydroxypropylated cross-linked > cross-linked (CL) while the solubility did not show a clear-cut pattern. This indicates that hydroxypropylation generally showed the strongest effects on swelling. Furthermore, hydroxypropylation improved the hot water swelling of the CL starches. The modifications did not cause any detectable morphological change in the starch granules shape or size although slight rupture was observed in some granules. CL starch had the lowest water sorption capacity and hydroxypropylation increased the sorption capacity of the CL starches. The material property results indicate that hydroxypropylation and cross-linking did not significantly improve the flowability and compressibility but improved bonding, which resulted in an increased compaction and higher tablet crushing force even though they all disintegrated rapidly. Thus, the modified Dioscorea starches showed potentials for development as new excipients in solid dosage form design, and they could be useful as disintegrants or for Soft tableting.

Tableting Properties and Compression Models of Labisia pumila Tablets.

PubMed

Etti, C J; Yusof, Y A; Chin, N L; Mohd Tahir, S

2017-03-04

The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.

A STUDY OF COMPRESSION PROCESS AND PROPERTIES OF TABLETS WITH MICROCRYSTALLINE CELLULOSE AND COLLOIDAL SILICON DIOXIDE.

PubMed

Muzikova, Jitka; Louzenska, Marketa; Pekarek, Tomas

2016-09-01

This paper compares the compressibility and properties of tablets from Prosolv SMCC 90 and a mixture of Avicel PH-102 and colloidal silicon dioxide with a different specific surface. The effect of an addition of the lubricant magnesium stearate on these parameters under varying conditions of mixing and the homogeneity of the lubricant in the mixtures are also examined. Compressibility is evaluated by means of the energy balance of the compression process; the examined properties of tablets are tensile strength and disintegration time. The total energy of compression was increased with compression force, the highest being in Prosolv SMCC 90. Its values did not differ for differing conditions of mixing with the lubricant. Plasticity was slightly decreased with compression force and in the mixture with magnesium stearate it was not influenced by the conditions of mixing. Tablets made from Prosolv SMCC 90 and Avicel PH-102 were stronger than those from the mixtures from Avicel PH-102 and both types of Aerosil. The addition of magnesium stearate markedly decreased the strength of tablets from Avicel PH-102. An increase in the period and frequency of mixing with the lubricant resulted in a further decrease in strength. Disintegration time was longer in tablets from Avicel PH-102 and Prosolv SMCC 90, and it was further prolonged by an addition of magnesium stearate.

Utilization of recycled cathode ray tubes glass in cement mortar for X-ray radiation-shielding applications.

PubMed

Ling, Tung-Chai; Poon, Chi-Sun; Lam, Wai-Shung; Chan, Tai-Po; Fung, Karl Ka-Lok

2012-01-15

Recycled glass derived from cathode ray tubes (CRT) glass with a specific gravity of approximately 3.0 g/cm(3) can be potentially suitable to be used as fine aggregate for preparing cement mortars for X-ray radiation-shielding applications. In this work, the effects of using crushed glass derived from crushed CRT funnel glass (both acid washed and unwashed) and crushed ordinary beverage container glass at different replacement levels (0%, 25%, 50%, 75% and 100% by volume) of sand on the mechanical properties (strength and density) and radiation-shielding performance of the cement-sand mortars were studied. The results show that all the prepared mortars had compressive strength values greater than 30 MPa which are suitable for most building applications based on ASTM C 270. The density and shielding performance of the mortar prepared with ordinary crushed (lead-free) glass was similar to the control mortar. However, a significant enhancement of radiation-shielding was achieved when the CRT glasses were used due to the presence of lead in the glass. In addition, the radiation shielding contribution of CRT glasses was more pronounced when the mortar was subject to a higher level of X-ray energy. Copyright © 2011 Elsevier B.V. All rights reserved.

Crushed and Injected Buprenorphine Tablets: Characteristics of Princeps and Generic Solutions

PubMed Central

Bouquié, Régis; Wainstein, Laura; Pilet, Paul; Mussini, Jean-Marie; Deslandes, Guillaume; Clouet, Johann; Dailly, Eric; Jolliet, Pascale; Victorri-Vigneau, Caroline

2014-01-01

Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened. PMID:25474108

A reassessment of the compressive strength properties of southern yellow pine bark

Treesearch

Thomas L. Eberhardt

2007-01-01

Samples of southern yellow pine outer bark and wood were tested in compression to determine values for modulus of elasticity, stress at proportional limit, and maximum crushing strength. Results reported here resolve inconsistencies in the compressive strength data previously reported by others for pine bark. Testing of solvent-treated bark blocks suggests that...

NMR imaging of chitosan and carboxymethyl starch tablets: swelling and hydration of the polyelectrolyte complex.

PubMed

Wang, Y J; Assaad, E; Ispas-Szabo, P; Mateescu, M A; Zhu, X X

2011-10-31

The hydration and swelling properties of the tablets made of chitosan, carboxymethyl starch, and a polyelectrolyte complex of these two polysaccharides have been studied by NMR imaging. We studied the effect of pH and ionic strength on the swelling of the tablets and on the diffusion of fluid into the tablets in water and simulated physiological fluids. The pH value of the fluids exerts a more significant effect than their ionic strengths on the swelling of the tablets. The tablets are compared also with those made of cross-linked high amylose starch. The formation of complex helps to keep the integrity of the tablets in various media and render a slow and restricted swelling similar to that of the tablets of the cross-linked high amylase starch, which is significantly lower than the swelling of chitosan and of carboxymethyl starch. The capacities to modulate the release rate of drugs in different media are discussed by comparing the matrices and evaluating the preparation process of the complex. A sustained release of less soluble drugs such as aspirin in gastrointestinal fluids can be provided by the complex, due to the ionic interaction and hydrogen bonding between the drug and the biopolymer complex. Copyright © 2011 Elsevier B.V. All rights reserved.

A study of the properties of tablets from coprocessed dry binders composed of alpha-lactose monohydrate and different types of cellulose.

PubMed

Muzíková, J; Zvolánková, J

2007-12-01

The paper evaluates the differences between the properties of tablets from two coprocessed dry binders based on alpha-lactose monohydrate and cellulose, MicroceLac 100 and Cellactose 80. The substances differ in the type of contained cellulose; MicroceLac 100 contains 25% of microcrystalline cellulose, Cellactose 80, 25% of powdered cellulose. The properties under study included the tensile strength and disintegration time in dependence on compression force, addition of two concentrations of the lubricant sodium stearylfumarate (Pruv) and a 50% addition of the active ingredients ascorbic acid and acetylsalicylic acid. Using one of the compression forces, the effect of Pruv and magnesium stearate on the above-mentioned properties were compared. In the compression forces of 6 and 8 kN the strength of the compacts from pure Cellactose 80 was lower than that of those from MicroceLac 100 both without and with the lubricant. The lubricant sensitivity of dry binders depended on compression force. Pruv decreased the strength of compacts less than magnesium stearate. The tablets from Cellactose 80 possessed a longer disintegration time than those from MicroceLac 100, excepting the tableting materials containing 0.4 Pruv with a compression force of 6 kN. Disintegration time was prolonged with the use of sodium stearylfumarate and it was increased with compression force much more markedly in the case of Cellactose 80. In the presence of ascorbic acid, the strength of tablets was decreased in the case of both dry binders, but it was higher with MicroceLac100, disintegration time was very short and independent of the type of the dry binder. In the case of acetylsalicylic acid, the strength of tablets was higher with a lesser influence of the type of the dry binder, and disintegration time was longer and especially in the case of Cellactose 80 increased with increasing concentration of Pruv.

Properties of concrete blocks prepared with low grade recycled aggregates.

PubMed

Poon, Chi-Sun; Kou, Shi-cong; Wan, Hui-wen; Etxeberria, Miren

2009-08-01

Low grade recycled aggregates obtained from a construction waste sorting facility were tested to assess the feasibility of using these in the production of concrete blocks. The characteristics of the sorted construction waste are significantly different from that of crushed concrete rubbles that are mostly derived from demolition waste streams. This is due to the presence of higher percentages of non-concrete components (e.g. >10% soil, brick, tiles etc.) in the sorted construction waste. In the study reported in this paper, three series of concrete block mixtures were prepared by using the low grade recycled aggregates to replace (i) natural coarse granite (10mm), and (ii) 0, 25, 50, 75 and 100% replacement levels of crushed stone fine (crushed natural granite <5mm) in the concrete blocks. Test results on properties such as density, compressive strength, transverse strength and drying shrinkage as well as strength reduction after exposure to 800 degrees C are presented below. The results show that the soil content in the recycled fine aggregate was an important factor in affecting the properties of the blocks produced and the mechanical strength deceased with increasing low grade recycled fine aggregate content. But the higher soil content in the recycled aggregates reduced the reduction of compressive strength of the blocks after exposure to high temperature due probably to the formation of a new crystalline phase. The results show that the low grade recycled aggregates obtained from the construction waste sorting facility has potential to be used as aggregates for making non-structural pre-cast concrete blocks.

Static and dynamic crush testing and analysis of a rail vehicle corner structural element

DOT National Transportation Integrated Search

1999-11-01

This paper presents the results of an experimental study to establish the strength and energy absorption capability of cab car rail vehicle corner structures built to current strength requirements and for structures modified to carry higher loads and...

Optimizing the use of natural gravel Brantas river as normal concrete mixed with quality fc = 19.3 Mpa

NASA Astrophysics Data System (ADS)

Limantara, A. D.; Widodo, A.; Winarto, S.; Krisnawati, L. D.; Mudjanarko, S. W.

2018-04-01

The use of natural gravel (rivers) as concrete mixtures is rarely encountered after days of demands for a higher strength of concrete. Moreover, today people have found High-Performance Concrete which, when viewed from the rough aggregate consisted mostly of broken stone, although the fine grain material still used natural sand. Is it possible that a mixture of concrete using natural gravel as a coarse aggregate is capable of producing concrete with compressive strength equivalent to a concrete mixture using crushed stone? To obtain information on this, a series of tests on concrete mixes with crude aggregates of Kalitelu Crusher, Gondang, Tulungagung and natural stone (river gravel) from the Brantas River, Ngujang, Tulungagung in the Materials Testing Laboratory Tugu Dam Construction Project, Kab. Trenggalek. From concrete strength test results using coarse material obtained value 19.47 Mpa, while the compressive strength of concrete with a mixture of crushed stone obtained the value of 21.12 Mpa.

Finasteride. Does it affect spermatogenesis and pregnancy?

PubMed Central

Pole, M.; Koren, G.

2001-01-01

QUESTION: A few women have asked me whether finasteride, taken by their partners for male pattern baldness, will affect their pregnancies. The product monograph is very alarming: it sounds as if even handling the medication could cause harm, especially to a male fetus. Should a man stop taking finasteride if his partner is planning pregnancy or is pregnant? What is the risk to the fetus if its mother accidentally handles crushed or broken tablets? ANSWER: To date, there are no reports of adverse pregnancy outcomes among women exposed to finasteride. Taking 1 mg of finasteride daily did not have any clinically significant effect on men's semen. Absorption through the skin while handling tablets is extremely unlikely to cause fetal exposure or harm. There is no reason to discontinue the drug. Motherisk is currently following up women who are pregnant or planning pregnancy and whose partners are taking finasteride. PMID:11785276

Effects of plantain and corn starches on the mechanical and disintegration properties of paracetamol tablets.

PubMed

Akin-Ajani, Olufunke D; Itiola, Oludele A; Odeku, Oluwatoyin A

2005-10-22

The effects of plantain starch obtained from the unripe fruit of the plant Musa paradisiaca L. (Musaceae) on the mechanical and disintegration properties of paracetamol tablets have been investigated in comparison with the effects of corn starch BP using a 2(3) factorial experimental design. The individual and combined effects of nature of starch binder (N), concentration of starch binder (C), and the relative density of tablet (RD) on the tensile strength (TS), brittle fracture index (BFI), and disintegration time (DT) of the tablets were investigated. The ranking of the individual effects on TS was RD > C > N, on BFI was C > RD > N and on DT was N > C > RD. The ranking for the interaction effects on TS and DT was N-C > N-RD > C-RD, while that on BFI was N-C > C-RD > N-RD. Changing nature of starch from a "low" (plantain starch) to a "high" (corn starch) level, increasing the concentration of starch binding agent from 2.5% to 10.0% wt/wt, and increasing relative density of the tablet from 0.80 to 0.90, led to increase in the values of TS and DT, but a decrease in BFI. Thus, tablets containing plantain starch had lower tensile strength and disintegration time values than those containing corn starch, but showed better ability to reduce the lamination and capping tendency in paracetamol tablet formulation. The interaction between N and C was significantly (P < .001) higher than those between N and RD and between C and RD. There is therefore the need to carefully choose the nature (N) and concentration (C) of starch used as binding agent in tablet formulations to obtain tablets of desired bond strength and disintegration properties. Furthermore, plantain starch could be useful as an alternative binding agent to cornstarch, especially where faster disintegration is required and the problems of lamination and capping are of particular concern.

Effect of roll-compaction and milling conditions on granules and tablet properties.

PubMed

Perez-Gandarillas, Lucia; Perez-Gago, Ana; Mazor, Alon; Kleinebudde, Peter; Lecoq, Olivier; Michrafy, Abderrahim

2016-09-01

Dry granulation is an agglomeration process used to produce size-enlarged particles (granules), improving the handling properties of powders such as flowability. In this process, powders are compacted using a roll press to produce ribbons, which are milled in granules used further in the tableting process. The granule and tablet properties are influenced by the existence of different designs of the roll compactors, milling systems and the interaction between process parameters and raw material properties. The main objective of this work was to investigate how different roll-compaction conditions and milling process parameters impact on ribbons, granules and tablet properties, highlighting the role of the sealing system (cheek plates and rimmed roll). In this context, two common excipients differing in their mechanical behaviour (MCC and mannitol) are used. The study is based on the analysis of granule size distribution together with the characterization of loss of compactability during die compaction. Results show that the tensile strength of tablets is lower when using granules than when the raw materials are compressed. Moreover, the plastic material (MCC) is more sensitive than the brittle one (mannitol). Regarding the roll-force, it is observed that the higher the roll force, the lower the tensile strength of tablets from granulated material is. These findings are in agreement with the literature. The comparison of sealing systems shows that the rimmed-roll system leads to slightly stronger tablets than the use of cheek plates. In addition, the use of the rimmed-roll system reduces the amount of fines, in particular when high roll force is applied. Overall, it can be concluded that roll-compaction effect is predominant over the milling effect on the production of fines but less significant on the tablet properties. This study points out that the balance between a good flowability by reducing the amount of fines and appropriate tablet strength is achieved with rimmed-roll and the highest roll-force used. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

PubMed

Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

2017-08-01

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

Discrete particle modeling and micromechanical characterization of bilayer tablet compaction.

PubMed

Yohannes, B; Gonzalez, M; Abebe, A; Sprockel, O; Nikfar, F; Kiang, S; Cuitiño, A M

2017-08-30

A mechanistic particle scale model is proposed for bilayer tablet compaction. Making bilayer tablets involves the application of first layer compaction pressure on the first layer powder and a second layer compaction pressure on entire powder bed. The bonding formed between the first layer and the second layer particles is crucial for the mechanical strength of the bilayer tablet. The bonding and the contact forces between particles of the first layer and second layer are affected by the deformation and rearrangement of particles due to the compaction pressures. Our model takes into consideration the elastic and plastic deformations of the first layer particles due to the first layer compaction pressure, in addition to the mechanical and physical properties of the particles. Using this model, bilayer tablets with layers of the same material and different materials, which are commonly used pharmaceutical powders, are tested. The simulations show that the strength of the layer interface becomes weaker than the strength of the two layers as the first layer compaction pressure is increased. The reduction of strength at the layer interface is related to reduction of the first layer surface roughness. The reduced roughness decreases the available bonding area and hence reduces the mechanical strength at the interface. In addition, the simulations show that at higher first layer compaction pressure the bonding area is significantly less than the total contact area at the layer interface. At the interface itself, there is a non-monotonic relationship between the bonding area and first layer force. The bonding area at the interface first increases and then decreases as the first layer pressure is increased. These results are in agreement with findings of previous experimental studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure.

PubMed

Badal Tejedor, Maria; Nordgren, Niklas; Schuleit, Michael; Rutland, Mark W; Millqvist-Fureby, Anna

2015-01-01

Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture. Copyright © 2015 Elsevier B.V. All rights reserved.

Roll Compaction and Tableting of High Loaded Metformin Formulations Using Efficient Binders.

PubMed

Arndt, Oscar-Rupert; Kleinebudde, Peter

2018-04-23

Metformin has a poor tabletability and flowability. Therefore, metformin is typically wet granulated with a binder before tableting. To save production costs, it would be desirable to implement a roll compaction/dry granulation (RCDG) process for metformin instead of using wet granulation. In order to implement RCDG, the efficiency of dry binders is crucial to ensure a high drug load and suitable properties of dry granules and tablets. This study evaluates dry granules manufactured by RCDG and subsequently tableting of high metformin content formulations (≥ 87.5%). Based on previous results, fine particle grades of hydroxypropylcellulose and copovidone in different fractions were compared as dry binders. The formulations are suitable for RCDG and tableting. Furthermore, results can be connected to in-die and out-of-die compressibility analysis. The addition of 7% of dry binder is a good compromise to generate sufficient mechanical properties on the one hand, but also to save resources and ensure a high metformin content on the other hand. Hydroxypropylcellulose was more efficient in terms of granule size, tensile strength and friability. Three percent croscarmellose was added to reach the specifications of the US Pharmacopeia regarding dissolution. The final formulation has a metformin content of 87.5%. A loss in tabletability does not occur for granules compressed at different specific compaction forces, which displays a robust tensile strength of tablets independent of the granulation process.

Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

PubMed

Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

2011-10-09

Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets.

PubMed

ElShaer, Amr; Kaialy, Waseem; Akhtar, Noreen; Iyire, Affiong; Hussain, Tariq; Alany, Raid; Mohammed, Afzal R

2015-10-01

The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y=28.01MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (σ) increased from 0.2±0.05N/mm(2) to 2.85±0.36N/mm(2) upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets' disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (σ) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of tableting and tablet properties of Kollidon SR: the influence of moisture and mixtures with theophylline monohydrate.

PubMed

Hauschild, Karsten; Picker-Freyer, Katharina M

2006-02-01

The aim of the study was firstly to investigate the influence of moisture on the tableting and tablet properties of Kollidon SR and secondly to investigate the influence of theophylline monohydrate on the tableting behavior and tablet properties produced from binary mixtures with Kollidon SR. In comparison to Kollidon SR, microcrystalline cellulose (MCC) was used. The glass transition temperature (Tg) of the powder over the whole range of RH (0-90%), and in addition, the Tg of tablets of Kollidon SR were measured. Densities and flowability of the powders were analyzed. The tablets were produced at five different maximum relative densities (rho(rel), max) on an instrumented eccentric tableting machine. They were produced at three different relative humidities (RH), 30%, 45%, and 60% RH for the pure substances and binary mixtures with different ratios of drug and excipient were tableted at 45% RH. The tableting properties were analyzed by 3D modeling, force-displacement profiles, and compactibility plots. First, the Tg of the powder decreased with increasing RH and the Tg of the tablet was 4-8 K lower than the powder. The predominant deformation of Kollidon SR is plastic deformation and Kollidon SR showed a higher compactibility than MCC. The parameters of the 3D model showed an extreme change between 45 and 60% RH, and at higher RH more and more particles deformed elastically. This was confirmed by analysis of force-displacement profiles. At 60% RH, the radial tensile strength of the Kollidon SR tablets was half of the radial tensile strength at 45% RH. The reason is a higher relative energy of plastic deformation than for MCC. This results in a better utilization of the energy to deform the powder into a tablet and the exceeding of the glass transition temperature at higher RH. In conclusion, at 60% RH at the same rho(rel, max), tableting and tablet properties of Kollidon SR are extremely changed since plasticity is significantly higher. In the second part of the study, the insufficient flowability of theophylline monohydrate can be compensated by using Kollidon SR in a mixture with up to 20% theophylline. Further, pressure plasticity e of MCC and Kollidon SR was lowered in the mixture with theophylline monohydrate. The same is valid for the compactibility. The influence of theophylline monohydrate on the pressure plasticity e of the mixtures was better compensated in the mixture with MCC than in a mixture with Kollidon SR. This compensation was also visible by analyzing the force-displacement-profiles. However, hardly any influence on the radial tensile strength could be detected. Kollidon SR and Kollidon SR mixtures exhibited a higher compactibility than MCC and MCC mixtures. The differences became smaller with increasing theophylline content.

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

PubMed

Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

2017-01-01

In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage.

PubMed

Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

2012-01-01

The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage.

[Selected adjuvants as carriers of a dry extract of common ivy (Hedera helix L.)].

PubMed

Marczyński, Zbigniew; Zgoda, Marian Mikołaj; Bodek, Kazimiera Henryka

2011-01-01

The usefulness was tested of selected adjuvants: Vivapur 112, Carmellose calcium, Calcium carbonate CA 740, Calcium carbonate CA 800, Hypromellose as carriers of a dry extract of common ivy (Hedera helix L.) leaves in the process of direct tableting. The quality of the produced tablets was determined by examining their appearance, diameter, thickness, mass resistance to abrasion, crushing and disintegration time. Furthermore, the rate of release of biologically active components from the produced drug form to acceptor fluid was tested in accordance with the requirements of Polish Pharmacopoeia VII (PPVII). An attempt was made to estimate the effect of the used adjuvants on the course of this process. The applied adjuvants and acceptor fluid osmolarity decide significantly about the pharmaceutical availability of the therapeutic agents contained in the extract. The obtained model tablets are characterized by controlled release of biologically active substances, in majority of batches they fulfil the requirements as regards physicochemical properties. The formulation composition of the first batch (Extr. Hederae helices e fol.spir. sicc., Vivapur 112, Carmellose calcium, Sodium Stearyl Fumarate) appeared to be the most effective. The worked out method is optimal and provides technological reproducibility and high durability of the drug form.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, R.C.; Garard, R.J.; Lokhandwala, K.K.

The crush behavior (specific energy absorption and crush load stability) of unidirectional fiber composite rods having tougher matrices than vinyl ester were investigated and compared with the crush behavior of similar specimens having a vinyl ester matrix. The matrices were a cyclic polyester and two rubber-toughened vinyl esters. The specific energy absorption with the cyclic polyester matrix, 180 MJ/m{sup 3}, was slightly lower than that with the vinyl ester matrix, 230 MJ/m{sup 3}. On the other hand, the crush stability was markedly better. The average deviation of the crush load about the mean was as small as 3.5% with themore » cyclic polyester matrix, in contrast to about 12% with the vinyl ester matrix. The higher ductility of the cyclic polyester and the good fiber-matrix bond strength together resulted in less fracturing of the matrix and more uniform kink-band formation across the composite cross section than occurred with the vinyl ester matrix. There was also a reduction in the tendency for fibers at the periphery of the rod to splay outward rather than being crushed. Of the two rubber-toughened vinyl ester matrices, a 30% reduction was found in the average deviation of the crush load about the mean with the matrix toughened with a core-shell material, although no improvement was found with the CTBN rubber-modified vinyl ester resin.« less

Theoretical investigations into the influence of the position of a breaking line on the tensile failure of flat, round, bevel-edged tablets using finite element methodology (FEM) and its practical relevance for industrial tablet strength testing.

PubMed

Podczeck, Fridrun; Newton, J Michael; Fromme, Paul

2014-12-30

Flat, round tablets may have a breaking ("score") line. Pharmacopoeial tablet breaking load tests are diametral in their design, and industrially used breaking load testers often have automatic tablet feeding systems, which position the tablets between the loading platens of the machine with the breaking lines in random orientation to the applied load. The aim of this work was to ascertain the influence of the position of the breaking line in a diametral compression test using finite element methodology (FEM) and to compare the theoretical results with practical findings using commercially produced bevel-edged, scored tablets. Breaking line test positions at an angle of 0°, 22.5°, 45°, 67.5° and 90° relative to the loading plane were studied. FEM results obtained for fully elastic and elasto-plastic tablets were fairly similar, but they highlighted large differences in stress distributions depending on the position of the breaking line. The stress values at failure were predicted to be similar for tablets tested at an angle of 45° or above, whereas at lower test angles the predicted breaking loads were up to three times larger. The stress distributions suggested that not all breaking line angles would result in clean tensile failure. Practical results, however, did not confirm the differences in the predicted breaking loads, but they confirmed differences in the way tablets broke. The results suggest that it is not advisable to convert breaking loads obtained on scored tablets into tablet tensile strength values, and comparisons between different tablets or batches should carefully consider the orientation of the breaking line with respect to the loading plane, as the failure mechanisms appear to vary. Copyright © 2014 Elsevier B.V. All rights reserved.

Observational study on the palatability and tolerability of oral prednisolone and oral dexamethasone in children in Saudi Arabia and the UK.

PubMed

Aljebab, Fahad; Alanazi, Mofadhi; Choonara, Imti; Conroy, Sharon

2018-01-01

Short-course oral corticosteroids are routinely used to treat acute asthma and croup. We evaluated their tolerability and palatability in Saudi Arabian (SA) and UK children. Prospective observational/interview study (3 months in each country). Palatability was evaluated using a 5-point facial Hedonicscale and tolerability by direct questioning of patient/parents. In SA, of 122 patients (2-10 years) recruited, 52 received prednisolone base tablets, 37 prednisolone sodium phosphate syrup and 33 received dexamethasone elixir. In the UK, of 133 patients (2-16 years), 38 received prednisolone base tablets (mainly crushed and dispersed), 42 prednisolone sodium phosphate soluble tablets and 53 received dexamethasone sodium phosphate oral solution.In both countries, dexamethasone had the highest palatability scores (SA mean: 1.97; UK mean: 3) and prednisolone base tablets had the lowest (SA mean: 1.12; UK mean: 1.39). Palatability scores improved for all formulations of prednisolone with each subsequent daily dose.In SA, prednisolone base tablets were associated with more nausea (24vs7 patients) and vomiting (5vs0 patients) than sodium phosphate syrup (p=0.008 and p=0.073, respectively). In the UK, vomiting occurred more frequently with prednisolone base (8 patients) than sodium phosphate soluble tablets (2 patients) (p=0.041).In both centres, dexamethasone was associated with less side effects. Vomiting (1vs0 patients), nausea (7vs3 patients) and abdominal pain (10vs8 patients) occurred more with dexamethasone sodium phosphate solution than dexamethasone elixir. Dexamethasone sodium phosphate solution was the most palatable preparation. Prednisolone base tablets were rated least palatable and were least well tolerated. Palatability scores improved with each dose taken. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Preparation of amine-impregnated silica foams using agar as the gelling agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jardim, Iara M., E-mail: iaramj01@yahoo.com.br

In this work we successfully prepared amine-impregnated gel-cast silica foams using agar and atmospheric air as the gelling agent and heat treatment atmosphere, respectively. The concentration of 3,6-anhydrogalactose in agar was evaluated by ultraviolet–visible spectroscopy (UV–Vis). The obtained foams were examined by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) coupled to mass spectrometry (TG-MS), scanning electron microscopy (SEM), X-ray microtomography (micro-CT), and Archimedes method. The cold crushing strength of the materials prepared in this work was assessed using a mechanical testing stage available in the micro-CT system. The obtained foams exhibited a highly interconnected pore network, with an expressivemore » presence of open pores. Samples heat-treated at 1300 °C for 2 h showed both an expressive porosity (≈ 77%) and a significant cold crushing strength (≈ 1.4 MPa). It was observed that the calcination of the prepared materials at 1200 °C for times as long as 16 h may lead to the rupture of pore walls. FTIR and TG-MS revealed that amine groups were properly incorporated into the foams structure. - Highlights: •Successful preparation of amine-impregnated gel-cast silica foams •Agar used as the gelling agent •Samples with expressive porosity and cold crushing strength •Sintering times as long as 16 h led to the rupture of the pore network.« less

Pilot Scale Production of Activated Carbon Spheres Using Fluidized Bed Reactor and Its Evaluation for the Removal of Hexavalent Chromium from Aqueous Solutions

NASA Astrophysics Data System (ADS)

Tripathi, Nagesh Kumar; Sathe, Manisha

2017-12-01

Large scale production of activated carbon is need of ongoing research due to its excellent adsorption capacity for removal of heavy metals from contaminated solutions. In the present study, polymeric precursor polystyrene beads [Brunauer Emmett Teller (BET) surface area, 46 m2/g; carbon content, 40.64%; crushing strength, 0.32 kg/sphere] were used to produce a new variant of activated carbon, Activated Carbon Spheres (ACS) in a pilot scale fluidized bed reactor. ACS were prepared by carbonization of polymeric precursor at 850 °C followed by activation of resultant material with steam. Prepared ACS were characterized using scanning electron microscope, CHNS analyzer, thermogravimetric analyzer, surface area analyzer and crushing strength tester. The produced ACS have 1009 m2/g BET surface area, 0.89 cm3/g total pore volume, 92.32% carbon content and 1.1 kg/sphere crushing strength with less than 1% of moisture and ash content. The ACS were also evaluated for its potential to remove hexavalent chromium [Cr(VI)] from contaminated solutions. The chromium removal is observed to be 99.1% at initial concentration 50 mg/l, pH 2, ACS dose 1 g/l, contact time 2 h, agitation 120 rpm and temperature 30 °C. Thus ACS can be used as an adsorbent material for the removal of Cr(VI) from contaminated solutions.

Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals.

PubMed

Perumalla, Sathyanarayana R; Paul, Shubhajit; Sun, Changquan C

2016-06-01

5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Relationship between mechanical properties and crystal structure in cocrystals and salt of paracetamol.

PubMed

Ahmed, Hamzah; Shimpi, Manishkumar R; Velaga, Sitaram P

2017-01-01

Objectives were to study mechanical properties of various solid forms of paracetamol and relate to their crystal structures. Paracetamol form I (PRA), its cocrystals with oxalic acid (PRA-OXA) and 4,4-bipyridine (PRA-BPY) and hydrochloride salt (PRA-HCL) were selected. Cocrystals and salt were scaled-up using rational crystallization methods. The resulting materials were subjected to different solid-state characterizations. The powders were sieved and 90-360 µm sieve fraction was considered. These powders were examined by scanning electron microscopy (SEM) and densities were determined. Tablets were made at applied pressures of 35-180 MPa under controlled conditions and the tablet height, diameter and hardness were measured. Tensile strength and porosity of the tablets were estimated using well known models. Crystal structures of these systems were visualized and slip planes were identified. Cocrystal and salt of PRA were physically pure. Sieved powders had comparable morphologies and particle size. The apparent and theoretical densities of powders were similar, but no clear trends were observed. The tensile strengths of these compacts were increased with increasing pressure whereas tabletability decreased in the order oxalic acid > PRA-HCL ≈ PRA-OXA > BPY > PRA-BPY. Tablet tensile strength decreases exponentially with increasing porosity with the exception of PRY-BPY and BPY. Slip plane prediction based on attachment energies may not be independently considered. However, it was possible to explain the improved mechanical properties of powders based on the crystal structure. Cocrystallization and salt formation have introduced structural features that are responsible for improved tableting properties of PRA.

The Development of a Conical Composite Energy Absorber for Use in the Attenuation of Crash/Impact Loads

NASA Technical Reports Server (NTRS)

Littell, Justin D.

2014-01-01

A design for a novel light-weight conical shaped energy absorbing (EA) composite subfloor structure is proposed. This composite EA is fabricated using repeated alternating patterns of a conical geometry to form long beam structures which can be implemented as aircraft subfloor keel beams or frame sections. The geometrical features of this conical design, along with the hybrid composite materials used in the manufacturing process give a strength tailored to achieve a constant 25-40 g sustained crush load, small peak crush loads and long stroke limits. This report will discuss the geometrical design and fabrication methods, along with results from static and dynamic crush testing of 12-in. long subcomponents.

[A study of the properties of tablets from mixtures of two size degrees of alpha-lactose monohydrate and microcrystalline cellulose].

PubMed

Muzíková, J

2006-03-01

The paper examines the strength and disintegration time of compacts from the mixtures of two types of Tablettosas. Tablettosa 70 and Tablettosa 100 with microcrystalline cellulose represented by Vivapur 102. The mixtures of dry binders were prepared in the ratios of 3:1, 1:1, and 1:3. The effect of two concentrations of the lubricant magnesium stearate on the strength and disintegration time of compacts was also examined. Tablet strength increased with higher representation of microcrystalline cellulose in the mixture, and decreased with higher stearate concentration. The compacts from the mixtures with Tablettosa 100 showed higher strength. Disintegration time was highest in the compacts with the largest perccintage of microcrystalline cellulose, and longer in the case of the mixtures with Tablettosa 100. Stearate did not exert a negative effect on disintegration time. In the mixtures of Tablettosas with Vivapur 102 in a ratio of 1:1, the effect of the model active ingredient acetylsalicylic acid on the above-mentioned properties of tablets was tested. acetylsalicylic acid produced a further decrease in the strength of compacts and shortened the disintegration time in more instances in the cased of the mixtures with Tahlettosa 100.

Investigation of the strength of shielded and unshielded underwater electrical cables

NASA Astrophysics Data System (ADS)

Glowe, D. E.; Arnett, S. L.

1981-09-01

The mechanical properties of shielded and unshielded submarine cables (MIL-C-915/8E) were investigated to determine the effect of shielding on cable life, performance, and reliability. Ten cables (five shielded and five unshielded) were selected for laboratory evaluation. A mission profile was developed to establish the mechanical stress limits that cables must endure in service and a test sequence designed to measure tensile strength, flexural abrasion endurance, crush resistance, creep under static tension, and performance in a hull-stuffing tube. The results of this program showed that: (1) DSS-2 cable does not have adequate tensile strength and should have a strength member added. DSS-3 and larger cables have adequate tensile strength with or without the shield; (2) Unshielded DSS-3 type cable does not perform satisfactorily in hull-stuffing tubes; (3) Shielding is not required to meet mission profile specifications for cable crush or flexural abrasion resistance; (4) Construction parameters other than shielding can significantly affect mechanical performance of cable; (5) Unshielded cable construction can result in increased reliability since it permits a thicker single-jacket construction; and (6) Unshielded cable construction can reduce the cost of cable by 8 to 20 percent.

Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

PubMed

Sun, Changquan Calvin

2017-05-01

To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

New insights on poly(vinyl acetate)-based coated floating tablets: characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength.

PubMed

Strübing, Sandra; Abboud, Tâmara; Contri, Renata Vidor; Metz, Hendrik; Mäder, Karsten

2008-06-01

The purpose of this study was to investigate the mechanism of floating and drug release behaviour of poly(vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon SR as an excipient for direct compression and different Kollicoat SR 30 D/Kollicoat IR coats varying from 10 to 20mg polymer/cm2 were investigated regarding drug release in 0.1N HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10mg polymer/cm2 SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics. Poly(vinyl acetate) proved to be an appropriate excipient to ensure safe and reliable drug release. Floating strength measurements offered the possibility to quantify the floating ability of the developed systems and thus to compare different formulations more efficiently. Benchtop MRI studies allowed a deeper insight into drug release and floating mechanisms noninvasively and continuously.

Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

PubMed

Gurpreetarora; Malik, Karan; Rana, Vikas; Singh, Inderbir

2012-01-01

The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.

The use of a combination of different MR methods to study swelling of hydrophilic xanthan matrix tablets at different pHs.

PubMed

Mikac, U; Sepe, A; Kristl, J; Baumgartner, I

2012-01-01

Modified-release matrix tablets have been extensively used by the pharmaceutical industry as one of the most successful oral drug-delivery systems. The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. Magnetic resonance imaging (MRI) is a powerful, non-invasive technique that can help improve our understanding of the gel layer formed on swellable, polymer-matrix tablets, as well as the layer's properties and its influence on the drug release. The aim was to investigate the effects of pH and ionic strength on swelling and to study the influence of structural changes in xanthan gel on drug release. For this purpose a combination of different MRI methods for accurate determination of penetration, swelling and erosion fronts was used. The position of the penetration and swelling fronts were the same, independently of the different xanthan gel structures formed under different conditions of pH and ionic strength. The position of the erosion front, on the other hand, is strongly dependent on pH and ionic strength, as reflected in different thicknesses of the gel layers.

Crystal coating via spray drying to improve powder tabletability.

PubMed

Vanhoorne, V; Peeters, E; Van Snick, B; Remon, J P; Vervaet, C

2014-11-01

A continuous crystal coating method was developed to improve both flowability and tabletability of powders. The method includes the introduction of solid, dry particles into an atomized spray during spray drying in order to coat and agglomerate individual particles. Paracetamol was used as a model drug as it exhibits poor flowability and high capping tendency upon compaction. The particle size enlargement and flowability were evaluated by the mean median particle size and flow index of the resulting powders. The crystal coating coprocessing method was successful for the production of powders containing 75% paracetamol with excellent tableting properties. However, the extent of agglomeration achieved during coprocessing was limited. Tablets compressed on a rotary tablet press in manual mode showed excellent compression properties without capping tendency. A formulation with 75% paracetamol, 5% PVP and 20% amorphous lactose yielded a tensile strength of 1.9 MPa at a compression pressure of 288 MPa. The friability of tablets compressed at 188 MPa was only 0.6%. The excellent tabletability of this formulation was attributed to the coating of paracetamol crystals with amorphous lactose and PVP through coprocessing and the presence of brittle and plastic components in the formulation. The coprocessing method was also successfully applied for the production of directly compressible lactose showing improved tensile strength and friability in comparison to a spray dried direct compression lactose grade.

Direct compression of chitosan: process and formulation factors to improve powder flow and tablet performance.

PubMed

Buys, Gerhard M; du Plessis, Lissinda H; Marais, Andries F; Kotze, Awie F; Hamman, Josias H

2013-06-01

Chitosan is a polymer derived from chitin that is widely available at relatively low cost, but due to compression challenges it has limited application for the production of direct compression tablets. The aim of this study was to use certain process and formulation variables to improve manufacturing of tablets containing chitosan as bulking agent. Chitosan particle size and flow properties were determined, which included bulk density, tapped density, compressibility and moisture uptake. The effect of process variables (i.e. compression force, punch depth, percentage compaction in a novel double fill compression process) and formulation variables (i.e. type of glidant, citric acid, pectin, coating with Eudragit S®) on chitosan tablet performance (i.e. mass variation, tensile strength, dissolution) was investigated. Moisture content of the chitosan powder, particle size and the inclusion of glidants had a pronounced effect on its flow ability. Varying the percentage compaction during the first cycle of a double fill compression process produced chitosan tablets with more acceptable tensile strength and dissolution rate properties. The inclusion of citric acid and pectin into the formulation significantly decreased the dissolution rate of isoniazid from the tablets due to gel formation. Direct compression of chitosan powder into tablets can be significantly improved by the investigated process and formulation variables as well as applying a double fill compression process.

Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage

PubMed Central

Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

2012-01-01

Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

PubMed Central

Arora, Gurpreet; Malik, Karan; Singh, Inderbir; Arora, Sandeep; Rana, Vikas

2011-01-01

The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w). The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer) and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4). Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4) with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations. PMID:22171313

Interfacial elastic relaxation during the ejection of bi-layered tablets.

PubMed

Anuar, M S; Briscoe, B J

2010-03-15

The predilection of a bi-layered tablet to fail in the interface region after its initial formation in the compaction process reduces its practicality as a choice for controlled release solid drug delivery system. Hence, a fundamental appreciation of the governing mechanism that causes the weakening of the interfacial bonds within the bi-layered tablet is crucial in order to improve the overall bi-layered tablet mechanical integrity. This work has shown that the occurrence of the elastic relaxation in the interface region during the ejection stage of the compaction process decreases with the increase in the bi-layered tablet interface strength. This is believed to be due to the increase in the plastic bonding in the interface region. The tablet diametrical elastic relaxation affects the tablet height elastic relaxation, where the impediment of the tablet height expansion is observed when the interface region experiences a diametrical expansion. 2009 Elsevier B.V. All rights reserved.

Insensitivity of compaction properties of brittle granules to size enlargement by roller compaction.

PubMed

Wu, Sy-Juen; Sun, Changquan 'Calvin'

2007-05-01

Pharmaceutical granules prepared by roller compaction often exhibit significant loss of tabletability, that is, reduction in tensile strength, when compared to virgin powder. This may be attributed to granule size enlargement for highly plastic materials, for example, microcrystalline cellulose. The sensitivity of powder compaction properties on granule size variations impacts the robustness of the dry granulation process. We hypothesize that such sensitivity of compaction properties on granule size is minimum for brittle materials because extensive fracture of brittle granules during compaction minimizes differences in initial granule size. We tested the hypothesis using three common brittle excipients. Results show that the fine (44-106 microm), medium (106-250 microm), and coarse (250-500 microm) granules exhibit essentially identical tabletability below a certain critical compaction pressure, 100, 140, and 100 MPa for spray-dried lactose monohydrate, anhydrous dibasic calcium phosphate, and mannitol, respectively. Above respective critical pressure, tabletability lines diverge with smaller granules exhibiting slightly higher tablet tensile strength at identical compaction conditions. Overall, tabletability of brittle granules is insensitive to granule size enlargement. The results provide a scientific basis to the common practice of incorporating brittle filler to a typical tablet formulation processed by roller compaction granulation. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Evaluation of crushed concrete base strength.

DOT National Transportation Integrated Search

2012-12-01

This research project was conducted with two primary objectives, which include: 1) determine whether current Mississippi Department of Transportation (MDOT) requirements for recycled concrete aggregates (RCA) provide adequate materials for a roadway ...

New multifunctional pharmaceutical excipient in tablet formulation based on citric acid-cyclodextrin polymer.

PubMed

Garcia-Fernandez, Maria José; Tabary, Nicolas; Chai, Feng; Cazaux, Frédéric; Blanchemain, Nicolas; Flament, Marie-Pierre; Martel, Bernard

2016-09-25

A β-cyclodextrin (β-CD) polymer obtained by crosslinking β-CD with citric acid in its water-insoluble (PCD-I) and soluble (PCD-S) forms was used as a multifunctional direct compression excipient for tablet designing. PCD-I powder was obtained after grinding the solid fraction through a 200μm grid. PCD-S powder was recovered after lyophilization or spray drying of the PCD-S aqueous solutions, eventually followed by a wet granulation step. Both PCD-I and PCD-S powders were characterized, separately and mixed in variable ratios, based on dynamic water vapor sorption, SEM, particle size distribution, tapped density, compressibility, and flowability. PCD-I and spray dried and lyophilized/wet granulated PCD-S, as well as the mixture PCD-I/PCD-S=90/10, presented optimal free flowing characteristics. Then, PCD-I or PCD-S powders - separately or mixed in variable ratios - were used for tablets preparation by direct compression without adding any other excipient (e.g. binder, lubricant, disintegrant etc). As PCD-I decreased, tablets resistance to crushing and disintegration time increased from 15s to 15min (against 30min for β-CD), showing the improved disintegrant functionality of PCD-I, that rapidly swelled once in contact with water. Finally, PCD was force-fed to Sprague-Dawley rats (2g/kg) which were then observed during 14days for any clinical signs of toxicity. Copyright © 2016. Published by Elsevier B.V.

Prescribing injectable and oral methadone to opiate addicts: results from the 1995 national postal survey of community pharmacies in England and Wales.

PubMed Central

Strang, J.; Sheridan, J.; Barber, N.

1996-01-01

OBJECTIVE--To establish the extent of prescribing injectable and oral methadone to opiate addicts and the practice characteristics and dispensing arrangements attached to these prescriptions. DESIGN--National survey of 25% random sample of community (high street) pharmacies through postal questionnaire, with four mailings. SETTING--England and Wales. SUBJECTS--1 in 4 sample of all 10,616 community pharmacies, stratified by family health services authority. MAIN OUTCOME MEASURES--Data were collected on each prescription for controlled drugs currently being dispensed by pharmacies to misusers, describing the drug, form, dose, source (general practice or hospital; and NHS or private), and numbers of dispensing pick ups a week. RESULTS--Methadone was the opiate most commonly dispensed to misusers (96.0% of 3846 opiate prescriptions). 79.6% of methadone prescriptions were for the oral liquid form, 11.0% for tablet, and 9.3% for injectable ampoules. More than one third of all methadone prescriptions were for weekly or fortnightly pick up, with a further third being for daily pick up. Tablets and ampoules were even less likely to be dispensed on a daily basis. Private prescriptions were significantly more likely than NHS ones to be for tablets or ampoules, to be for substantially higher daily doses, and to be collected on a weekly or fortnightly basis. CONCLUSIONS--The distinctively British practice of prescribing injectable methadone was found to be widespread and, contrary to guidance, to be as prevalent in non-specialist as specialist settings. In view of the frequent crushing and injecting of methadone tablets, clearer more authoritative guidance is needed on the contexts in which injectable methadone (tablets as well as ampoules) should be prescribed and on the responsibilities for monitoring and supervision which should be attached. PMID:8704540

Swallowing Tablets and Capsules Increases the Risk of Penetration and Aspiration in Patients with Stroke-Induced Dysphagia.

PubMed

Schiele, Julia T; Penner, Heike; Schneider, Hendrik; Quinzler, Renate; Reich, Gabriele; Wezler, Nikolai; Micol, William; Oster, Peter; Haefeli, Walter E

2015-10-01

We evaluated the prevalence of difficulties swallowing solid dosage forms in patients with stroke-induced dysphagia and whether swallowing tablets/capsules increases their risk of penetration and aspiration. Concurrently, we explored whether routinely performed assessment tests help identify patients at risk. Using video endoscopy, we evaluated how 52 patients swallowed four different placebos (round, oval, and oblong tablets and a capsule) with texture-modified water (TMW, pudding consistency) and milk and rated their swallowing performance according to the Penetration Aspiration Scale (PAS). Additionally, Daniels Test, Bogenhausener Dysphagiescore, Scandinavian Stroke Scale, Barthel Index, and Tinetti's Mobility Test were conducted. A substantial proportion of the patients experienced severe difficulties swallowing solid oral dosage forms (TMW: 40.4 %, milk: 43.5 %). Compared to the administration of TMW/milk alone, the placebos increased the PAS values in the majority of the patients (TMW: median PAS from 1.5 to 2.0; milk: median PAS from 1.5 to 2.5, each p value <0.0001) and residue values were significantly higher (p < 0.05). Whereas video-endoscopic examination reliably identified patients with difficulties swallowing medication, neither patients' self-evaluation nor one of the routinely performed bedside tests did. Therefore, before video-endoscopic evaluation, many drugs were modified unnecessarily and 20.8 % of these were crushed inadequately, although switching to another dosage form or drug would have been possible. Hence, safety and effectiveness of swallowing tablets and capsules should be evaluated routinely in video-endoscopic examinations, tablets/capsules should rather be provided with TMW than with milk, and the appropriateness of "non per os except medication" orders for dysphagic stroke patients should be questioned.

Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets.

PubMed

Taipale-Kovalainen, Krista; Karttunen, Anssi-Pekka; Ketolainen, Jarkko; Korhonen, Ossi

2018-03-30

The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental design was used to generate a structured study plan which involved 19 runs. The formulation variables studied were the type of lubricant (magnesium stearate or stearic acid) and its concentration (0.5, 1.0 and 1.5%). Process variables were total production feed rate (5, 10.5 and 16kg/h), mixer speed rpm (500, 850 and 1200rpm), and mixer inlet port for lubricant (A or B). The continuous direct compression tableting line consisted of loss-in-weight feeders, a continuous mixer and a tablet press. The Quality Target Product Profile (QTPP) was defined for the final product, as the flowability of powder blends (2.5s), tablet strength (147N), dissolution in 2.5min (90%) and ejection force (425N). A design space was identified which fulfilled all the requirements of QTPP. The type and concentration of lubricant exerted the greatest influence on the design space. For example, stearic acid increased the tablet strength. Interestingly, the studied process parameters had only a very minor effect on the quality of the final product and the design space. It is concluded that the continuous direct compression tableting process itself is insensitive and can cope with changes in lubrication, whereas formulation parameters exert a major influence on the end product quality. Copyright © 2017 Elsevier B.V. All rights reserved.

A Finite Element Analysis for Predicting the Residual Compressive Strength of Impact-Damaged Sandwich Panels

NASA Technical Reports Server (NTRS)

Ratcliffe, James G.; Jackson, Wade C.

2008-01-01

A simple analysis method has been developed for predicting the residual compressive strength of impact-damaged sandwich panels. The method is tailored for honeycomb core-based sandwich specimens that exhibit an indentation growth failure mode under axial compressive loading, which is driven largely by the crushing behavior of the core material. The analysis method is in the form of a finite element model, where the impact-damaged facesheet is represented using shell elements and the core material is represented using spring elements, aligned in the thickness direction of the core. The nonlinear crush response of the core material used in the analysis is based on data from flatwise compression tests. A comparison with a previous analysis method and some experimental data shows good agreement with results from this new approach.

A Finite Element Analysis for Predicting the Residual Compression Strength of Impact-Damaged Sandwich Panels

NASA Technical Reports Server (NTRS)

Ratcliffe, James G.; Jackson, Wade C.

2008-01-01

A simple analysis method has been developed for predicting the residual compression strength of impact-damaged sandwich panels. The method is tailored for honeycomb core-based sandwich specimens that exhibit an indentation growth failure mode under axial compression loading, which is driven largely by the crushing behavior of the core material. The analysis method is in the form of a finite element model, where the impact-damaged facesheet is represented using shell elements and the core material is represented using spring elements, aligned in the thickness direction of the core. The nonlinear crush response of the core material used in the analysis is based on data from flatwise compression tests. A comparison with a previous analysis method and some experimental data shows good agreement with results from this new approach.

Selective batch crushing in the coal-preparation shop at OAO NTMK

DOE Office of Scientific and Technical Information (OSTI.GOV)

N.A. Berkutov; Yu.V. Stepanov; P.V. Shtark

In September 2004, after reconstruction at OAO Nizhnetagil'skii Metallurgicheskii Kombinat (NTMK), blast furnace 6 went into operation for the production of vanadium from hot metal. At the startup of furnace 6, besides optimising its composition; it was decided to restore selective crushing of the coal batch using pneumatic and mechanical separation in the third unit of the coal preparation shop. Additional increase in the mechanical strength of coke by 1.5-2.0% was predicted with a 0.5-1.0% decrease in wear.

Evaluation of factors affecting ice forces at selected bridges in South Dakota

USGS Publications Warehouse

Niehus, Colin A.

2002-01-01

During 1998-2002, the U.S. Geological Survey, in cooperation with the South Dakota Department of Transportation (SDDOT), conducted a study to evaluate factors affecting ice forces at selected bridges in South Dakota. The focus of this ice-force evaluation was on maximum ice thickness and ice-crushing strength, which are the most important variables in the SDDOT bridge-design equations for ice forces in South Dakota. Six sites, the James River at Huron, the James River near Scotland, the White River near Oacoma/Presho, the Grand River at Little Eagle, the Oahe Reservoir near Mobridge, and the Lake Francis Case at the Platte-Winner Bridge, were selected for collection of ice-thickness and ice-crushing-strength data. Ice thickness was measured at the six sites from February 1999 until April 2001. This period is representative of the climate extremes of record in South Dakota because it included both one of the warmest and one of the coldest winters on record. The 2000 and 2001 winters were the 8th warmest and 11th coldest winters, respectively, on record at Sioux Falls, South Dakota, which was used to represent the climate at all bridges in South Dakota. Ice thickness measured at the James River sites at Huron and Scotland during 1999-2001 ranged from 0.7 to 2.3 feet and 0 to 1.7 feet, respectively, and ice thickness measured at the White River near Oacoma/Presho site during 2000-01 ranged from 0.1 to 1.5 feet. At the Grand River at Little Eagle site, ice thickness was measured at 1.2 feet in 1999, ranged from 0.5 to 1.2 feet in 2000, and ranged from 0.2 to 1.4 feet in 2001. Ice thickness measured at the Oahe Reservoir near Mobridge site ranged from 1.7 to 1.8 feet in 1999, 0.9 to 1.2 feet in 2000, and 0 to 2.2 feet in 2001. At the Lake Francis Case at the Platte-Winner Bridge site, ice thickness ranged from 1.2 to 1.8 feet in 2001. Historical ice-thickness data measured by the U.S. Geological Survey (USGS) at eight selected streamflow-gaging stations in South Dakota were compiled for 1970-97. The gaging stations included the Grand River at Little Eagle, the White River near Oacoma, the James River near Scotland, the James River near Yankton, the Vermillion River near Wakonda, the Vermillion River near Vermillion, the Big Sioux River near Brookings, and the Big Sioux River near Dell Rapids. Three ice-thickness-estimation equations that potentially could be used for bridge design in South Dakota were selected and included the Accumulative Freezing Degree Day (AFDD), Incremental Accumulative Freezing Degree Day (IAFDD), and Simplified Energy Budget (SEB) equations. These three equations were evaluated by comparing study-collected and historical ice-thickness measurements to equation-estimated ice thicknesses. Input data required by the equations either were collected or compiled for the study or were obtained from the National Weather Service (NWS). An analysis of the data indicated that the AFDD equation best estimated ice thickness in South Dakota using available data sources with an average variation about the measured value of about 0.4 foot. Maximum potential ice thickness was estimated using the AFDD equation at 19 NWS stations located throughout South Dakota. The 1979 winter (the coldest winter on record at Sioux Falls) was the winter used to estimate the maximum potential ice thickness. The estimated maximum potential ice thicknesses generally are largest in northeastern South Dakota at about 3 feet and are smallest in southwestern and south-central South Dakota at about 2 feet. From 1999 to 2001, ice-crushing strength was measured at the same six sites where ice thickness was measured. Ice-crushing-strength measurements were done both in the middle of the winter and near spring breakup. The maximum ice-crushing strengths were measured in the mid- to late winter before the spring thaw. Measured ice-crushing strengths were much smaller near spring breakup. Ice-crushing strength measured at the six sites

Investigations into the tensile failure of doubly-convex cylindrical tablets under diametral loading using finite element methodology.

PubMed

Podczeck, Fridrun; Drake, Kevin R; Newton, J Michael

2013-09-15

In the literature various solutions exist for the calculation of the diametral compression tensile strength of doubly-convex tablets and each approach is based on experimental data obtained from single materials (gypsum, microcrystalline cellulose) only. The solutions are represented by complex equations and further differ for elastic and elasto-plastic behaviour of the compacts. The aim of this work was to develop a general equation that is applicable independently of deformation behaviour and which is based on simple tablet dimensions such as diameter and total tablet thickness only. With the help of 3D-FEM analysis the tensile failure stress of doubly-convex tables with central cylinder to total tablet thickness ratios W/D between 0.06 and 0.50 and face-curvature ratios D/R between 0.25 and 1.85 were evaluated. Both elastic and elasto-plastic deformation behaviour were considered. The results of 80 individual simulations were combined and showed that the tensile failure stress σt of doubly-convex tablets can be calculated from σt=(2P/πDW)(W/T)=2P/πDT with P being the failure load, D the diameter, W the central cylinder thickness, and T the total thickness of the tablet. This equation converts into the standard Brazilian equation (σt=2P/πDW) when W equals T, i.e. is equally valid for flat cylindrical tablets. In practice, the use of this new equation removes the need for complex measurements of tablet dimensions, because it only requires values for diameter and total tablet thickness. It also allows setting of standards for the mechanical strength of doubly-convex tablets. The new equation holds both for elastic and elasto-plastic deformation behaviour of the tablets under load. It is valid for all combinations of W/D-ratios between 0.06 and 0.50 with D/R-ratios between 0.00 and 1.85 except for W/D=0.50 in combination with D/R-ratios of 1.85 and 1.43 and for W/D-ratios of 0.40 and 0.30 in combination with D/R=1.85. FEM-analysis indicated a tendency to failure by capping or even more complex failure patterns in these exceptional cases. The FEM-results further indicated that in general W/D-ratios between 0.15 and 0.20 are favourable when the overall size and shape of the tablets is modified to give maximum tablet tensile strength. However, the maximum tensile stress of doubly-convex tablets will never exceed that of a flat-face cylindrical tablet of similar W/D-ratio. The lowest tensile stress depends on the W/D-ratio. For the thinnest central cylinder thickness, this minimum stress occurs at D/R=0.50; for W/D-ratios between 0.10 and 0.20 the D/R-ratio for the minimum tensile stress increases to 0.67, and for all other central cylinder thicknesses the minimum tensile stress is found at D/R=1.00. Copyright © 2013 Elsevier B.V. All rights reserved.

A newly developed lubricant, chitosan laurate, in the manufacture of acetaminophen tablets.

PubMed

Bani-Jaber, Ahmad; Kobayashi, Asuka; Yamada, Kyohei; Haj-Ali, Dana; Uchimoto, Takeaki; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2015-04-10

To study the usefulness of chitosan laurate (CS-LA), a newly developed chitosan salt, as a lubricant, lubrication properties such as the pressure transmission ratio and ejection force were determined at different concentrations of CS-LA in tableting. In addition, tablet properties such as the tensile strength, disintegration time, and dissolution behavior, were also determined. When CS-LA was mixed at concentrations of 0.1%-3.0%, the pressure transmission ratio was increased in a concentration-dependent manner, and the value at a CS-LA concentration of 3% was equal to that of magnesium stearate (Mg-St), a widely used lubricant. Additionally, a reduction in the ejection force was observed at a concentration from 1%, proving that CS-LA has good lubrication performance. A prolonged disintegration time and decreased tensile strength, which are known disadvantages of Mg-St, were not observed with CS-LA. Furthermore, with CS-LA, retardation of dissolution of the drug from the tablets was not observed. Conjugation of CS with LA was found to be quite important for both lubricant and tablet properties. In conclusion, CS-LA should be useful as an alternative lubricant to Mg-St. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

2012-08-01

To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

Pharmacokinetics of Phenobarbital in Microenema Via Macy Catheter Versus Suppository.

PubMed

Lam, Y W Francis; Lam, Ansom; Macy, Brad

2016-06-01

The oral route is compromised for nearly all patients approaching death. When agitation, seizures, or other intractable symptoms occur, a quick, discreet, comfortable, and effective alternate route for medication delivery that is easy to administer in the home setting is highly desirable. To characterize the early absorption profile, variability, and comfort of phenobarbital given in microenema suspensions delivered via the Macy Catheter(®) (MC) vs. the same dose given via suppository. This was a randomized, open-label, crossover study comparing the early absorption profile of equal doses of phenobarbital administered rectally in three treatment phases: phenobarbital suppository and two different microenemas with phenobarbital tablets crushed and suspended in 6 mL (MC-6) or 20 mL (MC-20) of tap water. Mean plasma phenobarbital concentrations at 10 minutes were 12× higher for MC-20 and 8× higher for MC-6 compared to suppository. Concentrations achieved in 30 minutes via MC-20 took almost three hours to achieve with suppository. Mean AUC values were higher for MC-20 and MC-6 (82% and 46%, respectively) vs. suppository (P < 0.05). There was less variability in absorption for MC-20 and MC-6 (1.4- to 1.9-fold difference) compared to a 4.4-fold difference via suppository. MC administrations were reported as "not uncomfortable" compared to suppositories, which were reported as "mildly uncomfortable" (P < 0.05). These results suggest phenobarbital oral tablets crushed and suspended in water and administered via the MC is superior to suppository in delivering the medication reliably and rapidly. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Oil Palm Shell Coarse Aggregate Species on High Strength Lightweight Concrete

PubMed Central

Yew, Ming Kun; Bin Mahmud, Hilmi; Ang, Bee Chin; Yew, Ming Chian

2014-01-01

The objective of this study was to investigate the effects of different species of oil palm shell (OPS) coarse aggregates on the properties of high strength lightweight concrete (HSLWC). Original and crushed OPS coarse aggregates of different species and age categories were investigated in this study. The research focused on two OPS species (dura and tenera), in which the coarse aggregates were taken from oil palm trees of the following age categories (3–5, 6–9, and 10–15 years old). The results showed that the workability and dry density of the oil palm shell concrete (OPSC) increase with an increase in age category of OPS species. The compressive strength of specimen CD3 increases significantly compared to specimen CT3 by 21.8%. The maximum achievable 28-day and 90-day compressive strength is 54 and 56 MPa, respectively, which is within the range for 10–15-year-old crushed dura OPS. The water absorption was determined to be within the range for good concrete for the different species of OPSC. In addition, the ultrasonic pulse velocity (UPV) results showed that the OPS HSLWC attain good condition at the age of 3 days. PMID:24982946

A Comparison of Daily Average Consumption Of Oxycodone Controlled Release (OxyContin CR) And Oxymorphone Extended Release (Opana ER) In Patients With Low Back Pain.

PubMed

Berner, Todd; Thomson, Heather; Hartry, Ann; Puenpatom, R Amy; Ben-Joseph, Rami; Szeinbach, Sheryl L

2011-03-01

Our goal was to examine the daily average consumption (DACON) of oxycodone controlled-release tablets (OxyContin CR)and oxymorphone extended-release tablets (Opana ER) in patients with low back pain. An observational, retrospective cohort study enrolled patients with multiple prescriptions for oxycodone CR or oxymorphone ER tablets. These patients also had International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for low back pain. Pharmacy prescription medication claims data were obtained from a large commercially insured health plan in the U.S. Mean daily consumption was calculated for a 90-day period. We used descriptive statistics to evaluate patient demographics and health plan characteristics. Univariate analyses were used to examine the data as observed. A generalized linear model with a gamma distribution and log-link function provided a sensitivity measure, adjusting for heterogeneity among patients and the skewed nature of the DACON variable. A total of 4,023 patients received oxycodone CR, and 374 patients received oxymorphone ER. The mean age of patients (standard deviation, SD) was 49.0 (11.6) years for oxycodone CR and 47.3 (10.6) years for oxymorphone ER. DACON of oxycodone CR was 3.2 tablets per day, and DACON of oxymorphone ER was 2.7 tablets per day (P < 0.01). Utilization of maximum-strength tablets of oxycodone CR 80 mg was 3.9 tablets per day, which was significantly higher, by one tablet per day, than the utilization of equipotent oxymorphone ER maximum-strength tablets of 40 mg at 2.9 tablets per day (P < 0.01). The use of oxycodone CR, measured as mean daily consumption over a 90-day period, was significantly higher than that for oxymorphone ER in these patients, a finding that could have financial implications for health care systems.

The bending strength of tablets with a breaking line--Comparison of the results of an elastic and a "brittle cracking" finite element model with experimental findings.

PubMed

Podczeck, Fridrun; Newton, J Michael; Fromme, Paul

2015-11-10

The aim of this work was to ascertain the influence of the position of the breaking line of bevel-edged tablets in a three-point bending test. Two different brands of commercially available, flat-round, bevel-edged tablets with a single central breaking line were studied. Breaking line positions tested, relative to the upper loading roll, were 0°, 22.5°, 45°, 67.5° and 90°. The breaking line faced either up- or downwards during the test. The practical results were compared with FEM results simulating similar test configurations. Tablets failed mainly across the failure plane, resulting in two tablet halves. An exception to this was found for tablets where the breaking line faced down and was positioned at an angle of 22.5° relative to the loading plane. Here the crack followed the breaking line in the centre of the tablets and only diverged towards the loading plane position at the edges of the tablets. The breaking line facing upwards resulted in a significantly higher tensile strength of the tablets compared to it facing downwards. However, with one exception, the orientation of the breaking line relative to the loading plane appeared not to affect the tensile strength values. A fully elastic FEM model indicated that both the position of the breaking line relative to the loading plane and as to whether the breaking line faced up- or downwards during the bending test would result in considerably different failure loads during practical experiments. The results also suggested that regardless of the breaking line position, when it is facing down crack propagation should start at the outer edges propagating towards the midpoint of the discs until failure occurs. Failure should hence always result in equal tablet halves, whereby the failure plane should coincide with the loading plane. Neither predictions fully reflected the practical behaviour of the tablets. Using a brittle cracking FEM model significantly larger tensile stresses for tablets with the breaking line positioned downwards at 0° or 22.5° relative to the loading plane were still predicted, but the differences between model and experimental values was greatly reduced. The remaining differences are more likely due to the inadequacy of the equation available to calculate the experimental tensile strength values. This equation cannot account for the presence of a breaking line and overestimates the thickness of the loading plane by the depth of the breaking line when in 0° or 22.5° position. If the depth of the breaking line is taken into account, the model predictions and the experimental findings are comparable. Also, in the brittle cracking FEM simulations the predicted crack propagation patterns were similar to those found in the experiments, and the model stress distributions across the lower surfaces were much more homogeneous and streamlined parallel to the loading plane. The brittle cracking model hence reflected the practicalities of the bending test more closely. The findings suggested that with the breaking line facing down fracture should always start in the centre of a tablet at its lower surface, initiated by the breaking line. Due to simultaneous development of larger stresses along the y-axis the tablet should still break into two equal halves along the loading plane, unless the position of the breaking line relative to the loading plane was 22.5°. In this case the tablet would fail by a mixed process, whereby failure would occur mainly along the breaking line, but due to simultaneous crack formation at the lower surface close to the bevel edge parallel to the loading plane the final breaking pattern would deviate from the breaking line about half-way from its centre, as seen in the practical experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

Levothyroxine soft capsules demonstrate bioequivalent pharmacokinetic exposure with the European reference tablets in healthy volunteers under fasting conditions.

PubMed

Al-Numani, Dina; Scarsi, Claudia; Ducharme, Murray P

2016-02-01

To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.

A study of the properties of tablets made of directly compressible maltose.

PubMed

Muzíková, J; Balhárková, J

2008-01-01

The paper deals with the study of the strength and disintegration time of tablets made of directly compressible maltose Advantose 100. It studies the differences of the effects of two types of lubricants, magnesium stearate and sodium stearylfumarate, on the above-mentioned properties, and it also tests the mixtures of the substance with microcrystalline cellulose Vivapur 102 in a ratio of 1:1 and with ascorbic and acetylsalicylic acids. The compacts are obtained by using three compression forces, excepting mixtures with active ingredients, where one compression force is used. In the compression forces of 6 and 8 kN, no statistically significant difference was found in the intervention of the lubricants into the strength of the compacts made of Advantose 100, only in the compression force of 10 kN Pruv decreased the strength more than stearate. The mixture of Advantose 100 and Vivapur 102 yielded the strongest tablets, an addition of Pruv to it decreased the strength of compacts more than stearate. The periods of disintegration time of Advantose compacts as well as those of the mixture of dry binders were longer with an addition of Pruv. The compacts with acetylsalicylic acid possessed higher strength and a longer period of disintegration than those with ascorbic acid. There was no statistically significant difference within the type of the lubricant employed, both in the case of Advantose 100 and its mixture with Vivapur 102, between the values of strength of the compacts with acetylsalicylic acid.

Effect of a disintegration mechanism on wetting, water absorption, and disintegration time of orodispersible tablets.

PubMed

Pabari, Rm; Ramtoola, Z

2012-07-01

The aim of this study was to evaluate the influence of disintegration mechanism of various types of disintegrants on the absorption ratio (AR), wetting time (WT), and disintegration time (DT) of orodispersible tablets (ODTs). ODTs were prepared by direct compression using mannitol as filler and disintegrants selected from a range of swellable, osmotic, and porous disintegrants. Tablets formed were characterized for their water AR, WT, and DT. The porosity and mechanical strength of the tablets were also measured. Results show that the DT of formulated ODTs was directly related to the WT and was a function of the disintegration mechanism of the disintegrant used. The lowest WT and DT were observed for tablets formulated using the osmotic disintegrant sodium citrate and these tablets also showed the lowest AR and porosity. The wetting and disintegration of tablets containing the highly swellable disintegrant, sodium starch glycollate, was slowest despite their high water AR and high tablet porosity. Rapid wetting and disintegration of ODTs were therefore not necessarily related to the porosity of the tablets.

Effect of Touch Screen Tablet Use on Fine Motor Development of Young Children.

PubMed

Lin, Ling-Yi; Cherng, Rong-Ju; Chen, Yung-Jung

2017-10-20

To investigate the effects of touch-screen tablet use on the fine motor development of preschool children without developmental delay. 40 children who used a touch-screen tablet more 60 minutes per week for at least 1 month received a 24-week home fine motor activity program using a touch-screen-tablet. 40 children matched for age (mean = 61.0 months) and sex who did not meet the criteria for previous tablet use received a 24-week program consisting of manual play activities. Motor performance was measured using the Bruininks-Oseretsky Test of Motor Proficiency. The two-factor mixed design ANOVA was used to compare performance of the touch-screen tablet and non-touch-screen tablet groups. Pretest analysis showed no group differences in motor performance and pinch strength. At posttest, children in the nontouch-screen-tablet group made significantly greater changes in fine motor precision (p < 0.001), fine motor integration (p = 0.008), and manual dexterity (p = 0.003). Using a touch screen tablet extensively might be disadvantageous for the fine motor development of preschool children.

Effect of a Disintegration Mechanism on Wetting, Water Absorption, and Disintegration Time of Orodispersible Tablets

PubMed Central

Pabari, RM; Ramtoola, Z

2012-01-01

The aim of this study was to evaluate the influence of disintegration mechanism of various types of disintegrants on the absorption ratio (AR), wetting time (WT), and disintegration time (DT) of orodispersible tablets (ODTs). ODTs were prepared by direct compression using mannitol as filler and disintegrants selected from a range of swellable, osmotic, and porous disintegrants. Tablets formed were characterized for their water AR, WT, and DT. The porosity and mechanical strength of the tablets were also measured. Results show that the DT of formulated ODTs was directly related to the WT and was a function of the disintegration mechanism of the disintegrant used. The lowest WT and DT were observed for tablets formulated using the osmotic disintegrant sodium citrate and these tablets also showed the lowest AR and porosity. The wetting and disintegration of tablets containing the highly swellable disintegrant, sodium starch glycollate, was slowest despite their high water AR and high tablet porosity. Rapid wetting and disintegration of ODTs were therefore not necessarily related to the porosity of the tablets. PMID:23112534

Inverted drop testing and neck injury potential.

PubMed

Forrest, Stephen; Herbst, Brian; Meyer, Steve; Sances, Anthony; Kumaresan, Srirangam

2003-01-01

Inverted drop testing of vehicles is a methodology that has long been used by the automotive industry and researchers to test roof integrity and is currently being considered by the National Highway Traffic Safety Administration as a roof strength test. In 1990 a study was reported which involved 8 dolly rollover tests and 5 inverted drop tests. These studies were conducted with restrained Hybrid III instrumented Anthropometric Test Devices (ATD) in production and rollcaged vehicles to investigate the relationship between roof strength and occupant injury potential. The 5 inverted drop tests included in the study provided a methodology producing "repeatable roof impacts" exposing the ATDs to the similar impact environment as those seen in the dolly rollover tests. Authors have conducted two inverted drop test sets as part of an investigation of two real world rollover accidents. Hybrid-III ATD's were used in each test with instrumented head and necks. Both test sets confirm that reduction of roof intrusion and increased headroom can significantly enhance occupant protection. In both test pairs, the neck force of the dummy in the vehicle with less crush and more survival space was significantly lower. Reduced roof crush and dynamic preservation of the occupant survival space resulted in only minor occupant contact and minimal occupant loading, establishing a clear causal relationship between roof crush and neck injuries.

An in vitro analysis of disintegration times of different formulations of olanzapine orodispersible tablet: a preliminary report.

PubMed

Hobbs, David; Karagianis, Jamie; Treuer, Tamas; Raskin, Joel

2013-12-01

Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab(®) was included as a non-olanzapine ODT comparator. Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis(®) ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva. The main outcome measure was the disintegration and dissolution characteristics of the ODT formulations. The ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis(®) was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST(®) (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration. Differences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.

Heat and moisture flow in concrete as a function of temperature

NASA Technical Reports Server (NTRS)

Hundt, J.

1978-01-01

Due to temperature, reactors in operation cause heat and moisture flows in the thick walled prestressed pressure vessels. These flows were studied in three beams of concrete made with crushed limestone aggregate, and in three beams made of crushed gravel/sand aggregate. The flow phenomena were related to the structural development of the concrete by determining the amount of non-evaporatable water, the total porosity, and the pore size distribution. Local temperature and moisture conditions also influenced the technical properties. Compressive strength, changes in length due to shrinkage and contraction, thermal expansion, and thermal conductivity were determined.

Effects of some lubricants and evaluation of compression parameters on directly compressible powders.

PubMed

Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

2014-05-01

The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant "Hexagonal boron nitride (HBN)" on direct compression powders. Lubricants such as magnesium stearate, glyceryl behenate, stearic acid, talc and polyethylene glycol6000 were studied in this article. Tablets were manufactured on an instrumented tablet press with various lubricant concentrations. Bulk and tapped densities, and Carr's index parameters were calculated for powders. Tensile strength, cohesion index, lower punch ejection force and lubricant effectiveness values were investigated for tablets. The deformation mechanisms of tablets were studied during compression from the Heckel plots with or without lubricants. Powders formulated with MGST and HBN showed better flow properties based on Carr's index. MGST was found to be the most effective lubricant based on lubricant effectiveness for tablets. HBN was found very close to MGST with the same concentrations. Other lubricants showed less effectiveness than that of MGST and HBN. It is observed that an increase in the concentration of HBN leads to decreased tensile strength and cohesion index values because of its surface-covering property. Despite covering property, HBN had no significant effect on disintegration time. Based on the Heckel plots at the level of 1%, HBN showed the most pronounced plastic character.

An evaluation of bituminized fiber pipe culverts.

DOT National Transportation Integrated Search

1970-01-01

This report describes the results to date in a limited study, including laboratory tests and field evaluations, of the suitability of bituminized fiber pipe for use as highway culverts. Crushing strength data obtained from three-edge bearing tests in...

Evaluation and Comparison of Three Types of Spray Dried Coprocessed Excipient Avicel® for Direct Compression

PubMed Central

Solný, Tomaš

2018-01-01

As coprocessed excipients (CPE) gain a lot of focus recently, this article compares three commercially available CPE of Avicel brand, namely, CE 15, DG, and HFE 102. Comparison is based on measured physical properties of coprocessed mixtures, respectively, flow properties, pycnometric density, mean particle size, specific surface area, moisture content, hygroscopicity, solubility, pH leaching, electrostatic charge, SEM images, and DSC. Tablets were made employing three pressure sets. Viscoelastic properties and ejection force were assessed during compression, as well as pycnometric density, mass uniformity, height, tensile strength, friability, disintegration, and wetting times. Avicel CE 15 is of mid-range flow properties, contains mid-size and nonspherical particles, and has high hygroscopicity, growing negative charge, best lubricity, lowest tensile strength, and mid-long disintegration times. Avicel DG possesses the worst flow properties, small asymmetrical particles, lowest hygroscopicity, stable charge, intermediate lubricity, and tensile strength and exhibits fast disintegration of tablets. Finally, Avicel HFE 102 has the best flow properties, large symmetrical particles, and middle hygroscopicity and its charge fluctuates throughout blending. It also exhibits inferior lubricity, the highest tensile strength, and slow disintegration of tablets. Generally, it is impossible to select the best CPE, as their different properties fit versatile needs of countless manufacturers and final products. PMID:29850496

Pharmacokinetics of three formulations of ondansetron hydrochloride in healthy volunteers: 24-mg oral tablet, rectal suppository, and i.v. infusion.

PubMed

VanDenBerg, C M; Kazmi, Y; Stewart, J; Weidler, D J; Tenjarla, S N; Ward, E S; Jann, M W

2000-06-01

The absolute bioavailability and pharmacokinetics of three formulations of ondansetron hydrochloride 24 mg--an oral tablet, an intravenous solution, and an extemporaneous rectal suppository--were studied. Twelve healthy, nonsmoking volunteers (six men and six women) were given ondansetron in a study with a three-way cross-over design. All subjects received each dosage form on the same day in the following order: oral tablet, rectal suppository, and intravenous infusion. Administrations were separated by one week. Blood sampling times varied, depending on the administration route. Mean absolute bioavailability for the oral tablet and the rectal suppository differed significantly. Absorption of ondansetron was prolonged when it was administered as the rectal suppository. Absolute bioavailability for the 24-mg tablet was similar to that for other tablet strengths in previous studies. All subjects completed the study without significant adverse effects. Absorption of ondansetron from the rectal suppository was prolonged compared with the oral tablet and the i.v. infusion. Bioavailability for the 24-mg suppository formulation was considerably lower than for the 24-mg tablet.

Laser Printing of PCL/Progesterone Tablets for Drug Delivery Applications in Hormone Cancer Therapy

NASA Astrophysics Data System (ADS)

Salmoria, G. V.; Klauss, P.; Kanis, L. A.

2017-09-01

In this study, polycaprolactone (PCL) and progesterone (PG) tablets were produced by selective laser sintering (SLS) using different particle sizes and laser energy. The sintered PCL/PG tablets presented uniform morphology, coalescence of particles and interconnected pores distributed in the polymeric matrix. The EDS analysis confirmed the presence of progesterone recrystallized on the surface of the porous PCL matrix. The crystallinity values for the PCL/PG tablets were lower than that for the pure PCL, suggesting the interaction of components at the molecular level. The PCL/PG tablets fabricated with small particles and high laser energy presented a higher value for the flexural modulus compared with the other specimens. The glass transition temperature (Tg) was -37 °C for the PCL/PG tablet with a high degree of sintering. The fatigue test showed that the PCL/PG blend tablets have high fatigue strength. The drug release mechanism of all tablets studied followed a zero-order kinetics, and drug release rates were dependent on sintering degree and, consequently, on matrix erosion, showing a potential application to controlled drug delivery in hormone cancer therapy.

Effect of fly ash on properties of crushed brick and reclaimed asphalt in pavement base/subbase applications.

PubMed

Mohammadinia, Alireza; Arulrajah, Arul; Horpibulsuk, Suksun; Chinkulkijniwat, Avirut

2017-01-05

Fly Ash (FA), an abundant by-product with no carbon footprint, is a potential stabilizer for enhancing the physical and geotechnical properties of pavement aggregates. In this research, FA was used in different ratios to stabilize crushed brick (CB) and reclaimed asphalt pavement (RAP) for pavement base/subbase applications. The FA stabilization of CB and RAP was targeted to improve the strength and durability of these recycled materials for pavement base/subbase applications. The Unconfined Compressive Strength (UCS) and resilient modulus (M R ) development of the stabilized CB and RAP aggregates was studied under room temperature and at an elevated temperatures of 40°C, and results compared with unbound CB and RAP. Analysis of atomic silica content showed that when the amount of silica and alumina crystalline was increased, the soil structure matrix deteriorated, resulting in strength reduction. The results of UCS and M R testing of FA stabilized CB and RAP aggregates indicated that FA was a viable binder for the stabilization of recycled CB and RAP. CB and RAP stabilized with 15% FA showed the highest UCS results at both room temperature and at 40°C. Higher temperature curing was also found to result in higher strengths. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Earl D Mattson; Ghanashyam Neupane; Mitchell Plummer

Long-term sustainability of fracture conductivity is critical for commercial success of engineered geothermal system (EGS) and hydrogeothermal field sites. The injection of proppants has been suggested as a means to enhance the conductivity in these systems. Several studies have examined the chemical behavior of proppants that are not at chemical equilibrium with the reservoir rock and water. These studies have suggested that in geothermal systems, geochemical reactions can lead to enhance proppant dissolution and deposition alteration minerals. We hypothesize that proppant dissolution will decrease the strength of the proppant and can potentially reduce the conductivity of the fracture. To examinemore » the geomechanical strength of proppants, we have performed modified crushing tests of proppants and reservoir rock material that was subjected to geothermal reservoir temperature conditions. The batch reactor experiments heated crushed quartz monzonite rock material, proppants (either quartz sand, sintered bauxite or kryptospheres) with Raft River geothermal water to 250 ºC for a period of 2 months. Solid and liquid samples were shipped to University of Utah for chemical characterization with ICP-OES, ICP-MS, and SEM. A separate portion of the rock/proppant material was subjected to a modified American Petroleum Institute ISO 13503-2 proppant crushing test. This test is typically used to determine the maximum stress level that can be applied to a proppant pack without the occurrence of unacceptable proppant crushing. We will use the test results to examine potential changes in proppant/reservoir rock geomechanical properties as compared to samples that have not been subjected to geothermal conditions. These preliminary results will be used to screen the proppants for long term use in EGS and hot hydrogeothermal systems.« less

Performance of geogrid reinforced ballast under dynamic loading.

DOT National Transportation Integrated Search

2012-07-01

Railroad ballast consists of open graded crushed stone used as a bed for railroad track to provide stability. Over time, : ballast degrades and loses its strength. Fouling of ballast with fines has been a major issue of railway engineering. In this :...

Improvement of Physico-mechanical Properties of Partially Amorphous Acetaminophen Developed from Hydroalcoholic Solution Using Spray Drying Technique

PubMed Central

Sadeghi, Fatemeh; Torab, Mansour; Khattab, Mostafa; Homayouni, Alireza; Afrasiabi Garekani, Hadi

2013-01-01

Objective(s): This study was performed aiming to investigate the effect of particle engineering via spray drying of hydroalcoholic solution on solid states and physico-mechanical properties of acetaminophen. Materials and Methods: Spray drying of hydroalcoholic solution (25% v/v ethanol/water) of acetaminophen (5% w/v) in the presence of small amounts of polyninylpyrrolidone K30 (PVP) (0, 1.25, 2.5 and 5% w/w based on acetaminophen weight) was carried out. The properties of spray dried particles namely morphology, surface characteristics, particle size, crystallinity, dissolution rate and compactibility were evaluated. Results: Spray drying process significantly changed the morphology of acetaminophen crystals from acicular (rod shape) to spherical microparticle. Differential scanning calorimetery (DSC) and x-ray powder diffraction (XRPD) studies ruled out any polymorphism in spray dried samples, however, a major reduction in crystallinity up to 65%, especially for those containing 5% w/w PVP was observed. Spray dried acetaminophen particles especially those obtained in the presence of PVP exhibited an obvious improvement of the dissolution and compaction properties. Tablets produced from spray dried samples exhibited excellent crushing strengths and no tendency to cap. Conclusions: The findings of this study revealed that spray drying of acetaminophen from hydroalcoholic solution in the presence of small amount of PVP produced partially amorphous particles with improved dissolution and excellent compaction properties. PMID:24379968

The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance.

PubMed

van den Ban, Sander; Goodwin, Daniel J

2017-05-01

The impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process. Granules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility. Tabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability. The method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.

Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters.

PubMed

Kanani, Kunal; Gatoulis, Sergio C; Voelker, Michael

2015-08-03

Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer's clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

PubMed Central

Kanani, Kunal; Gatoulis, Sergio C.; Voelker, Michael

2015-01-01

Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters. PMID:26247959

INFLUENCE OF TABLET SPLITTING ON CONTENT UNIFORMITY OF LISINOPRIL/ HYDROCHLORTHIAZIDE TABLETS

PubMed Central

Vranić, Edina; Uzunović, Alija

2007-01-01

Dose-related adverse effects of medications are a major problem in modern medical practice. The “correct” dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril-hydrochlorothiazide scored tablets labeled to contain 20/12,5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12,5 mg in the whole tablet) were: 49,60 ±3,29% and 49,29±0,60 % (lisinopril); 50,33±3,50% and 50,69±1,95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy PMID:18039191

Relationships between response surfaces for tablet characteristics of placebo and API-containing tablets manufactured by direct compression method.

PubMed

Hayashi, Yoshihiro; Tsuji, Takahiro; Shirotori, Kaede; Oishi, Takuya; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

2017-10-30

In this study, we evaluated the correlation between the response surfaces for the tablet characteristics of placebo and active pharmaceutical ingredient (API)-containing tablets. The quantities of lactose, cornstarch, and microcrystalline cellulose were chosen as the formulation factors. Ten tablet formulations were prepared. The tensile strength (TS) and disintegration time (DT) of tablets were measured as tablet characteristics. The response surfaces for TS and DT were estimated using a nonlinear response surface method incorporating multivariate spline interpolation, and were then compared with those of placebo tablets. A correlation was clearly observed for TS and DT of all APIs, although the value of the response surfaces for TS and DT was highly dependent on the type of API used. Based on this knowledge, the response surfaces for TS and DT of API-containing tablets were predicted from only two and four formulations using regression expression and placebo tablet data, respectively. The results from the evaluation of prediction accuracy showed that this method accurately predicted TS and DT, suggesting that it could construct a reliable response surface for TS and DT with a small number of samples. This technique assists in the effective estimation of the relationships between design variables and pharmaceutical responses during pharmaceutical development. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of drug release and tablet characteristics of silicone adhesive matrix tablets.

PubMed

Tolia, Gaurav; Li, S Kevin

2012-11-01

Matrix tablets of a model drug acetaminophen (APAP) were prepared using a highly compressible low glass transition temperature (T(g)) polymer silicone pressure sensitive adhesive (PSA) at various binary mixtures of silicone PSA/APAP ratios. Matrix tablets of a rigid high T(g) matrix forming polymer ethyl cellulose (EC) were the reference for comparison. Drug release study was carried out using USP Apparatus 1 (basket), and the relationship between the release kinetic parameters of APAP and polymer/APAP ratio was determined to estimate the excipient percolation threshold. The critical points attributed to both silicone PSA and EC tablet percolation thresholds were found to be between 2.5% and 5% w/w. For silicone PSA tablets, satisfactory mechanical properties were obtained above the polymer percolation threshold; no cracking or chipping of the tablet was observed above this threshold. Rigid EC APAP tablets showed low tensile strength and high friability. These results suggest that silicone PSA could eliminate issues related to drug compressibility in the formulation of directly compressed oral controlled release tablets of poorly compressible drug powder such as APAP. No routinely used excipients such as binders, granulating agents, glidants, or lubricants were required for making an acceptable tablet matrix of APAP using silicone PSA. Copyright © 2012 Elsevier B.V. All rights reserved.

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

PubMed

Hamer, Ann M; Hartung, Daniel M; Haxby, Dean G; Ketchum, Kathy L; Pollack, David A

2006-01-01

One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.

Adsorption of Se species on crushed granite: a direct linkage with its internal iron-related minerals.

PubMed

Jan, Yi-Lin; Wang, Tsing-Hai; Li, Ming-Hsu; Tsai, Shih-Chin; Wei, Yuan-Yaw; Teng, Shi-Ping

2008-01-01

The adsorption of selenium species on crushed granite is investigated directly linking to its internal iron-related minerals. Experimental results demonstrated that granite has higher affinity toward Se(IV) adsorption than Se(VI) adsorption. Se(IV) adsorption on granite is insensitive to background electrolytes while the effect of ionic strength on Se(VI) adsorption is not observed, which is attributed to the overloading of Se(VI) ions. Results of chemical sequential extraction showed that the removal of crystalline iron oxides dramatically reduces Se(IV) adsorption, which corresponds to the disappearance of goethite signal within XRD pattern. Based on our results, it is proposed that goethite within granite dominates Se adsorption in crushed granite. Although these goethites probably stem from some sample preparation processes including drilling in situ, crushing, washing and drying granite samples in laboratory, the formation of goethite enhances the granite affinity toward Se species adsorption. Images of SEM/EDS furthermore revealed that goethite is embedded within the fractures. In addition, quantification by standard addition method by spiking goethite suspension indicates that only around 20% of goethite minerals are available during Se(IV) adsorption.

Effect of the variation in the ambient moisture on the compaction behavior of powder undergoing roller-compaction and on the characteristics of tablets produced from the post-milled granules.

PubMed

Gupta, Abhay; Peck, Garnet E; Miller, Ronald W; Morris, Kenneth R

2005-10-01

Effect of variation in the ambient moisture levels on the compaction behavior of a 10% acetaminophen (APAP) powder blend in microcrystalline cellulose (MCC) powder was studied by comparing the physical and mechanical properties of ribbons prepared by roller compaction with those of simulated ribbons, i.e., tablets prepared under uni-axial compression. Relative density, moisture content, tensile strength, and Young's modulus were used as key compact properties for comparison. Moisture was found to facilitate the particle rearrangement of both, the APAP and the MCC particles, as well as the deformation of the MCC particles. The tensile strength of the simulated ribbons also showed an increase with increasing moisture content. An interesting observation was that the tensile strength of the roller compacted samples first increased and then decreased with increasing moisture content. Variation in the ambient moisture during roller compaction was also found to influence the characteristics of tablets produced from the granules obtained post-milling the ribbons. A method to study this influence is also reported. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Development and evaluation of novel lozenges containing marshmallow root extract.

PubMed

Benbassat, Niko; Kostova, Bistra; Nikolova, Irina; Rachev, Dimitar

2013-11-01

Lozenges (tablets intended to be dissolved slowly in the mouth) were evaluated as delivery system for polysaccharides extract from Althaea officinalis L. (marshmallow) root. The aim of investigation was to improve of the efficacy of convenient preparations for the treatment of irritated oropharyngeal mucosa and associated dry irritable cough. The formulations studied were prepared with water extract of roots of Althaea officinalis L. The polysaccharides extract was obtained by ultrasonification. Acute oral toxicity (LD 50 p.o.) of the obtained extract was estimated in mice. Four models of lozenges based on different excipients were formulated. The characteristics of the preparations: resistance to crushing, friability testing, disintegration time and drug release properties were evaluated.

In Vitro Evaluation of Eslicarbazepine Delivery via Enteral Feeding Tubes.

PubMed

Reindel, Kristin; Zhao, Fang; Hughes, Susan; Dave, Vivek S

2017-12-01

Purpose: The feasibility of preparing an eslicarbazepine acetate suspension using Aptiom tablets for administration via enteral feeding tubes was evaluated. Methods: Eslicarbazepine acetate suspension (40 mg/mL) was prepared using Aptiom tablets after optimizing the tablet crushing methods and the vehicle composition. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to monitor the eslicarbazepine stability in the prepared suspension. Three enteric feeding tubes of various composition and dimensions were evaluated for the delivery of the suspensions. The suspension was evaluated for the physical and chemical stability for 48 hours. Results: The reproducibility and consistency of particle size reduction was found to be best with standard mortar/pestle. The viscosity analysis and physical stability studies showed that ORA-Plus:water (50:50 v/v) was optimal for suspending ability and flowability of suspension through the tubes. The developed HPLC method was found to be stability indicating and suitable for the assay of eslicarbazepine acetate in the prepared suspension. The eslicarbazepine concentrations in separately prepared suspensions were within acceptable range (±3%), indicating accuracy and reproducibility of the procedure. The eslicarbazepine concentrations in suspensions before and after delivery through the enteric feeding tubes were within acceptable range (±4%), indicating absence of any physical/chemical interactions of eslicarbazepine with the tubes and a successful delivery of eslicarbazepine dosage via enteric feeding tubes. The stability study results showed that eslicarbazepine concentration in the suspension remained unchanged when stored at room temperature for 48 hours. Conclusion: The study presents a convenient procedure for the preparation of a stable suspension of eslicarbazepine acetate (40 mg/mL) using Aptiom tablets, for administration via enteral feeding tubes.

Combining experimental design and orthogonal projections to latent structures to study the influence of microcrystalline cellulose properties on roll compaction.

PubMed

Dumarey, Melanie; Wikström, Håkan; Fransson, Magnus; Sparén, Anders; Tajarobi, Pirjo; Josefson, Mats; Trygg, Johan

2011-09-15

Roll compaction is gaining importance in pharmaceutical industry for the dry granulation of heat or moisture sensitive powder blends with poor flowing properties prior to tabletting. We studied the influence of microcrystalline cellulose (MCC) properties on the roll compaction process and the consecutive steps in tablet manufacturing. Four dissimilar MCC grades, selected by subjecting their physical characteristics to principal components analysis, and three speed ratios, i.e. the ratio of the feed screw speed and the roll speed of the roll compactor, were included in a full factorial design. Orthogonal projection to latent structures was then used to model the properties of the resulting roll compacted products (ribbons, granules and tablets) as a function of the physical MCC properties and the speed ratio. This modified version of partial least squares regression separates variation in the design correlated to the considered response from the variation orthogonal to that response. The contributions of the MCC properties and the speed ratio to the predictive and orthogonal components of the models were used to evaluate the effect of the design variation. The models indicated that several MCC properties, e.g. bulk density and compressibility, affected all granule and tablet properties, but only one studied ribbon property: porosity. After roll compaction, Ceolus KG 1000 resulted in tablets with obvious higher tensile strength and lower disintegration time compared to the other MCC grades. This study confirmed that the particle size increase caused by roll compaction is highly responsible for the tensile strength decrease of the tablets. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of Coprocessed Chitin-Calcium Carbonate as Multifunctional Tablet Excipient for Direct Compression.

PubMed

Chaheen, Mohammad; Sanchez-Ballester, Noelia M; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

2018-04-24

Owing to the increasing interest in multifunctional excipients for tableting, coprocessing of individual excipients is regularly used to produce excipients of improved multifunctionality superior to individual excipients or their physical mix. The use of chitin as an excipient in tablet formulation is limited because of certain drawbacks such as poor flowability and low true density. The objective of this work is to improve these properties through coprocessing of chitin with calcium carbonate (CaCO 3 ) by precipitating CaCO 3 on chitin particles using different methods. In addition, optimization of the coprocessed chitin was carried out to improve the excipient's properties. Physicochemical (CaCO 3 content, true density, X-ray diffraction, infrared spectroscopy, and scanning electron microscopy) and functional testing (swelling force, flowability, tensile strength, deformation mechanism, and disintegration time) were used to characterize the coprocessed product. Results showed that the calcite CaCO 3 polymorph is precipitated on the chitin surface and that it interacts with chitin at carbonyl- and amide-group level. In addition, the coprocessed excipient has an improved true density and powder flowability, with CaCO 3 forming single layer on the chitin particles surface. Tableting studies showed that the coprocessed powder exhibited an intermediate deformation behavior between CaCO 3 (most brittle) and chitin (most plastic). Tablets showed acceptable tensile strength and rapid disintegration (2-4 s). These results show the potential use of coprocessed chitin-CaCO 3 as a multifunctional excipient for fast disintegration of tablets produced by direct compression. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Stability of Dihydroartemisinin-Piperaquine Tablet Halves During Prolonged Storage Under Tropical Conditions.

PubMed

Hodel, Eva Maria; Kaur, Harparkash; Terlouw, Dianne J

2017-02-08

Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens involve breaking tablets into halves to accurately dose children according to body weight. Use of tablet fractions in programmatic settings under tropical conditions requires a highly stable product; however, the stability of DP tablet fractions is unknown. We aged full and half DP (Eurartesim ® ) tablets in a stability chamber at 30°C and 70% humidity level. The active pharmaceutical ingredients dihydroartemisinin and piperaquine remained at ≥ 95% over the 3 months' period of ageing in light and darkness. These findings are reassuring for DP, but highlight the need to assess drug stability under real-life settings during the drug development process, particularly for key drugs of global disease control programs. © The American Society of Tropical Medicine and Hygiene.

On collisional disruption - Experimental results and scaling laws

NASA Technical Reports Server (NTRS)

Davis, Donald R.; Ryan, Eileen V.

1990-01-01

Both homogeneous and inhomogeneous targets have been addressed by the present experimental consideration of the impact strengths, fragment sizes, and fragment velocities generated by cement mortar targets whose crushing strengths vary by an order of magnitude, upon impact of projectiles in the velocity range of 50-5700 m/sec. When combined with additional published data, dynamic impact strength is found to correlate with quasi-static material strengths for materials ranging in character from basalt to ice; two materials not following this trend, however, are weak mortar and clay targets. Values consistent with experimental results are obtainable with a simple scaling algorithm based on impact energy, material properties, and collisional strain rate.

A new approach combining different MRI methods to provide detailed view on swelling dynamics of xanthan tablets influencing drug release at different pH and ionic strength.

PubMed

Mikac, Ursa; Sepe, Ana; Kristl, Julijana; Baumgartner, Sasa

2010-08-03

The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. We have selected magnetic resonance imaging (MRI) as the method of choice for visualizing the dynamic processes occurring during the swelling of xanthan tablets in a variety of media. The aims were (i) to develop a new method using MRI for accurate determination of penetration, swelling and erosion fronts, (ii) to investigate the effects of pH and ionic strength on swelling, and (iii) to study the influence of structural changes in xanthan gel on drug release. Two dimensional (2D) MRI and one dimensional single point imaging (SPI) of swollen xanthan tablets were recorded, together with T(2) mapping. The border between dry and hydrated glassy xanthan-the penetration front-was determined from 1D SPI signal intensity profiles. The erosion front was obtained from signal intensity profiles of 2D MR images. The swelling front, where xanthan is transformed from a glassy to a rubbery state (gel formation), was determined from T(2) profiles. Further, the new combination of MRI methods for swelling front determination enables to explain the appearance of the unusual "bright front" observed on 2D MR images in tablets swollen in HCl pH 1.2 media, which represents the position of swelling front. All six media studied, differing in pH and ionic strength, penetrate through the whole tablet in 4h+/-0.3h, but formation of the gel layer is significantly delayed. Unexpectedly, the position of the swelling front was the same, independently of the different xanthan gel structures formed under different conditions of pH and ionic strength. The position of the erosion front, on the other hand, is strongly dependent on pH and ionic strength, as reflected in different thicknesses of the gel layers. The latter are seen to be the consequence of the different hydrodynamic radii of the xanthan molecules, which affect the drug release kinetics. The slowest release of pentoxifylline was observed in water where the thickest gel was formed, whereas the fastest release was observed in HCl pH 1.2, in which the gel layer was thinnest. Moreover, experiments simulating physiological conditions showed that changes of pH and ionic strength influence the xanthan gel structure relatively quickly, and consequently the drug release kinetics. It is therefore concluded that drug release is greatly influenced by changes in the xanthan molecular conformation, as reflected in changed thickness of the gel layer. A new method utilizing combination of SPI, multi-echo MRI and T(2) mapping eliminates the limitations of standard methods used in previous studies for determining moving fronts and improves current understanding of the dynamic processes involved in polymer swelling. Copyright (c) 2010 Elsevier B.V. All rights reserved.

[Study of mixed dry binders in directly compressible lactoses and microcrystalline cellulose].

PubMed

Muzíková, J; Vinklarová, S

2004-09-01

The paper evaluated the compressibility of dry binders prepared in the ratios of 3:1, 1:1, and 1:3 from Pharmatosa DCL 15 and DCL 21 and Avicel PH 200, and the sensitivity of the mixtures to an addition of the lubricant magnesium stearate from the standpoint of the effect on the strength of tablets. Mixtures of lactoses with Avicel PH -200 in a ratio of 3:1 proved to be most advantageous. The strengths of tablets made of these mixtures oscillated in the optimal range and they showed the least sensitivity to the added lubricant. An increase in stearate concentration did not result in a marked decrease in the strength of compacts. Pharmatosa DCL 21 in a mixture with Avicel PH 200 yielded stronger compacts at lower compression force than Pharmatosa DCL 15.

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

PubMed

Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

2016-03-01

Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory guidance should be reevaluated to assure consistent safety and efficacy among different strengths.

Metal-Matrix/Hollow-Ceramic-Sphere Composites

NASA Technical Reports Server (NTRS)

Baker, Dean M.

2011-01-01

A family of metal/ceramic composite materials has been developed that are relatively inexpensive, lightweight alternatives to structural materials that are typified by beryllium, aluminum, and graphite/epoxy composites. These metal/ceramic composites were originally intended to replace beryllium (which is toxic and expensive) as a structural material for lightweight mirrors for aerospace applications. These materials also have potential utility in automotive and many other terrestrial applications in which there are requirements for lightweight materials that have high strengths and other tailorable properties as described below. The ceramic component of a material in this family consists of hollow ceramic spheres that have been formulated to be lightweight (0.5 g/cm3) and have high crush strength [40.80 ksi (.276.552 MPa)]. The hollow spheres are coated with a metal to enhance a specific performance . such as shielding against radiation (cosmic rays or x rays) or against electromagnetic interference at radio and lower frequencies, or a material to reduce the coefficient of thermal expansion (CTE) of the final composite material, and/or materials to mitigate any mismatch between the spheres and the matrix metal. Because of the high crush strength of the spheres, the initial composite workpiece can be forged or extruded into a high-strength part. The total time taken in processing from the raw ingredients to a finished part is typically 10 to 14 days depending on machining required.

Investigating the effect of tablet thickness and punch curvature on density distribution using finite elements method.

PubMed

Diarra, Harona; Mazel, Vincent; Busignies, Virginie; Tchoreloff, Pierre

2015-09-30

Finite elements method was used to study the influence of tablet thickness and punch curvature on the density distribution inside convex faced (CF) tablets. The modeling of the process was conducted on 2 pharmaceutical excipients (anhydrous calcium phosphate and microcrystalline cellulose) by using Drucker-Prager Cap model in Abaqus(®) software. The parameters of the model were obtained from experimental tests. Several punch shapes based on industrial standards were used. A flat-faced (FF) punch and 3 convex faced (CF) punches (8R11, 8R8 and 8R6) with a diameter of 8mm were chosen. Different tablet thicknesses were studied at a constant compression force. The simulation of the compaction of CF tablets with increasing thicknesses showed an important change on the density distribution inside the tablet. For smaller thicknesses, low density zones are located toward the center. The density is not uniform inside CF tablets and the center of the 2 faces appears with low density whereas the distribution inside FF tablets is almost independent of the tablet thickness. These results showed that FF and CF tablets, even obtained at the same compression force, do not have the same density at the center of the compact. As a consequence differences in tensile strength, as measured by diametral compression, are expected. This was confirmed by experimental tests. Copyright © 2015 Elsevier B.V. All rights reserved.

The Effects of Triggering Mechanisms on the Energy Absorption Capability of Circular Jute/Epoxy Composite Tubes under Quasi-Static Axial Loading

NASA Astrophysics Data System (ADS)

Sivagurunathan, Rubentheran; Lau Tze Way, Saijod; Sivagurunathan, Linkesvaran; Yaakob, Mohd. Yuhazri

2018-01-01

The usage of composite materials have been improving over the years due to its superior mechanical properties such as high tensile strength, high energy absorption capability, and corrosion resistance. In this present study, the energy absorption capability of circular jute/epoxy composite tubes were tested and evaluated. To induce the progressive crushing of the composite tubes, four different types of triggering mechanisms were used which were the non-trigger, single chamfered trigger, double chamfered trigger and tulip trigger. Quasi-static axial loading test was carried out to understand the deformation patterns and the load-displacement characteristics for each composite tube. Besides that, the influence of energy absorption, crush force efficiency, peak load, mean load and load-displacement history were examined and discussed. The primary results displayed a significant influence on the energy absorption capability provided that stable progressive crushing occurred mostly in the triggered tubes compared to the non-triggered tubes. Overall, the tulip trigger configuration attributed the highest energy absorption.

Fresh and mechanical properties of self-compacting concrete with coarse aggregate replacement using Waste of Oil Palm Shell

NASA Astrophysics Data System (ADS)

Prayuda, Hakas; Saleh, Fadillawaty; Ilham Maulana, Taufiq; Monika, Fanny

2018-05-01

Self-compacting Concrete (SCC) is a real innovation that can solidify itself without the help of tools to ease field practice. In its implementation, SCC can use alternative materials to reduce waste, such as Oil Palm Shell (OPS). In this research, OPS used as a replacement of crushed stone as the main coarse aggregate. The concrete mixture used consists of cement, sand, crushed stone, OPS as a variation of aggregate substitutes, palm oil fuel ash, and superplasticizer. OPS used were variated with 0%, 5%, 10%, 25% and 50% of crushed stone aggregate weight with age up to 28 days. Tests were conducted on fresh and mechanical properties. From the results, it is known that replacement of aggregate using OPS meets fresh properties criteria and although the compressive strength of OPS concrete mixture is lower than normal SCC, OPS still can be an alternative in making SCC and reducing palm oil industrial waste.

Physicochemical characterisation of fluids and soft foods frequently mixed with oral drug formulations prior to administration to children.

PubMed

Kersten, E; Barry, A; Klein, S

2016-03-01

Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development.

The Soy Isoflavones to Reduce Bone Loss (SIRBL) Study: Three Year Effects on pQCT Bone Mineral Density and Strength Measures in Postmenopausal Women

USDA-ARS?s Scientific Manuscript database

Soy isoflavones exert inconsistent bone density preserving effects, but the bone strength preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength ...

Optimization of HS-SPME/GC-MS analysis and its use in the profiling of illicit ecstasy tablets (Part 1).

PubMed

Bonadio, Federica; Margot, Pierre; Delémont, Olivier; Esseiva, Pierre

2009-05-30

A headspace solid-phase microextraction procedure (HS-SPME) was developed for the profiling of traces present in 3,4-methylenedioxymethylampethamine (MDMA). Traces were first extracted using HS-SPME and then analyzed by gas chromatography-mass spectroscopy (GC-MS). The HS-SPME conditions were optimized using varying conditions. Optimal results were obtained when 40 mg of crushed MDMA sample was heated at 80 degrees C for 15 min, followed by extraction at 80 degrees C for 15 min with a polydimethylsiloxane/divinylbenzene coated fibre. A total of 31 compounds were identified as traces related to MDMA synthesis, namely precursors, intermediates or by-products. In addition some fatty acids used as tabletting materials and caffeine used as adulterant, were also detected. The use of a restricted set of 10 target compounds was also proposed for developing a screening tool for clustering samples having close profile. 114 seizures were analyzed using an SPME auto-sampler (MultiPurpose Samples MPS2), purchased from Gerstel GMBH & Co. (Germany), and coupled to GC-MS. The data was handled using various pre-treatment methods, followed by the study of similarities between sample pairs based on the Pearson correlation. The results show that HS-SPME, coupled with the suitable statistical method is a powerful tool for distinguishing specimens coming from the same seizure and specimens coming from different seizures. This information can be used by law enforcement personnel to visualize the ecstasy distribution network as well as the clandestine tablet manufacturing.

Development of an extemporaneous oral liquid formulation of oxandrolone and its stability evaluation.

PubMed

Garg, Alka; Garg, Sanjay; She, Richard Wong

2011-11-01

Many references exist in the literature identifying the usefulness of oxandrolone in treating muscle wasting due to various conditions including severe burns. However, there is an absence of dosage form alternatives as it is only available as tablets. The dose for children is weight based (0.1 mg/kg) which is difficult to achieve with the currently available tablets of 2.5 mg and 10 mg. The literature provides ample evidence of clinical importance but little guidance on extemporaneous oral liquid formulation of oxandrolone. In order to develop and validate an extemporaneous liquid formulation, suspensions of oxandrolone were developed using locally available (New Zealand) vehicles. Combinations of these vehicles with ethanol, as advised in some articles were also tried. Assay method was developed for oxandrolone using High Performance Liquid Chromatography (HPLC) and Mass Spectroscopy (LC-MS). The formulations were evaluated for stability as per the International Conference on Harmonization (ICH) stability guidelines. They were observed for physical and chemical stability at different time points over a period of 28 days. A stable and validated liquid formulation of oxandrolone has been developed which can be made under the hospital and community pharmacy conditions. The formula utilises commercially available oxandrolone tablets, crushed and dispersed in Simple Syrup BP or Orablend(®) vehicle. The formulation has confirmed stability for 21 days and can be easily made with locally available vehicles. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Transbuccal delivery of betahistine dihydrochloride from mucoadhesive tablets with a unidirectional drug flow: in vitro, ex vivo and in vivo evaluation

PubMed Central

El-Nabarawi, Mohamed A; Ali, Adel A; Aboud, Heba M; Hassan, Amira H; Godah, Amany H

2016-01-01

Objective Betahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of Ménière’s disease, undergoes extensive first-pass metabolism and suffers from short biological half-life. The aim of the present work was to develop and estimate controlled release mucoadhesive buccal tablets of BH.2HCl with a unidirectional drug flow to overcome this encumbrance. Methods A direct compression method was adopted for preparation of the tablets using mucoadhesive polymers like guar gum, hydroxypropyl methyl cellulose K4M, sodium carboxymethyl cellulose and their combinations. The tablets were coated from all surfaces except one surface with a solution of 5% (w/v) cellulose acetate and 1% (w/v) dibutyl phthalate. Different permeation enhancers like 2% sodium deoxycholate, 2% sodium cholate hydrate (SCH) and 5% menthol were tested. Swelling index, ex vivo residence time, mucoadhesion strength, in vivo testing of mucoadhesion time, in vitro dissolution and ex vivo permeation were carried out. Furthermore, compatibility and accelerated stability studies were performed for the drug excipients. Finally, drug bioavailability of the BH.2HCl-optimized buccal mucoadhesive formulation was compared with that of the orally administered Betaserc® 24 mg tablet in six healthy male volunteers. Results Formulation F10, which contained a combination of 35% guar gum and 5% sodium carboxymethyl cellulose, exhibited long adhesion time, high adhesion strength and diminished irritation to volunteers and showed zero-order release kinetics. SCH produced a significant enhancement in permeation of BH.2HCl across buccal mucosa. BH.2HCl-optimized buccal mucoadhesive formulation showed percentage relative bioavailability of 177%. Conclusion The developed mucoadhesive tablets represent a promising alternative for the buccal delivery of BH.2HCl. PMID:28008227

Formulation studies on ibuprofen sodium-cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola

2016-01-01

The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid-solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.

Long-term adherence and effects on grip strength and upper leg performance of prescribed supplemental vitamin D in pregnant and recently pregnant women of Somali and Swedish birth with 25-hydroxyvitamin D deficiency: a before-and-after treatment study.

PubMed

Kalliokoski, Paul; Rodhe, Nils; Bergqvist, Yngve; Löfvander, Monica

2016-11-15

Muscular weakness and severe vitamin D deficiency is prevalent in Somali (veiled) pregnant women, Sweden. The study aims here were to explore adherence to prescribed supplemental vitamin D in new mothers with vitamin D deficiency and its effects on grip strength and upper leg performance in Somali (target group TG) and Swedish women (reference group RG) from spring through winter. A before- and after study was designed. A cross-sectional sample of women in antenatal care with serum 25-OHD ≤50 nmol/L were prescribed one or two tablets daily (800 or 1600 IU vitamin D3 with calcium) for 10 months. Reminders were made by Somali nurses (TG) or Swedish doctors (RG). Baseline and 10 month measurements of plasma nmol/L 25-OHD, maximal grip strength held for 10 s (Newton, N) and ability to squat (yes;no) were done. Total tablet intake (n) was calculated. Outcome variables were changes from baseline in grip strength and ability to squat. Predicting variables for change in grip strength and ability to squat were calculated using linear and binary regression in final models. Undetectable 25-OHD values (<10 nmol/L) were replaced with '9' in statistic calculations. Seventy-one women (46 TG, 1/3 with undetectable baseline 25-OHD; 25 RG) participated. At the 10-month follow up, 17% TG and 8% RG women reported having refrained from supplement. Mean 25-OHD increased 16 to 49 nmol/L (TG) and 39 nmol/L to 67 nmol/L (RG), (both p < 0.001). Grip strength had improved from 153 to 188 N (TG) (p < 0.001) and from 257 to 297 N (RG) (p = 0.003) and inability to squat had decreased in TG (35 to 9, p < 0.001). Intake of number of tablets predicted increased grip strength (B 0.067, 95%CI 0.008-0.127, p = 0.027). One tablet daily (>300 in total) predicted improved ability to squat (OR 16; 95% CI 1.8-144.6). Adherence to supplemental vitamin D and calcium should be encouraged as an even moderate intake was associated to improved grip strength and upper leg performance, which was particularly useful for the women with severe 25-OHD deficiency and poor physical performance at baseline. ClinicalTrials.gov Identifier: NCT02922803 . Date of registration: September 28, 2016.

7 CFR 58.339 - Containers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... suitable container constructed of stainless steel or other equally non-corrosive material. The liners shall... strengthened or changed as frequently as necessary to keep the solution full strength and in good condition. (2... should be stacked only as high as the firmness of the product will support weight, so as not to crush or...

7 CFR 58.339 - Containers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... suitable container constructed of stainless steel or other equally non-corrosive material. The liners shall... strengthened or changed as frequently as necessary to keep the solution full strength and in good condition. (2... should be stacked only as high as the firmness of the product will support weight, so as not to crush or...

7 CFR 58.339 - Containers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... suitable container constructed of stainless steel or other equally non-corrosive material. The liners shall... strengthened or changed as frequently as necessary to keep the solution full strength and in good condition. (2... should be stacked only as high as the firmness of the product will support weight, so as not to crush or...

7 CFR 58.339 - Containers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... suitable container constructed of stainless steel or other equally non-corrosive material. The liners shall... strengthened or changed as frequently as necessary to keep the solution full strength and in good condition. (2... should be stacked only as high as the firmness of the product will support weight, so as not to crush or...

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations.

PubMed

Mitra, Biplob; Wolfe, Chad; Wu, Sy-Juen

2018-05-01

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60 °C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25 °C/60% RH and 40 °C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.

Effect of crumb rubber on the mechanical properties of crushed recycled pavement materials.

PubMed

Li, Jie; Saberian, Mohammad; Nguyen, Bao Thach

2018-07-15

The low-carbon footprint of using recycled construction and demolition (C&D) aggregates in civil engineering infrastructure applications has been considered to be a significant solution for the replacement of conventional pavement aggregates. Investigations regarding the use of crumb rubber in the base and subbase layers of pavement have been well documented. However, information on the effects of crumb rubber and its size within C&D aggregates as the base/subbase layers is still very limited. In this study, crumb rubber with particle sizes ranging from 400 to 600 μm (fine) to 10-15 mm (coarse), 20 mm recycled crushed concrete (RCC), and 20 mm crushed rock (CR) were used. The crumb rubber was added to the two groups of C&D aggregates at 0.5, 1 and 2% by weight percentages of the aggregates. The effect of crumb rubber on the mechanical properties (such as California bearing ratio, unconfined compressive strength, aggregate crushing value, dynamic lightweight cone penetrometer, Clegg impact value, Los Angeles abrasion values, and resilient modulus) of the C&D aggregates was then examined. Based on the experimental test results, it was found that crumb rubber can be recycled as a waste material for the base and subbase layers in the pavement. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design of a novel bilayered gastric mucoadhesive system for localized and unidirectional release of lamotrigine

PubMed Central

Mohana Raghava Srivalli, K.; Lakshmi, P.K.; Balasubramaniam, J.

2012-01-01

Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 23 full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 103 dyn/cm2 was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t90% at 6th and 12th hours, respectively. The “n” value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength. PMID:24109205

Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree.

PubMed

Hayashi, Yoshihiro; Oishi, Takuya; Shirotori, Kaede; Marumo, Yuki; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

2018-07-01

The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes. First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10 kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation. Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors. This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.

The effect of various sintering temperature on used refractory towards its physical properties

NASA Astrophysics Data System (ADS)

Sudibyo; Wulandari, Y. R.; Amin, M.; Azhar

2018-01-01

The used magnesia refractory from the kiln of cement industry was successfully recycled to new refractory using Kaolin as an adhesive. In this work, the temperatures of sintering were varied from 1000°C to 1500°C. The result shows that the increment temperature effects in sintering process will enhance refractory physical properties such as bulk density, cold crushing strength or pressure strength and thermal conductivity. Meanwhile, the porosity was decreased as the increase of the sintering temperature.

Preparation and in vitro/in vivo characterization of porous sublingual tablets containing ternary kneaded solid system of vinpocetine with î-cyclodextrin and hydroxy Acid.

PubMed

Aburahma, Mona H; El-Laithy, Hanan M; Hamza, Yassin El-Said

2010-01-01

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetineâs poor aqueous solubility by preparing kneaded solid systems of the drug with Î-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tabletsâ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with Î-Cyclodextrin and tartaric acid could be useful for therapeutic application.

Preparation and characterization of bioactive glass tablets and evaluation of bioactivity and cytotoxicity in vitro.

PubMed

Chen, Jianhui; Zeng, Lei; Chen, Xiaofeng; Liao, Tianshun; Zheng, Jiafu

2018-09-01

In this study, the SiO 2 -CaO-P 2 O 5 ternary component of bioactive glass particles were successfully synthesized by sol-gel method, then the bioactive glass particles were pressed into tablets with dry pressing molding technology. The physicochemical structure, in-vitro bioactivity and biocompatibility of BG tablets were characterized by various methods, such as XRD、SEM、FTIR, etc. The results showed that the sol-gel bioactive glass particle was distinguished with its amorphous structure and micron-size. After being soaked in Tris-Hcl solution for 15 d, the bioactive glass tablets didn't collapse. Also, the mineralization assay in vitro showed that the bioactive glass tablets had good capability of inducing the formation of hydroxycarbonate apatite (HCA) after being immersed in simulated body fluid (SBF). In addition, the cytotoxicity assay indicated that the osteoblast (MC3T3) grew well on the surface of bioactive glass tablets. According to the above results, the bioactive glass tablets presented good mechanical strength, excellent apatite-forming activity and high biocompatibility, which demonstrated their potential applications in the field of bone defect repairing.

How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Comparison of four magnesium carbonates.

PubMed

Freitag, Franziska; Kleinebudde, Peter

2003-07-01

The effect of roll compaction/dry granulation on the particle and bulk material characteristics of different magnesium carbonates was evaluated. The flowability of all materials could be improved, even by the application of low specific compaction forces. The tablet properties made of powder and dry granulated magnesium carbonate were compared. Roll compaction/dry granulation resulted in a modified compactibility of the material and, consequently, tablets with reduced tensile strength. The higher relative tap density of the compacted material does not allow a densification to the same extent as the uncompacted powder. The degree of densification during tableting can be expressed as the ratio of the relative tablet density to the relative tap density of the feed material. Increasing the specific compaction forces resulted in higher apparent mean yield pressure, gained from Heckel plots, of all materials analysed. The partial loss of compactibility leads to the demand of low loads during roll compaction. Comparing the tablet properties of different magnesium carbonates reveals an obvious capping disposition. However, it depends on the type of magnesium carbonate, the specific compaction force and also on the tableting force applied.

Pharmacokinetics of fixed-dose combinations of empagliflozin/metformin compared with individual tablets in healthy subjects.

PubMed

Rojas, Christina; Link, Jasmin; Meinicke, Thomas; Macha, Sreeraj

2016-04-01

To compare the pharmacokinetics of fixed-dose combination (FDC) tablets of empagliflozin/metformin with individual tablets taken together. In 3 randomized, open-label studies, healthy subjects received a single FDC tablet of empagliflozin/metformin in 1 of 6 dose combinations (empagliflozin 12.5 mg or 5 mg; metformin 500 mg, 850 mg, or 1,000 mg) in 1 period and the individual tablets taken together under fed conditions in another period. Empagliflozin 12.5 mg/metformin 1,000 mg FDC and individual tablets were also given under fasted conditions. Adjusted geometric mean ratios (GMRs) of empagliflozin area under the plasma concentration-time curve (AUC(0-∞)) for the FDCs vs. individual tablets ranged from 97.92 to 106.00%, and 90% CIs ranged from 93.53 to 109.39%. Adjusted GMRs of empagliflozin maximum plasma concentrations (C(max)) for the FDCs vs. individual tablets ranged from 100.97 to 106.52%, and 90% CIs ranged from 95.86 to 118.35%. Adjusted GMRs of metformin AUC(0-∞) for the FDCs vs. individual tablets ranged from 96.25 to 101.61%, and 90% CIs ranged from 88.54 to 106.62%. Adjusted GMRs of metformin C(max) for the FDCs vs. individual tablets ranged from 93.83 to 102.95%, and 90% CIs ranged from 88.01 to 109.08%. Bioequivalence was also established under fasted conditions for empagliflozin 12.5 mg/metformin 1,000 mg FDC vs. individual tablets taken together. All treatments were well tolerated. Empagliflozin/metformin FDC tablets were found to be bioequivalent to individual tablets taken together at all tested dose strengths.

Production of extended release mini-tablets using directly compressible grades of HPMC.

PubMed

Mohamed, Faiezah A A; Roberts, Matthew; Seton, Linda; Ford, James L; Levina, Marina; Rajabi-Siahboomi, Ali R

2013-11-01

Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company. To compare the properties of HPMC DC (METHOCEL™ K4M and K100M) with regular (REG) HPMC grades. Particle size distribution and flowability of HPMC REG and DC were evaluated. 3 mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2-4 kN and speeds of 5, 10, 15 or 20 rpm. Mini-tablets containing HPMC REG were produced manually. The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79-4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles. Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.

Chewability testing in the development of a chewable tablet for hyperphosphatemia.

PubMed

Lanz, Michael; Baldischweiler, Jan; Kriwet, Burkhard; Schill, Jutta; Stafford, John; Imanidis, Georgios

2014-12-01

The official Pharmacopeia does not include a test procedure for the in vitro estimation of the chewability of tablets and publications in the scientific literature on this subject are rare. The purpose of this study was to evaluate a number of different test procedures for assessing chewability, starting from standard breaking force and strength testing and progressing to develop new procedures that simulate the actual chewing action on tablets. A further goal was to apply these test procedures to characterize the chewability of the novel phosphate binder PA21 in comparison with a commercially available phosphate binder chewable tablet product based on lanthanum (Fosrenol®) and a chewable tablet product containing calcium (Calcimagon®) - the latter being used as a standard for its very good chewability. For this purpose, a number of development formulations (different batches of PA21) were tested. The radial or diametrical tablet breaking force offers a poor means of assessing chewability while the axial breaking force was concluded to better reflect the effect of chewing on the tablet. Measurement of tablet behavior upon repeated loading afforded the best simulation of the actual chewing action and was found to have a good discriminating power with respect to chewability of the tested tablets, especially when the tablet was moistened with artificial saliva. The developed tests are shown to be more suitable for evaluating chewing properties of tablets than currently used Pharmacopeial tests. Following ICHQ6, which calls for specification of hardness for chewable tablets, these test procedures enabled the optimal chewability features of PA21 tablets in development to be confirmed whilst still maintaining capabilities for robust production and transportation processes.

Oral drug therapy in elderly with dysphagia: between a rock and a hard place!

PubMed Central

Logrippo, Serena; Ricci, Giovanna; Sestili, Matteo; Cespi, Marco; Ferrara, Letizia; Palmieri, Giovanni F; Ganzetti, Roberta; Bonacucina, Giulia; Blasi, Paolo

2017-01-01

Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient’s informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed. PMID:28203065

Eudragit E as excipient for production of granules and tablets from Phyllanthus niruri L spray-dried extract.

PubMed

Pereira de Souza, Tatiane; Martínez-Pacheco, Ramón; Gómez-Amoza, José Luiz; Petrovick, Pedro Ros

2007-04-27

The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract from Phyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2 x 3 factorial design, where Eudragit E concentration and compression force were the independent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formulations in order to achieve less water sorption and improve the release of the extract from the tablets.

Relationship between Age and the Ability to Break Scored Tablets

PubMed Central

Notenboom, Kim; Vromans, Herman; Schipper, Maarten; Leufkens, Hubert G. M.; Bouvy, Marcel L.

2016-01-01

Background: Practical problems with the use of medicines, such as difficulties with breaking tablets, are an often overlooked cause for non-adherence. Tablets frequently break in uneven parts and loss of product can occur due to crumbling and powdering. Health characteristics, such as the presence of peripheral neuropathy, decreased grip strength and manual dexterity, can affect a patient's ability to break tablets. As these impairments are associated with aging and age-related diseases, such as Parkinson's disease and arthritis, difficulties with breaking tablets could be more prevalent among older adults. The objective of this study was to investigate the relationship between age and the ability to break scored tablets. Methods: A comparative study design was chosen. Thirty-six older adults and 36 young adults were systematically observed with breaking scored tablets. Twelve different tablets were included. All participants were asked to break each tablet by three techniques: in between the fingers with the use of nails, in between the fingers without the use of nails and pushing the tablet downward with one finger on a solid surface. It was established whether a tablet was broken or not, and if broken, whether the tablet was broken accurately or not. Results: The older adults experienced more difficulties to break tablets compared to the young adults. On average, the older persons broke 38.1% of the tablets, of which 71.0% was broken accurately. The young adults broke 78.2% of the tablets, of which 77.4% was broken accurately. Further analysis by mixed effects logistic regression revealed that age was associated with the ability to break tablets, but not with the accuracy of breaking. Conclusions: Breaking scored tablets by hand is less successful in an elderly population compared to a group of young adults. Health care providers should be aware that tablet breaking is not appropriate for all patients and for all drugs. In case tablet breaking is unavoidable, a patient's ability to break tablets should be assessed by health care providers and instructions on the appropriate method of breaking should be provided. PMID:27507946

Tablet compression tooling - Impact of punch face edge modification.

PubMed

Anbalagan, Parthiban; Heng, Paul Wan Sia; Liew, Celine Valeria

2017-05-30

The influence of punch face edge geometry modification on tablet compression and the properties of the resultant tablets produced on a rotary press were investigated. The results revealed that tablets produced from the punches with radius edge face geometry consistently displayed better physical quality; higher tensile strength and lower capping tendency. Modification of the angled edge of the bevel face to the curved edge of the radius face, enabled deeper punch penetration in the die cavity during the compression cycle, bringing about greater compact densification. Improved die fill packing increased interparticulate bond formation and helped to dissipate destructive elasticity within the compact, consequently reduced tablet expansion during the decompression phase. The positive impact of punch face edge modification was also more noticeable at a higher turret speed. The application of the precompression force along with dwell time extension amplified the tableting performance of radius edge punch face design to a greater extent when compared to bevel edge punch face design. This could be attributed to the enhanced packing efficiency at both precompression and main compression stages. Copyright © 2017 Elsevier B.V. All rights reserved.

To Study Capping or Lamination Tendency of Tablets Through Evaluation of Powder Rheological Properties and Tablet Mechanical Properties of Directly Compressible Blends.

PubMed

Dudhat, Siddhi M; Kettler, Charles N; Dave, Rutesh H

2017-05-01

Air entrapment efficiency of the powders is one of the main factors leading to occurrence of capping or lamination tendency of tablets manufactured from the directly compressible powder blends. The purpose of the current research was to study this underlying cause leading to occurrence of capping or lamination of tablets through evaluation of powder rheological properties. Powder blends were prepared by addition of 0% w/w to 100% w/w of individual active pharmaceutical ingredient (API) [two model API: acetaminophen (APAP) and ibuprofen (IBU)] with microcrystalline cellulose without and with 0.5% w/w Magnesium Stearate as lubricant. Powder rheological properties were analyzed using FT4 Powder Rheometer for dynamic, bulk, and shear properties. Tablet mechanical properties of the respective blends were studied by determining the ability of the material to form tablet of specific strength under applied compaction pressure through tabletability profile. The results showed that powder rheometer distinguished the powder blends based on their ability to relieve entrapped air along with the distinctive flow characteristics. Powder blend prepared with increasing addition of APAP displayed low powder permeability as compared to IBU blends with better powder permeability, compressibility and flow characteristics. Also, lubrication of the APAP blends did not ease their ability to relieve air. Tabletability profiles revealed the potential occurrence of capping or lamination in tablets prepared from the powder blends with high APAP content. This study can help scientist to understand tableting performance at the early-developmental stages and can avoid occurrence capping and lamination of tablets.

Nano/micro/meso scale interactions in mechanics of pharmaceutical solid dosage forms

NASA Astrophysics Data System (ADS)

Akseli, Ilgaz

Oral administration in form tablets has been the most common method for delivering drug to the human systemic blood circulation accurately and reproducibly due to its established manufacturing methods and reliability as well as cost. The mechanical criteria for a successful powder-to-tablet processing are good flowability, compressibility and compactibility that are closely related to the mechanical and adhesion properties of the particles and particle strength. In this thesis, air-coupled acoustic and ultrasonic techniques are presented and demonstrated as noncontact and nondestructive methods for physical (mechanical) integrity monitoring and mechanical characterization of tablets. A testing and characterization experimental platform for defect detection, coating thickness and mechanical property determination of tablets was also developed. The presented air-coupled technique was based on the analysis of the transient vibrational responses of a tablet in both temporal and spectral domains. The contact ultrasonic technique was based on the analysis of the propagation speed of an acoustic pulse launched into a tablet and its reflection from the coat-core interface of the tablet. In defect monitoring, the ultimate objective is to separate defective tablets from nominal ones. In the case of characterization, to extract the coating layer thicknesses and mechanical properties of the tablets from a subset of the measured resonance frequencies, an iterative computational procedure was demonstrated. In the compaction monitoring experiments, an instrumented punch and a cylindrical die were employed to extract the elasticity properties of tablets during compaction. To study the effect of compaction kinetics on tablet properties and defect, finite element analyses of single layer and bilayer tablets were performed. A noncontact work-of-adhesion technique was also demonstrated to determine the work-of-adhesion of pharmaceutical powder particles.

49 CFR 238.405 - Longitudinal static compressive strength.

Code of Federal Regulations, 2010 CFR

2010-10-01

... volumes of a power car or a trailer car designed to crush as part of the crash energy management design... deformation to the cab, unless equivalent protection to crewmembers is provided under an alternate design approach, validated through analysis and testing, and approved by FRA under the provisions of § 238.21. (b...

49 CFR 238.405 - Longitudinal static compressive strength.

Code of Federal Regulations, 2011 CFR

2011-10-01

... volumes of a power car or a trailer car designed to crush as part of the crash energy management design... deformation to the cab, unless equivalent protection to crewmembers is provided under an alternate design approach, validated through analysis and testing, and approved by FRA under the provisions of § 238.21. (b...

Preparation and characterization of ibuprofen-cetyl alcohol beads by melt solidification technique: effect of variables.

PubMed

Maheshwari, Manish; Ketkar, Anant R; Chauhan, Bhaskar; Patil, Vinay B; Paradkar, Anant R

2003-08-11

Ibuprofen (IBU) exhibits short half-life, poor compressibility, flowability and caking tendency. IBU melt has sufficiently low viscosity and exhibits interfacial tension sufficient to form droplet even at low temperature. A single step novel melt solidification technique (MST) was developed to produce IBU beads with lower amounts of excipient. Effect of variables was studied using a 3(2) factorial approach with speed of agitation and amount of cetyl alcohol (CA) as variables. The beads were evaluated using DSC, FT-IR and scanning electron microscope (SEM). Yield, micromeritic properties, crushing strength and release kinetics were also studied. Spherical beads with a method yield of above 90% were obtained. The data was analyzed by response surface methodology. The variables showed curvilinear relationship with yield in desired particle size range, crushing strength and, bulk and tap density. The drug release followed non-Fickian case II transport and the release rate decreased linearly with respect to amount of CA in the initial stages followed by curvilinearity at later stages of elution. The effect of changing porosity and tortuosity was well correlated.

The use of index tests to determine the mechanical properties of crushed aggregates from Precambrian basement complex rocks, Ado-Ekiti, SW Nigeria

NASA Astrophysics Data System (ADS)

Afolagboye, Lekan Olatayo; Talabi, Abel Ojo; Oyelami, Charles Adebayo

2017-05-01

This study assessed the possibility of using index tests to determine the mechanical properties of crushed aggregates. The aggregates used in this study were derived from major Precambrian basement rocks in Ado-Ekiti, Nigeria. Regression analyses were performed to determine the empirical relations that mechanical properties of the aggregates may have with the point load strength (IS(50)), Schmidt rebound hammer value (SHR) and unconfined compressive strength (UCS) of the rocks. For all the data, strong correlation coefficients were found between IS(50), SHR, UCS, and mechanical properties of the aggregates. The regression analysis conducted on the different rocks separately showed that correlations coefficients obtained between the IS(50), SHR, UCS and mechanical properties of the aggregates were stronger than those of the grouped rocks. The T-test and F-test showed that the derived models were valid. This study has shown that the mechanical properties of the aggregates can be estimated from IS(50), SHR and USC but the influence of rock type on the relationships should be taken into consideration.

Relationship between mechanical-property and energy-absorption trends for composite tubes

NASA Technical Reports Server (NTRS)

Farley, Gary L.

1992-01-01

U.S. Army helicopters are designed to dissipate prescribed levels of crash impact kinetic energy without compromising the integrity of the fuselage. Because of the complexity of the energy-absorption process it is imperative for designers of energy-absorbing structures to develop an in-depth understanding of how and why composite structures absorb energy. A description of the crushing modes and mechanisms of energy absorption for composite tubes and beams is presented. Three primary crushing modes of composite structures including transverse shearing, lamina bending, and local buckling are described. The experimental data presented show that fiber and matrix mechanical properties and laminate stiffness and strength mechanical properties cannot reliably predict the energy-absorption response of composite tubes.

Simultaneous determination of the impurity and radial tensile strength of reduced glutathione tablets by a high selective NIR-PLS method.

PubMed

Li, Juan; Jiang, Yue; Fan, Qi; Chen, Yang; Wu, Ruanqi

2014-05-05

This paper establishes a high-throughput and high selective method to determine the impurity named oxidized glutathione (GSSG) and radial tensile strength (RTS) of reduced glutathione (GSH) tablets based on near infrared (NIR) spectroscopy and partial least squares (PLS). In order to build and evaluate the calibration models, the NIR diffuse reflectance spectra (DRS) and transmittance spectra (TS) for 330 GSH tablets were accurately measured by using the optimized parameter values. For analyzing GSSG or RTS of GSH tablets, the NIR-DRS or NIR-TS were selected, subdivided reasonably into calibration and prediction sets, and processed appropriately with chemometric techniques. After selecting spectral sub-ranges and neglecting spectrum outliers, the PLS calibration models were built and the factor numbers were optimized. Then, the PLS models were evaluated by the root mean square errors of calibration (RMSEC), cross-validation (RMSECV) and prediction (RMSEP), and by the correlation coefficients of calibration (R(c)) and prediction (R(p)). The results indicate that the proposed models have good performances. It is thus clear that the NIR-PLS can simultaneously, selectively, nondestructively and rapidly analyze the GSSG and RTS of GSH tablets, although the contents of GSSG impurity were quite low while those of GSH active pharmaceutical ingredient (API) quite high. This strategy can be an important complement to the common NIR methods used in the on-line analysis of API in pharmaceutical preparations. And this work expands the NIR applications in the high-throughput and extraordinarily selective analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Experimental study on compressive strength of sediment brick masonry

NASA Astrophysics Data System (ADS)

Woen, Ean Lee; Malek, Marlinda Abdul; Mohammed, Bashar S.; Chao-Wei, Tang; Tamunif, Muhammad Thaqif

2018-02-01

The effects of pre-wetted unit bricks, mortar type and slenderness ratio of prisms on the compressive strength and failure mode of newly developed sediment brick have been evaluated and compared to clay brick and cement-sand bricks. The results show that pre-wetted sediment brick masonry exhibits higher compressive strength of up to 20% compared to the dry sediment masonry. Using cement-lime mortar leads to lower compressive strength compared to cement mortar. However, the sediment brick masonry with the cement lime mortar exhibit higher compressive strength in comparison with cement mortar masonry. More of diagonal shear cracks have been observed in the failure mode of the sediment bricks masonry compared to clay and cement-sand bricks masonry that show mostly vertical cracks and crushing. The sediment unit bricks display compressive strength in between clay and cement-sand bricks.

Correlation between loose density and compactibility of granules prepared by various granulation methods.

PubMed

Murakami, H; Yoneyama, T; Nakajima, K; Kobayashi, M

2001-03-23

The objectives of this study were to prepare the lactose granules by various granulation methods using polyethylene glycol 6000 (PEG 6000) as a binder and to evaluate the effects of granulation methods on the compressibility and compactibility of granules in tabletting. Lactose was granulated by seven granulation methods -- four wet granulations including wet massing granulation, wet high-speed mixer granulation, wet fluidized bed granulation and wet tumbling fluidized bed granulation; and three melt granulations including melt high-speed mixer granulation, melt fluidized bed granulation and melt tumbling fluidized bed granulation. The loose density, angle of repose, granule size distribution, mean diameter of granules, and the tensile strength and porosity of tablets were evaluated. The compactibilities of granules were varied by the granulation methods. However, the difference in compactibility of granules could not be explained due to the difference in compressibility, since there was no difference in Heckel plots due to granulation methods. Among their granule properties, the loose density of granules seemed to have a correlation with the tablet strength regardless of the granulation methods.

Stable Isotope Profiling of Internet-Sourced Viagra® and 'generic- Viagra' Tablets

NASA Astrophysics Data System (ADS)

Kemp, Helen; Meier-Augenstein, Wolfram

2013-04-01

Viagra® manufactured by Pfizer was the first prescription drug for the treatment of erectile dysfunction (ED), a condition that is estimated to affect 1 in 10 men at some stage in their lives (1). Viagra® contains the active pharmaceutical ingredient (API) sildenafil, as the citrate salt. Sildenafil, along with Tadalafil and Vardenafil belong to a class of drugs known as phosphodiesterase type 5 (PDE5) inhibitors. Since its first production in 1998, Viagra® has generated well in excess of 10 billion US dollars in sales (2) and with Pfizers' patent extended to April 2020 (3) it still remains the only sildenafil-based treatment option for sufferers of ED in the US. There are no legal 'generic-Viagra' formulations available in the US. However, formulations containing sildenafil citrate as API are widely available over the internet and often sold as 'generic Viagra'. These cheaper alternatives are often manufactured under less than ideal conditions with little or no QA/QC procedures in place. The World Health Organisation recognised the scale of the problem in its 2010 bulletin "Growing threat from counterfeit medicines" (4) and quotes a Dutch study cited in the International Journal of Clinical Practice in which from a cohort of 370 seized Viagra® samples, only 10 were genuine. We sourced a variety of tablets sold for the treatment of ED which claimed to have sildenafil citrate as API. Viagra®, 'generic-Viagra', Kamagra, Silagra and Filagra tablets were ordered via the internet and supplied from both UK-based pharmacies as well as overseas suppliers (Hong Kong, India, Vanuata). In this small-scale pilot study, we present results from bulk 2H/18O and 13C/15N stable isotope analysis performed on crushed tablets from 23 samples of internet-sourced tablets sold for the treatment of ED and purported to contain sildenafil citrate as API. References 1. www.healthcare.org.uk 2. www.moneynews.com 3. US Patent & trademark office (www.uspto.gov) 4. WHO bulletin 2010; 88:247-248

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test.

PubMed

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-10-01

To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm(2). The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window.

Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets.

PubMed

Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Yang, Chan; Cui, Xianglong; Shi, Xinyuan; Qiao, Yanjiang

2016-01-01

The quality of Chinese herbal medicine tablets suffers from batch-to-batch variability due to a lack of manufacturing process understanding. In this paper, the Panax notoginseng saponins (PNS) immediate release tablet was taken as the research subject. By defining the dissolution of five active pharmaceutical ingredients and the tablet tensile strength as critical quality attributes (CQAs), influences of both the manipulated process parameters introduced by an orthogonal experiment design and the intermediate granules' properties on the CQAs were fully investigated by different chemometric methods, such as the partial least squares, the orthogonal projection to latent structures, and the multiblock partial least squares (MBPLS). By analyzing the loadings plots and variable importance in the projection indexes, the granule particle sizes and the minimal punch tip separation distance in tableting were identified as critical process parameters. Additionally, the MBPLS model suggested that the lubrication time in the final blending was also important in predicting tablet quality attributes. From the calculated block importance in the projection indexes, the tableting unit was confirmed to be the critical process unit of the manufacturing line. The results demonstrated that the combinatorial use of different multivariate modeling methods could help in understanding the complex process relationships as a whole. The output of this study can then be used to define a control strategy to improve the quality of the PNS immediate release tablet.

The effect of roof strength on reducing occupant injury in rollovers.

PubMed

Herbst, Brian; Forrest, Steve; Orton, Tia; Meyer, Steven E; Sances, Anthony; Kumaresan, Srirangam

2005-01-01

Roof crush occurs and potentially contributes to serious or fatal occupant injury in 26% of rollovers. It is likely that glazing retention is related to the degree of roof crush experienced in rollover accidents. Occupant ejection (including partial ejection) is the leading cause of death and injury in rollover accidents. In fatal passenger car accidents involving ejection, 34% were ejected through the side windows. Side window glass retention during a rollover is likely to significantly reduce occupant ejections. The inverted drop test methodology is a test procedure to evaluate the structural integrity of roofs under loadings similar to those seen in real world rollovers. Recent testing on many different vehicle types indicates that damage consistent with field rollover accidents can be achieved through inverted drop testing at very small drop heights. Drop test comparisons were performed on 16 pairs of vehicles representing a large spectrum of vehicle types. Each vehicle pair includes a production vehicle and a vehicle with a reinforced roof structure dropped under the same test conditions. This paper offers several examples of post-production reinforcements to roof structures that significantly increase the crush resistance of the roof as measured by inverted drop tests. These modifications were implemented with minimal impact on vehicle styling, interior space and visual clearances. The results of these modifications indicate that roof crush can be mitigated by nearly an order of magnitude, as roof crush was reduced by 44-91% with only a 1-2.3% increase in vehicle weight. Additionally, this paper analyzes the glazing breakage patterns in the moveable tempered side windows on the side adjacent to the vehicle impact point in the inverted drop tests. A comparison is made between the production vehicles and the reinforced vehicles in order to determine if the amount roof crush is related to glazing integrity in the side windows. Lastly, two drop test pairs, performed with Hybrid III test dummies, indicates that the reduction of roof crush resulted in a direct reduction in neck loading and therefore an increase in occupant protection.

Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

PubMed

Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

2012-05-30

The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of moisture content, temperature and exposure time on the physical stability of chitosan powder and tablets.

PubMed

Viljoen, Joe M; Steenekamp, Jan H; Marais, Andries F; Kotzé, Awie F

2014-06-01

Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations. Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration. The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time. Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon® VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature. The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions. It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets. It was evident that the presence of Kollidon® VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets. The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions. It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25 °C as well as at a relatively low humidity (<60%) to prevent deterioration of physical properties. Direct compression of chitosan granules which contained 5%w/w Kollidon® VA64 produced the best formulation in terms of physical stability at the different conditions.

Signal intensity of lanthanum carbonate on magnetic resonance images: phantom study.

PubMed

Nakamura, Shinichi; Awai, Kazuo; Komi, Masanori; Morita, Kosuke; Namimoto, Tomohiro; Yanaga, Yumi; Utsunomiya, Daisuke; Date, Shuji; Yamashita, Yasuyuki

2011-06-01

Lanthanum carbonate (LC) is used to treat hyperphosphatemia. The purpose of this study was to investigate the signal intensity (SI) of LC on magnetic resonance imaging (MRI) scans of phantoms. LC tablets were thoroughly ground and mixed with distilled water or edible agar (0.05, 0.25, 0.5, and 2.5 mg/ml) in plastic bottles. Four intact tablets were placed in plastic bottles that did or did not contain distilled water or agar. Two radiologists consensually evaluated T1- and T2-weighted images (WIs) obtained with 1.5- and 3.0-T MRI systems for the SI of unground and ground tablets. On T1- and T2WI, the SIs of the LC suspensions and the solvents alone were similar; the SIs of unground tablets alone and of the air were also similar. Unground tablets in phantoms filled with solvent exhibited lower SI than the solvent. Ground tablets in suspension were not visualized on MRI or computed tomography. These results remained unchanged regardless of differences in magnetic field strength or the solvent used. Ground LC had no contrast enhancement effect on T1WI; on T2WI it did not affect the SI of the solvent. Unground LC tablets may be visualized as a "filling defect" on MRI.

Preparation and In Vitro/In Vivo Characterization of Porous Sublingual Tablets Containing Ternary Kneaded Solid System of Vinpocetine with β-Cyclodextrin and Hydroxy Acid

PubMed Central

Aburahma, Mona H.; El-Laithy, Hanan M.; Hamza, Yassin El-Said

2010-01-01

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetine’s poor aqueous solubility by preparing kneaded solid systems of the drug with β-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tablets’ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with β-Cyclodextrin and tartaric acid could be useful for therapeutic application. PMID:21179352

Co-spray Drying with HPMC as a Platform to Improve Direct Compaction Properties of Various Tablet Fillers.

PubMed

Li, JinZhi; Zhao, LiJie; Lin, Xiao; Shen, Lan; Feng, Yi

2017-11-01

Many commonly used tablet fillers are not suitable for direct compaction process due to insufficient properties, mainly of flowability and compactability. This work therefore aimed to use co-spray drying with HPMC as a platform to improve direct compaction properties of various tablet fillers. Starch, calcium hydrogen phosphate dihydrate (DCPD), and mannitol were chosen as a representative of three types of commonly used fillers (i.e. organic macromolecules, water-insoluble inorganic salts, and water-soluble small molecular carbohydrates), respectively. The five-level central composite design-response surface methodology was used (i) to investigate the effects of HPMC level and solid content of the feed on various powder, tableting, and tablet properties of composite excipients, and (ii) to optimize the composition. The results showed that the impacts of the two factors on various properties of composite excipients showed great similarity, despite of significantly different primary properties of the parent fillers, and the HPMC level was the main contributor to the majority of the impacts. An increase in HPMC level significantly improved tablet tensile strength and various tableting parameters. For all the three fillers, their optimized composite excipients provided by the established models showed excellent performances as predicted. The platform suggested is confirmed to be effective and promising.

Release mechanism of doxazosin from carrageenan matrix tablets: Effect of ionic strength and addition of sodium dodecyl sulphate.

PubMed

Kos, Petra; Pavli, Matej; Baumgartner, Saša; Kogej, Ksenija

2017-08-30

The polyelectrolyte matrix tablets loaded with an oppositely charged drug exhibit complex drug-release mechanisms. In this study, the release mechanism of a cationic drug doxazosin mesylate (DM) from matrix tablets based on an anionic polyelectrolyte λ-carrageenan (λ-CARR) is investigated. The drug release rates from λ-CARR matrices are correlated with binding results based on potentiometric measurements using the DM ion-sensitive membrane electrode and with molecular characteristics of the DM-λ-CARR-complex particles through hydrodynamic size measurements. Experiments are performed in solutions with different ionic strength and with the addition of an anionic surfactant sodium dodecyl sulphate (SDS). It is demonstrated that in addition to swelling and erosion of tablets, the release rates depend strongly on cooperative interactions between DM and λ-CARR. Addition of SDS at concentrations below its critical micelle concentration (CMC) slows down the DM release through hydrophobic binding of SDS to the DM-λ-CARR complex. On the contrary, at concentrations above the CMC SDS pulls DM from the complex by forming mixed micelles with it and thus accelerates the release. Results involving SDS show that the concentration of surfactants that are naturally present in gastrointestinal environment may have a great impact on the drug release process. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental and Modeling Studies of Crush, Puncture, and Perforation Scenarios in the Steven Impact Test

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vandersall, K S; Chidester, S K; Forbes, J W

2002-06-28

The Steven test and associated modeling has greatly increased the fundamental knowledge of practical predictions of impact safety hazards for confined and unconfined explosive charges. Building on a database of initial work, experimental and modeling studies of crush, puncture, and perforation scenarios were investigated using the Steven impact test. The descriptions of crush, puncture, and perforation arose from safety scenarios represented by projectile designs that ''crush'' the energetic material or either ''puncture'' with a pinpoint nose or ''perforate'' the front cover with a transportation hook. As desired, these scenarios offer different aspects of the known mechanisms that control ignition: friction,more » shear and strain. Studies of aged and previously damaged HMX-based high explosives included the use of embedded carbon foil and carbon resistor gauges, high-speed cameras, and blast wave gauges to determine the pressure histories, time required for an explosive reaction, and the relative violence of those reactions, respectively. Various ignition processes were modeled as the initial reaction rate expression in the Ignition and Growth reaction rate equations. Good agreement with measured threshold velocities, pressure histories, and times to reaction was calculated for LX-04 impacted by several projectile geometries using a compression dependent ignition term and an elastic-plastic model with a reasonable yield strength for impact strain rates.« less

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

PubMed

Agrawal, Anjali; Dudhedia, Mayur; Deng, Weibin; Shepard, Kevin; Zhong, Li; Povilaitis, Edward; Zimny, Ewa

2016-02-01

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

PubMed

Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

2013-08-01

The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

Composition and process for making an insulating refractory material

DOEpatents

Pearson, A.; Swansiger, T.G.

1998-04-28

A composition and process are disclosed for making an insulating refractory material. The composition includes calcined alumina powder, flash activated alumina powder, an organic polymeric binder and a liquid vehicle which is preferably water. Starch or modified starch may also be added. A preferred insulating refractory material made with the composition has a density of about 2.4--2.6 g/cm{sup 3} with reduced thermal conductivity, compared with tabular alumina. Of importance, the formulation has good abrasion resistance and crush strength during intermediate processing (commercial sintering) to attain full strength and refractoriness.

In vitro and in vivo evaluation of medicinal carbon granules and tablet on the adsorption of acetaminophen.

PubMed

Yamamoto, Kenta; Onishi, Hiraku; Ito, Akihiko; Machida, Yoshiharu

2007-01-10

Medicinal carbon (MC) granules were prepared by wet granulation using maltitol (MT), and the MC tablet was produced by compression of the granules. The physical properties and the in vitro adsorption capacity for AA of the formulations were examined. Further, the effects of MC alone and the granules on gastrointestinal absorption of AA were examined in rats when they were administered intragastrically at 15 or 45 min after the intragastrical administration of AA. AA was rapidly adsorbed by MC, and the maximum adsorption capacity of MC was 0.329g AA per gram MC. The granules and tablet exhibited adequate strength, and the tablet disintegrated rapidly. The granules and tablet showed similar adsorption profiles, but somewhat lower adsorption capacity than MC alone. MC alone and granules administered at 15 min reduced the AUC(0-infinity) significantly against the control (no treatment); however, the suppression effect on the plasma concentration was lower with the granules than with MC alone. Thus, granules and tablet are useful as a compact dosage form of MC; though the reduced adsorption capacity must be taken into account in order to expect efficacy equivalent to that of MC alone.

Influence of rate of force application during compression on tablet capping.

PubMed

Sarkar, Srimanta; Ooi, Shing Ming; Liew, Celine Valeria; Heng, Paul Wan Sia

2015-04-01

Root cause and possible processing remediation of tablet capping were investigated using a specially designed tablet press with an air compensator installed above the precompression roll to limit compression force and allow extended dwell time in the precompression event. Using acetaminophen-starch (77.9:22.1) as a model formulation, tablets were prepared by various combinations of precompression and main compression forces, set precompression thickness, and turret speed. The rate of force application (RFA) was the main factor contributing to the tablet mechanical strength and capping. When target force above the force required for strong interparticulate bond formation, the resultant high RFA contributed to more pronounced air entrapment, uneven force distribution, and consequently, stratified densification in compact together with high viscoelastic recovery. These factors collectively had contributed to the tablet capping. As extended dwell time assisted particle rearrangement and air escape, a denser and more homogenous packing in the die could be achieved. This occurred during the extended dwell time when a low precompression force was applied, followed by application of main compression force for strong interparticulate bond formation that was the most beneficial option to solve capping problem. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

PubMed

Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A

2017-02-25

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug. Copyright © 2016 Elsevier B.V. All rights reserved.

49 CFR 238.405 - Longitudinal static compressive strength.

Code of Federal Regulations, 2012 CFR

2012-10-01

... crash refuge for crewmembers occupying the cab of a power car, the underframe of the cab of a power car... volumes of a power car or a trailer car designed to crush as part of the crash energy management design...) The underframe of the occupied volume of each trailer car shall resist a minimum longitudinal static...

49 CFR 238.405 - Longitudinal static compressive strength.

Code of Federal Regulations, 2014 CFR

2014-10-01

... crash refuge for crewmembers occupying the cab of a power car, the underframe of the cab of a power car... volumes of a power car or a trailer car designed to crush as part of the crash energy management design...) The underframe of the occupied volume of each trailer car shall resist a minimum longitudinal static...

49 CFR 238.405 - Longitudinal static compressive strength.

Code of Federal Regulations, 2013 CFR

2013-10-01

... crash refuge for crewmembers occupying the cab of a power car, the underframe of the cab of a power car... volumes of a power car or a trailer car designed to crush as part of the crash energy management design...) The underframe of the occupied volume of each trailer car shall resist a minimum longitudinal static...

Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression.

PubMed

Avgerinos, Theodoros; Kantiranis, Nikolaos; Panagopoulou, Athanasia; Malamataris, Stavros; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

2018-02-01

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit ® RSPO the matrix former and citric acid or Lutrol ® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (P e ) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters. Resistance to extrusion and tablet ejection force were reduced by Lutrol ® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P e correlated with T and resistance to deformation of the corresponding pellets (r 2  = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r 2  = 0.990) and for HME the diffusion coefficient (D e ) and retreat rate constant (k b ) decreased linearly with T (r 2  = 0.934 and 0.972). Lutrol ® F127 and citric acid are efficient plasticizers and Lutrol ® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

Evaluation of a rotary tablet press simulator as a tool for the characterization of compaction properties of pharmaceutical products.

PubMed

Michaut, F; Busignies, V; Fouquereau, C; de Barochez, B Huet; Leclerc, B; Tchoreloff, P

2010-06-01

The Stylcam 100R, a rotary press simulator, was designed to simulate speed profiles of rotary tablet presses. Such a simulator was qualified by numerous laboratories and, actually, its ability to be used for studying the behaviour of powders under pressure should be examined. Then, the purpose of this work was to investigate the performances of the Stylcam 100R for characterizing the compaction behaviour and the tabletting properties of pharmaceutical powders. The compressibility of three pharmaceutical excipients (microcrystalline cellulose, dicalcium phosphate dihydrate and alpha-lactose monohydrate) was studied. Four compression speeds were used on the compaction simulator. Force-displacement cycles were associated with two energy parameters, the specific total energy (Es(tot)) and the specific expansion energy (Es(exp)). The mean yield pressure was calculated from Heckel's plots obtained with the in-die method. The diametral tensile strength of compacts was measured in order to evaluate mechanical properties. To evaluate the accuracy of all these parameters, a comparative study was carried out on an eccentric instrumented press. The values of energy parameters and tensile strengths of tablets are close between the eccentric press and the compaction simulator, whatever the compression speed on the latter. The mean yield pressure values obtained using the two presses are different. Finally, the Stylcam 100R seems to be a good tool for characterising tabletting properties of powders, except for the Heckel's model probably due to an unadapted equation of deformation and a lack of accuracy of the displacement transducers. Future improvements should allow correcting these two points. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Higher Strength Lanthanum Carbonate Provides Serum Phosphorus Control With a Low Tablet Burden and Is Preferred by Patients and Physicians: A Multicenter Study

PubMed Central

Mehrotra, Rajnish; Martin, Kevin J.; Fishbane, Steven; Sprague, Stuart M.; Zeig, Steven; Anger, Michael

2008-01-01

Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with ≤3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages ≤3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. PMID:18579668

Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties.

PubMed

Monteyne, Tinne; Vancoillie, Jochem; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

2016-10-01

The pharmaceutical industry has a growing interest in alternative manufacturing models allowing automation and continuous production in order to improve process efficiency and reduce costs. Implementing a switch from batch to continuous processing requires fundamental process understanding and the implementation of quality-by-design (QbD) principles. The aim of this study was to examine the relationship between formulation-parameters (type binder, binder concentration, drug-binder miscibility), process-parameters (screw speed, powder feed rate and granulation temperature), granule properties (size, size distribution, shape, friability, true density, flowability) and tablet properties (tensile strength, friability, dissolution rate) of four different drug-binder formulations using Design of experiments (DOE). Two binders (polyethylene glycol (PEG) and Soluplus®) with a different solid state, semi-crystalline vs amorphous respectively, were combined with two model-drugs, metoprolol tartrate (MPT) and caffeine anhydrous (CAF), both having a contrasting miscibility with the binders. This research revealed that the granule properties of miscible drug-binder systems depended on the powder feed rate and barrel filling degree of the granulator whereas the granule properties of immiscible systems were mainly influenced by binder concentration. Using an amorphous binder, the tablet tensile strength depended on the granule size. In contrast, granule friability was more important for tablet quality using a brittle binder. However, this was not the case for caffeine-containing blends, since these phenomena were dominated by the enhanced compression properties of caffeine Form I, which was formed during granulation. Hence, it is important to gain knowledge about formulation behavior during processing since this influences the effect of process parameters onto the granule and tablet properties. Copyright © 2016 Elsevier B.V. All rights reserved.

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

PubMed

Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

2016-10-01

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

Experimental and numerical characterization of expanded glass granules

NASA Astrophysics Data System (ADS)

Chaudry, Mohsin Ali; Woitzik, Christian; Düster, Alexander; Wriggers, Peter

2018-07-01

In this paper, the material response of expanded glass granules at different scales and under different boundary conditions is investigated. At grain scale, single particle tests can be used to determine properties like Young's modulus or crushing strength. With experiments like triaxial and oedometer tests, it is possible to examine the bulk mechanical behaviour of the granular material. Our experimental investigation is complemented by a numerical simulation where the discrete element method is used to compute the mechanical behaviour of such materials. In order to improve the simulation quality, effects such as rolling resistance, inelastic behaviour, damage, and crushing are also included in the discrete element method. Furthermore, the variation of the material properties of granules is modelled by a statistical distribution and included in our numerical simulation.

Latent structure analysis in the pharmaceutical process of tablets prepared by wet granulation.

PubMed

Uehara, Naoto; Hayashi, Yoshihiro; Mochida, Hiroshi; Otoguro, Saori; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2016-01-01

Granule characteristics are some of the important intermediate qualities that determine tablet properties. However, the relationships between granule and tablet characteristics are poorly understood. The aim of this study was to elucidate relationships among formulation factors, granule characteristics, and tablet properties using a non-linear response surface method (RSM) incorporating a thin-plate spline interpolation (RSM-S) and a Bayesian network (BN). Tablets containing lactose (Lac), cornstarch (CS), and microcrystalline cellulose (MCC) were prepared by wet granulation. Ten formulations were prepared by an extreme vertices design. The angle of repose (Y 1 ), compressibility (Y 2 ), cohesion force (Y 3 ), internal friction angle (Y 4 ), and mean particle size (Y 5 ) were measured as granule characteristics. Tensile strength (TS) and disintegration time (DT) were measured as tablet properties. RSM-S results showed that TS increased with increasing amounts of MCC and Lac. DT decreased with increasing amounts of MCC and CS. The optimal BN models were predicted using four evaluation indices -Y 3 was shown to be the most important factor for TS, whereas Y 2 , Y 3 , and Y 4 were relatively important for predicting DT. Moreover, tablets with excellent tablet properties (i.e. high TS and low DT) were produced by relatively high Y 1 , low Y 2 , high Y 3 , high Y 4 , and middle Y 5 values, and resulted from the middle of MCC, middle-to-low CS, low Lac, and middle-to-low magnesium stearate (Mg-St) amounts. The RSM-S and BN techniques are useful for revealing complex relationships among formulation factors, granule characteristics, and tablet properties.

Effect of particle size on in-die and out-of-die compaction behavior of ranitidine hydrochloride polymorphs.

PubMed

Khomane, Kailas S; Bansal, Arvind K

2013-09-01

The present study investigates the effect of particle size on compaction behavior of forms I and II of ranitidine hydrochloride. Compaction studies were performed using three particle size ranges [450-600 (A), 300-400 (B), and 150-180 (C) μm] of both the forms, using a fully instrumented rotary tableting machine. Compaction data were analyzed for out-of-die compressibility, tabletability, and compactibility profiles and in-die Heckel and Kawakita analysis. Tabletability of the studied size fractions followed the order; IB > IA > > IIC > IIB > IIA at all the compaction pressures. In both the polymorphs, decrease in particle size improved the tabletability. Form I showed greater tabletability over form II at a given compaction pressure and sized fraction. Compressibility plot and Heckel and Kawakita analysis revealed greater compressibility and deformation behavior of form II over form I at a given compaction pressure and sized fraction. Decrease in particle size increased the compressibility and plastic deformation of both the forms. For a given polymorph, improved tabletability of smaller sized particles was attributed to their increased compressibility. However, IA and IB, despite poor compressibility and deformation, showed increased tabletability over IIA, IIB, and IIC by virtue of their greater compactibility. Microtensile testing also revealed higher nominal fracture strength of form I particles over form II, thus, supporting greater compactibility of form I. Taken as a whole, though particle size exhibited a trend on tabletability of individual forms, better compactibility of form I over form II has an overwhelming impact on tabletability.

Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets

PubMed Central

Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Yang, Chan; Cui, Xianglong; Shi, Xinyuan; Qiao, Yanjiang

2016-01-01

The quality of Chinese herbal medicine tablets suffers from batch-to-batch variability due to a lack of manufacturing process understanding. In this paper, the Panax notoginseng saponins (PNS) immediate release tablet was taken as the research subject. By defining the dissolution of five active pharmaceutical ingredients and the tablet tensile strength as critical quality attributes (CQAs), influences of both the manipulated process parameters introduced by an orthogonal experiment design and the intermediate granules’ properties on the CQAs were fully investigated by different chemometric methods, such as the partial least squares, the orthogonal projection to latent structures, and the multiblock partial least squares (MBPLS). By analyzing the loadings plots and variable importance in the projection indexes, the granule particle sizes and the minimal punch tip separation distance in tableting were identified as critical process parameters. Additionally, the MBPLS model suggested that the lubrication time in the final blending was also important in predicting tablet quality attributes. From the calculated block importance in the projection indexes, the tableting unit was confirmed to be the critical process unit of the manufacturing line. The results demonstrated that the combinatorial use of different multivariate modeling methods could help in understanding the complex process relationships as a whole. The output of this study can then be used to define a control strategy to improve the quality of the PNS immediate release tablet. PMID:27932865

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test

PubMed Central

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-01-01

Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm2. The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window. PMID:21927013

Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions.

PubMed

Dohi, Masafumi; Momose, Wataru; Yoshino, Hiroyuki; Hara, Yuko; Yamashita, Kazunari; Hakomori, Tadashi; Sato, Shusaku; Terada, Katsuhide

2016-02-05

Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in-process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test. Copyright © 2015 Elsevier B.V. All rights reserved.

Continuous manufacturing of delta mannitol by cospray drying with PVP.

PubMed

Vanhoorne, V; Van Bockstal, P-J; Van Snick, B; Peeters, E; Monteyne, T; Gomes, P; De Beer, T; Remon, J P; Vervaet, C

2016-03-30

Mannitol is a frequently used diluent in the production of tablets due to its non-hygroscopic character and low drug interaction potential. Although the δ-polymorph of mannitol has superior tabletability in comparison to α- and β-mannitol, the latter are most commonly used because large-scale production of δ-mannitol is difficult. Therefore, a continuous method for production of δ-mannitol was developed in the current study. Spray drying an aqueous solution of mannitol and PVP in a ratio of 4:1 resulted in formation of δ-mannitol. The tabletability of a physical mixture of spray dried δ-mannitol with PVP (5%) and paracetamol (75%) was clearly superior to the tabletability of physical mixtures consisting of spray dried α- and β-mannitol with PVP (5%) and paracetamol (75%) which confirmed the excellent tableting properties of the δ-polymorph. In addition, a coprocessing method was applied to coat paracetamol crystals with δ-mannitol and PVP. The tabletability of the resulting coprocessed particles consisting of 5% PVP, 20% δ-mannitol and 75% paracetamol reached a maximal tensile strength of 2.1 MPa at a main compression pressure of 260 MPa. Moreover the friability of tablets compressed at 184 MPa was only 0.5%. This was attributed to the excellent compression properties of δ-mannitol and the coating of paracetamol crystals with δ-mannitol and PVP during coprocessing. Copyright © 2016 Elsevier B.V. All rights reserved.

Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

PubMed

Hayashi, Yoshihiro; Oshima, Etsuko; Maeda, Jin; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2012-01-01

A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Q(β)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(β) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics.

Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

PubMed Central

2012-01-01

Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to <25 kg, with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria. Patients were randomized (2:1) to pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid suspension) for three days. Results Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P < .0001). Pyronaridine-artesunate was non-inferior to artemether-lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). The incidence of drug-related adverse events was 37.2% (132/355) with pyronaridine-artesunate, 44.4% (80/180) with artemether-lumefantrine. Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups. From day 3 until study completion, one patient in each treatment group had peak alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. Trial registration ClinicalTrials.gov: identifier NCT00541385 PMID:23113947

Design and Optimization of Domperidone Fast Dissolving Tablet Using Central Composite Design.

PubMed

Shailendra, Bhatt; Shailendra, Mandge; Manish, Jaimini; Singh, Tanwar Yuveraj; Priti, Trivedi

2015-01-01

The main aim present work was to optimize fast dissolving tablet (FDT) formulation using response surface approach. The variables studied were sodium bicarbonate (X1), citric acid (X2), and superdisintegrant, Ac-Di-Sol (X3). The main aspect of present work was to develop FDT of Domperidone which possesses fast disintegration and high mechanical strength. It was found that the response was affected by all the three factors studied. The statistical models were successfully used to prepare FDT of Domperidone with fast disintegration (31.08 seconds) and adequate hardness (4.1 kg/cm(2)). Pharmacokinetic studies in rats showed statistically insignificant difference (p>0.05) between Domperidone fast dissolving tablet (DFDT) and market product. This concluded that optimized FDT is bioequivalent with the marketed formulation. The values of Tmax were found to be 0.5 h and 0.75 h for DFDT and reference product, respectively. Conditioned place aversion study was performed on Swiss Albino mice and the study showed the better anti emetic potency of optimized FDT in nauseated condition over market product (p<0.05). Thus, the present investigation conclusively demonstrates the potential role in terms of rapid disintegration and high mechanical strength.

Evaluation of disintegrants functionality for orodispersible mini tablets.

PubMed

Soulairol, Ian; Chaheen, Mohammad; Tarlier, Nicolas; Aubert, Adrien; Bataille, Bernard; Sharkawi, Tahmer

2017-11-01

This work evaluates the functionalities of different superdisintegrants (SD) for manufacturing orodispersible mini tablets (ODMT) by direct compression. Twenty-three formulations varying in SD type, concentration, and lubricant were used to manufacture ODMT. The ODMT were then characterized for the following properties: friability, porosity, tensile strength, in vivo and in vitro disintegration time (DT). The results show that the presence, type, and concentration of SD did not influence friability, porosity, or tablet tensile strength. With regards to in vivo DT, only cross-linked poly (vinyl pyrrolidone) improved DT in all the tested formulations. Results also showed that when using microcrystalline cellulose (MCC) above 20% in the formulation, DT is longer. Cross-linked carboxymethyl cellulose accelerates DT when the MCC content is less than 20%. As for cross-linked carboxymethyl starch and calcium alginate showed no improvement on DT. Results for in vitro DT were all shorter than in vivo results and there was no correlation with the in vivo evaluation. This study shows that there is a need to develop better in vitro testing that precisely simulates in vivo conditions and that are adapted to ODMT. This standardization of the test methods for ODMTs must be accompanied by an improvement in the comprehension of SD mechanisms.

Stability of medicines after repackaging into multicompartment compliance aids: eight criteria for detection of visual alteration.

PubMed

Albert, Valerie; Lanz, Michael; Imanidis, Georgios; Hersberger, Kurt E; Arnet, Isabelle

2017-01-01

Multicompartment compliance aids (MCA) are widely used by patients. They support the management of medication and reduce unintentional nonadherence. MCA are filled with medicines unpacked from their original packaging. Swiss pharmacists currently provide MCA for 1-2 weeks, although little and controversial information exists on the stability of repackaged medicines. We aimed to validate the usefulness of a simple screening method capable of detecting visual stability problems with repackaged medicines. We selected eight criteria for solid formulations from The International Pharmacopoeia : (1) rough surface, (2) chipping, (3) cracking, (4) capping, (5) mottling, (6) discoloration, (7) swelling, and (8) crushing. A selection of 24 critical medicines was repackaged in three different MCA (Pharmis ® , SureMed™, and self-produced blister) and stored at room temperature for 4 weeks. Pharmis ® was additionally stored at accelerated conditions. Appearance was scored weekly. Six alterations (rough surface, cracking, mottling, discoloration, swelling, and crushing) were observed at accelerated conditions. No alteration was observed at room temperature, except for the chipping of tablets that had been stuck to cold seal glue. The eight criteria can detect alterations of the appearance of oral solid medicines repackaged in MCA. In the absence of specific guidelines, they can serve as a simple screening method in community pharmacies for identifying medicines unsuitable for repackaging.

A systematic and mechanistic evaluation of aspartic acid as filler for directly compressed tablets containing trimethoprim and trimethoprim aspartate.

PubMed

ElShaer, Amr; Hanson, Peter; Mohammed, Afzal R

2013-04-01

The generally accepted paradigm of 'inert' and 'mono functional' excipient in dosage form has been recently challenged with the development of individual excipients capable of exhibiting multiple functions (e.g. binder-disintegrants, surfactant which affect P-gp function). The proposed study has been designed within the realm of multifunctionality and is the first and novel investigation towards evaluation of aspartic acid as a filler and disintegration enhancing agent for the delivery of biopharmaceutical class IV model drug trimethoprim. The study investigated powder characteristics using angle of repose, laser diffractometry and scanning electron microscopy (SEM). The prepared tablets were characterised using Heckel analysis, disintegration time and tensile strength measurements. Although Heckel analysis revealed that both TMP and TMP aspartate salt have high elasticity, the salt form produced a stronger compact which was attributed to the formation of agglomerates. Aspartic acid was found to have high plasticity, but its incorporation into the formulations was found to have a negative impact on the compaction properties of TMP and its salt. Surface morphology investigations showed that mechanical interlocking plays a vital role in binding TMP crystals together during compaction, while the small particle size of TMP aspartate agglomerates was found to have significant impact on the tensile strength of the tablets. The study concluded that aspartic acid can be employed as filler and disintegrant and that compactability within tablets was independent of the surface charge of the excipients. Copyright © 2012 Elsevier B.V. All rights reserved.

The exploded hand syndrome: a report of five industrial injury cases.

PubMed

Al-Qattan, M M

2013-10-01

The term 'exploded hand syndrome' refers to a specific type of crush injury to the hand in which a high compressive force excessively flattens the hand leading to thenar muscle extrusion through burst lacerations. Out of 89 crushed hands seen over a period of seven years, only five had exploded hand syndrome. They were all male industrial workers ranging in age between 24 and 55 years. All patients had thenar muscle extrusion. Other concurrent injuries included fractures/dislocations, compartment syndrome, and ischaemia. All patients were treated by excision of the extruded intrinsic muscles, as well as primary management of concurrent injuries. All patients had functional assessment including: motor power and sensory testing, range of motion of hand joints, and the quick DASH score. Objective testing showed reduced sensibility in the thumb, reduced grip strength (mean 52% of contralateral hand), reduced pinch strength (mean of 27% of contralateral hand), reduced thumb opposition (the mean Kapandji Score was 5 out of 10), and deficits in the range of motion of the metacarpophalangeal and interphalangeal joints of the thumb. The quick DASH score ranged from 11 to 49 and only two patients were able to go back to regular manual work.

Toucan and hornbill beaks: a comparative study.

PubMed

Seki, Yasuaki; Bodde, Sara G; Meyers, Marc A

2010-02-01

The structure and mechanical behavior of Toco Toucan (Ramphastos toco) and Wreathed Hornbill (Rhyticeros undulatus) beaks were compared. The beak of both species is a sandwich-structured composite, having an exterior, or rhamphotheca, consisting of multiple layers of keratin scales and a core composed of a fibrous network of bony closed-cell foam. The rhamphotheca is an arrangement of approximately 50microm diameter, overlapping, keratin tiles. The hornbill rhamphotheca exhibits a surface morphology on the ridged casque that is distinguishable from that observed on the bill proper. Intermediate filaments in the keratin matrix were observed by transmission electron microscopy. The Young's modulus measurements of toucan rhamphotheca indicate isotropy in longitudinal and transverse directions, whereas those of hornbill rhamphotheca may suggest anisotropy. The compressive response of beak foam is governed by brittle crushing behavior. The crushing strength of hornbill foam is six times higher than that of toucan foam. Micro- and nanoindentation hardness values were measured for rhamphotheca and foam trabeculae of toucan and hornbill specimens. The sandwich design of beaks was analyzed using the Karam-Gibson and Dawson-Gibson models. The presence of a cellular core increases the bending resistance (Brazier moment) by a factor of 3-6 while decreasing the compressive strength by only 50%.

Stability of allopurinol and of five antineoplastics in suspension.

PubMed

Dressman, J B; Poust, R I

1983-04-01

The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.

Gradual Ordering in Red Abalone Nacre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbert, P. U. P. A.; Metzler, Rebecca A.; Zhou, Dong

2008-09-03

Red abalone (Haliotis rufescens) nacre is a layered composite biomineral that contains crystalline aragonite tablets confined by organic layers. Nacre is intensely studied because its biologically controlled microarchitecture gives rise to remarkable strength and toughness, but the mechanisms leading to its formation are not well understood. Here we present synchrotron spectromicroscopy experiments revealing that stacks of aragonite tablet crystals in nacre are misoriented with respect to each other. Quantitative measurements of crystal orientation, tablet size, and tablet stacking direction show that orientational ordering occurs not abruptly but gradually over a distance of 50 {micro}m. Several lines of evidence indicate thatmore » different crystal orientations imply different tablet growth rates during nacre formation. A theoretical model based on kinetic and gradual selection of the fastest growth rates produces results in qualitative and quantitative agreement with the experimental data and therefore demonstrates that ordering in nacre is a result of crystal growth kinetics and competition either in addition or to the exclusion of templation by acidic proteins as previously assumed. As in other natural evolving kinetic systems, selection of the fastest-growing stacks of tablets occurs gradually in space and time. These results suggest that the self-ordering of the mineral phase, which may occur completely independently of biological or organic-molecule control, is fundamental in nacre formation.« less

Evaluation of co-processed excipients used for direct compression of orally disintegrating tablets (ODT) using novel disintegration apparatus.

PubMed

Brniak, Witold; Jachowicz, Renata; Krupa, Anna; Skorka, Tomasz; Niwinski, Krzysztof

2013-01-01

The compendial method of evaluation of orodispersible tablets (ODT) is the same disintegration test as for conventional tablets. Since it does not reflect the disintegration process in the oral cavity, alternative methods are proposed that are more related to in vivo conditions, e.g. modified dissolution paddle apparatus, texture analyzer, rotating shaft apparatus, CCD camera application, or wetting time and water absorption ratio measurement. In this study, three different co-processed excipients for direct compression of orally disintegrating tablets were compared (Ludiflash, Pharmaburst, F-Melt). The properties of the prepared tablets such as tensile strength, friability, wetting time and water absorption ratio were evaluated. Disintegration time was measured using the pharmacopoeial method and the novel apparatus constructed by the authors. The apparatus was based on the idea of Narazaki et al., however it has been modified. Magnetic resonance imaging (MRI) was applied for the analysis of the disintegration mechanism of prepared tablets. The research has shown the significant effect of excipients, compression force, temperature, volume and kind of medium on the disintegration process. The novel apparatus features better correlation of disintegration time with in vivo results (R(2) = 0.9999) than the compendial method (R(2) = 0.5788), and presents additional information on the disintegration process, e.g. swelling properties.

Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

PubMed Central

Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

2015-01-01

The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

Strength Restoration of Cracked Sandstone and Coal under a Uniaxial Compression Test and Correlated Damage Source Location Based on Acoustic Emissions.

PubMed

Feng, Xiaowei; Zhang, Nong; Zheng, Xigui; Pan, Dongjiang

2015-01-01

Underground rock masses have shown a general trend of natural balance over billions of years of ground movement. Nonetheless, man-made underground constructions disturb this balance and cause rock stability failure. Fractured rock masses are frequently encountered in underground constructions, and this study aims to restore the strength of rock masses that have experienced considerable fracturing under uniaxial compression. Coal and sandstone from a deep-buried coal mine were chosen as experimental subjects; they were crushed by uniaxial compression and then carefully restored by a chemical adhesive called MEYCO 364 with an innovative self-made device. Finally, the restored specimens were crushed once again by uniaxial compression. Axial stress, axial strain, circumferential strain, and volumetric strain data for the entire process were fully captured and are discussed here. An acoustic emission (AE) testing system was adopted to cooperate with the uniaxial compression system to provide better definitions for crack closure thresholds, crack initiation thresholds, crack damage thresholds, and three-dimensional damage source locations in intact and restored specimens. Several remarkable findings were obtained. The restoration effects of coal are considerably better than those of sandstone because the strength recovery coefficient of the former is 1.20, whereas that of the latter is 0.33, which indicates that MEYCO 364 is particularly valid for fractured rocks whose initial intact peak stress is less than that of MEYCO 364. Secondary cracked traces of restored sandstone almost follow the cracked traces of the initial intact sandstone, and the final failure is mainly caused by decoupling between the adhesive and the rock mass. However, cracked traces of restored coal only partially follow the traces of intact coal, with the final failure of the restored coal being caused by both bonding interface decoupling and self-breakage in coal. Three-dimensional damage source locations manifest such that AE events are highly correlated with a strength recovery coefficient; the AE events show a decreasing tendency when the coefficient is larger than 1, and vice versa. This study provides a feasible scheme for the reinforcement of fractured rock masses in underground constructions and reveals an internal mechanism of the crushing process for restored rock masses, which has certain instructive significance.

Strength Restoration of Cracked Sandstone and Coal under a Uniaxial Compression Test and Correlated Damage Source Location Based on Acoustic Emissions

PubMed Central

Feng, Xiaowei; Zhang, Nong; Zheng, Xigui; Pan, Dongjiang

2015-01-01

Underground rock masses have shown a general trend of natural balance over billions of years of ground movement. Nonetheless, man-made underground constructions disturb this balance and cause rock stability failure. Fractured rock masses are frequently encountered in underground constructions, and this study aims to restore the strength of rock masses that have experienced considerable fracturing under uniaxial compression. Coal and sandstone from a deep-buried coal mine were chosen as experimental subjects; they were crushed by uniaxial compression and then carefully restored by a chemical adhesive called MEYCO 364 with an innovative self-made device. Finally, the restored specimens were crushed once again by uniaxial compression. Axial stress, axial strain, circumferential strain, and volumetric strain data for the entire process were fully captured and are discussed here. An acoustic emission (AE) testing system was adopted to cooperate with the uniaxial compression system to provide better definitions for crack closure thresholds, crack initiation thresholds, crack damage thresholds, and three-dimensional damage source locations in intact and restored specimens. Several remarkable findings were obtained. The restoration effects of coal are considerably better than those of sandstone because the strength recovery coefficient of the former is 1.20, whereas that of the latter is 0.33, which indicates that MEYCO 364 is particularly valid for fractured rocks whose initial intact peak stress is less than that of MEYCO 364. Secondary cracked traces of restored sandstone almost follow the cracked traces of the initial intact sandstone, and the final failure is mainly caused by decoupling between the adhesive and the rock mass. However, cracked traces of restored coal only partially follow the traces of intact coal, with the final failure of the restored coal being caused by both bonding interface decoupling and self-breakage in coal. Three-dimensional damage source locations manifest such that AE events are highly correlated with a strength recovery coefficient; the AE events show a decreasing tendency when the coefficient is larger than 1, and vice versa. This study provides a feasible scheme for the reinforcement of fractured rock masses in underground constructions and reveals an internal mechanism of the crushing process for restored rock masses, which has certain instructive significance. PMID:26714324

The Acute Effect of Cryotherapy on Muscle Strength and Shoulder Proprioception.

PubMed

Torres, Rui; Silva, Filipa; Pedrosa, Vera; Ferreira, João; Lopes, Alexandre

2017-11-01

Cryotherapy, a common intervention used by clinicians, poses several benefits in managing acute injuries. However, cooling muscle tissue can interfere with muscular properties and the sensory-motor system. The aim of this study was to analyze the influence of cryotherapy with a crushed-ice pack on shoulder proprioception concerning joint position sense, force sense, the threshold for detecting passive movement, and maximal force production. A randomized, double-blind controlled trial. 48 healthy women aged 22.6 ± 0.4 y with a mean body mass index of 22.8 ±0.37 kg/m2 and a percentage of body fat of 15.4 ± 1.5%. In the experimental group, a crushed-ice pack was applied to the shoulder for 15 min, whereas participants in the control group applied a sandbag at skin temperature, also for 15 min. An isokinetic dynamometer was used to assess maximal voluntary contraction, force sense, joint position sense, and the threshold for detecting passive movement. Paired sample t tests revealed that maximal voluntary isometric contraction decreased significantly after cryotherapy (P ≤ .001), or approximately 10% of the reduction found in both muscular groups assessed. Shoulder position sense (P < .001) and the threshold for detecting passive movement (P = .01 and P = .01 for lateral and medial shoulder rotator muscles, respectively) also suffered significant impairment. Nevertheless, no significant differences emerged in force sense at 20% and 50% of maximal force reproduction (P = .41 and P = .10 for lateral rotator muscles at 20% and 50%, respectively; and P = .20 and P = .09 for medial rotator muscles at 20% and 50%, respectively). Applying a crushed-ice pack to the shoulder for 15 min negatively affected muscle strength and impaired shoulder proprioception by decreasing joint position sense and the threshold for detecting passive movement.

Roof-crush strength improvement using rigid polyurethane foam

NASA Astrophysics Data System (ADS)

Lilley, K.; Mani, A.

1998-08-01

Recent bending tests show the effectiveness of rigid, polyurethane foam in improving the strength of automotive body structures. By using foam, it is possible to reduce pillar sections, and to reduce thicknesses or eliminate reinforcements inside the pillars, and thereby offset the mass increase due to the foam filling. Further tests showed that utilizing the foam filling in a B-pillar to reduce section size can save ~20 mm that could be utilized to add energy absorbing structures in order to meet the new interior head impact requirements specified by the federal motor vehicle safety standards (FMVSS) 201 Head Impact Protection upgrade.

A Pilot Stability Study of Dehydroepiandrosterone Rapid-dissolving Tablets Prepared by Extemporaneous Compounding.

PubMed

Rush, Steven D; Vernak, Charlene; Zhao, Fang

2017-01-01

Dehydroepiandrosterone supplementation is used to treat a variety of conditions. Rapid-dissolving tablets are a relatively novel choice for compounded dehydroepiandrosterone dosage forms. While rapid-dissolving tablets offer ease of administration, there are uncertainties about the physical and chemical stability of the drug and dosage form during preparation and over long-term storage. This study was designed to evaluate the stability of dehydroepiandrosterone rapid-dissolving tablets just after preparation and over six months of storage. The Professional Compounding Centers of America rapid-dissolving tablet mold and base formula were used to prepare 10-mg strength dehydroepiandrosterone rapid-dissolving tablets. The formulation was heated at 100°C to 110°C for 30 minutes, released from the mold, and cooled at room temperature for 30 minutes. The resulting rapid-dissolving tablets were individually packaged in amber blister packs and stored in a stability chamber maintained at 25°C and 60% relative humidity. The stability samples were pulled at pre-determined time points for evaluation, which included visual inspection, tablet weight check, United States Pharmacopeia disintegration test, and stability-indicating high-performance liquid chromatography. The freshly prepared dehydroepiandrosterone rapiddissolving tablets exhibited satisfactory chemical and physical stability. Time 0 samples disintegrated within 40 seconds in water kept at 37°C. The high-performance liquid chromatographic results confirmed that the initial potency was 101.9% of label claim and that there was no chemical degradation from the heating procedure. Over six months of storage, there were no significant changes in visual appearance, physical integrity, or disintegration time for any of the stability samples. The high-performance liquid chromatographic results also indicated that dehydroepiandrosterone rapid-dissolving tablets retained >95% label claim with no detectable degradation products. The dehydroepiandrosterone rapid-dissolving tablets investigated in this pilot study were physically and chemically stable during preparation and over six months of storage at 25°C and 60% relative humidity. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

[Application of quality by design in granulation process for ginkgo leaf tablet (Ⅱ)： identification of critical quality attributes].

PubMed

Xu, Bing; Cui, Xiang-Long; Yang, Chan; Wang, Xin; Shi, Xin-Yuan; Qiao, Yan-Jiang

2017-03-01

Quality by design (QbD) highlights the concept of "begin with the end", which means to thoroughly understand the target product quality first, and then guide pharmaceutical process development and quality control throughout the whole manufacturing process. In this paper, the Ginkgo biloba granules intermediates were taken as the research object, and the requirements of the tensile strength of tablets were treated as the goals to establish the methods for identification of granules' critical quality attributes (CQAs) and establishment of CQAs' limits. Firstly, the orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties of 29 batches of granules and the tensile strength of ginkgo leaf tablets, and thereby the potential critical quality attributes (pCQAs) were screened by variable importance in the projection (VIP) indexes. Then, a series of OPLS models were rebuilt by reducing pCQAs variables one by one in view of the rule of VIP values from low to high in sequence. The model performance results demonstrated that calibration and predictive performance of the model had no decreasing trend after variables reduction. In consideration of the results from variables selection as well as the collinearity test and testability of the pCQAs, the median particle size (D₅₀) and the bulk density (Da) were identified as critical quality attributes (CQAs). The design space of CQAs was developed based on a multiple linear regression model established between the CQAs (D₅₀ and Da) and the tensile strength. The control constraints of the CQAs were determined as 170 μm< D₅₀<500 μm and 0.30 g•cm⁻³

Doxycycline concentration over time after storage in a compounded veterinary preparation.

PubMed

Papich, Mark G; Davidson, Gigi S; Fortier, Lisa A

2013-06-15

To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and stored for 28 days. Evaluation study. Doxycycline hyclate tablets (100 mg) crushed and mixed with a 50:50 mixture of syrup and suspension vehicles for oral administration to produce 3 batches each of 2 doxycycline formulations: 33.3 and 166.7 mg/mL. Formulations were stored, protected from light, at room temperature (22° to 26°C [71.6° to 78.8°F]) and at a controlled cold temperature (refrigerated 2° to 8°C [35.6° to 46.4°F]). Doxycycline was extracted from the formulations, and concentration was measured by high-pressure liquid chromatography on days 0 (date of preparation), 1, 4, 7, 14, 21, and 28. Concentrations were compared with those of a US Pharmacopeial Convention reference standard. Formulation quality at each point was also assessed through color change, formulation consistency, and suspension uniformity. On days 0, 1, 4, and 7, the concentration of each formulation was within 90% to 110% of the reference standard (range, 93% to 109%), which was deemed acceptable. However, doxycycline concentrations had decreased dramatically by day 14 and remained low for the duration of the study period. Doxycycline concentrations on days 14, 21, and 28 were all < 20% (range, 14% to 18%) of the reference standard, and the quality of the formulations decreased as well. No effect of storage temperatures on doxycycline concentration was identified. The concentration of doxycycline, compounded from commercial tablets in the vehicles evaluated to yield doses of 33.3 and 166.7 mg/mL, cannot be assured beyond 7 days.

Psychological and Physiological Processes in Figure-Tracing Abilities Measured Using a Tablet Computer: A Study with 7 and 9 Years Old Children

PubMed Central

Giammarco, Enrico; Di Sano, Sergio; Aureli, Tiziana; Cerratti, Paola; Fanò-Illic, Giorgio; Pietrangelo, Tiziana

2016-01-01

The present study investigated the use of a tablet computer to assess figure-tracing skills and their relationships with psychological (visual–perceptual processes, cognitive processes, handwriting skills) and physiological (body mass index, isometric strength of arms) parameters with school-children of second (7–8-year-olds) and fourth (9–10-year-olds) grades. We were also interested in gender differences. The task required tracing of geometric figures on a template, shown on a tablet screen in light gray, for the segments that make up the target figure, one at a time. This figure-tracing tablet test allows acquisition and automated analysis of four parameters: number of strokes (pen lift) for each segment; oscillations of lines drawn with respect to reference lines; pressure of pen on tablet; and average speed of tracing. The results show a trade-off between speed and quality for the tablet parameters, with higher speed associated with more oscillations with respect to the reference lines, and lower number of strokes for each segment, in both male and female children. The involvement of visual–motor integration on the ability to reduce the oscillations in this tablet test was only seen for the male children, while both the male and female children showed a relationship between oscillations and more general/abstract visual–spatial processes. These data confirm the role of visual–motor processes in this figure-tracing tablet test only for male children, while more general visual–spatial processes influence the performance in the tablet test for both sexes. We conclude that the test proposed is useful to screen for grapho-motor difficulties. PMID:27803678

Investigation of an artificial intelligence technology--Model trees. Novel applications for an immediate release tablet formulation database.

PubMed

Shao, Q; Rowe, R C; York, P

2007-06-01

This study has investigated an artificial intelligence technology - model trees - as a modelling tool applied to an immediate release tablet formulation database. The modelling performance was compared with artificial neural networks that have been well established and widely applied in the pharmaceutical product formulation fields. The predictability of generated models was validated on unseen data and judged by correlation coefficient R(2). Output from the model tree analyses produced multivariate linear equations which predicted tablet tensile strength, disintegration time, and drug dissolution profiles of similar quality to neural network models. However, additional and valuable knowledge hidden in the formulation database was extracted from these equations. It is concluded that, as a transparent technology, model trees are useful tools to formulators.

The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices.

PubMed

Asare-Addo, Kofi; Conway, Barbara R; Larhrib, Hassan; Levina, Marina; Rajabi-Siahboomi, Ali R; Tetteh, John; Boateng, Joshua; Nokhodchi, Ali

2013-11-01

The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic strength of the media was varied over a range of 0-0.4M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices. Copyright © 2013 Elsevier B.V. All rights reserved.

Development and evaluation of buccoadhesive tablet for selegiline hydrochloride based on thiolated polycarbophil.

PubMed

Wasnik, Mangesh N; Godse, Rutika D; Nair, Hema A

2014-05-01

Selegiline hydrochloride (SHCl), a monoamine oxidase B inhibitor, is used as an adjunct in the therapy of Parkinson's disease. This study is concerned with the preparation and evaluation of mucoadhesive buccal tablet for controlled systemic delivery of SHCl. Buccal absorption of selegiline can bypass its first-pass metabolism and improve bioavailability accompanied by greatly reduced metabolite formation, which is potentially of enhanced therapeutic value in patients with Parkinson's disease. Polycarbophil-cysteine (PCP-cys) conjugate, which is a thiolated derivative of the mucoadhesive polymer polycarbophil, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-mediated amide bond coupling. Tablets of SHCl based on native and thiolated polycarbophil were prepared. The prepared tablets were evaluated for drug content, swelling behavior, mucoadhesive strength, in vitro drug release, ex vivo permeation and in vitro cytotoxicity. PCP-cys tablets showed enhanced mucoadhesion and retarded drug release compared to polycarbophil tablets. Permeation data of SHCl from matrices prepared using the PCP-cys polymer revealed a significantly higher value of apparent permeability in comparison to polycarbophil, which supported the information in literature that thiolation imparts permeation enhancing properties to mucoadhesive polymers. In vitro cytotoxicity studies on PCP-cys using L-929 mouse fibroblast cell line indicated that conjugation with cysteine does not impart any apparent toxicity to polycarbophil. The results from the study indicate that the buccal delivery of SHCl using thiolated polycarbophil tablet could provide a way for improved therapy of Parkinson's disease.

Triiodothyronine and thyroxine content of desiccated thyroid tablets.

PubMed

Rees-Jones, R W; Larsen, P R

1977-11-01

Triiodothyronine (T3) and thyroxine (T4) were measured by radioimmunoassay in Pronase hydrolysates of four lots each of 1- and 2-grain tablets of desiccated thyroid (Thyroid, Armour) and thyroglobulin (Proloid, Warner-Chilcott). The methodology used was verified by studies of tablets containing known quantities of T4 and T3. One grain of desiccated thyroid contained 12 +/- 1 and 64 +/- 3 microgram (mean +/- SD) of T3 and T4 per tablet, respectively (T4/T3 molar ratio, 4.3). A 1-grain tablet of thyroglobulin contained 16 +/- 2 and 55 +/- 5 microgram of T3 and T4, respectively with a T4/T3 ratio of 2.9. Two-grain tablets generally contained twice the quantity of T3 and T4 in the 1-grain preparations. The variation in T3 and T4 content between the four lots of each tablet strength for each product was 10% or less. These estimates of T3 and T4 content are 1.5- to 2-fold greater than those previously published. This difference probably results from the more sophisticated methodology now available which does not require chromatographic separation of T3 and T4 or iodometry. Using calculations based on published estimates of T4 and T3 absorption and of the T3/T4 potency ratio, it would appear that the T3 content of desiccated thyroid and thyroglobulin provide approximately 39% and 51%, respectively, of the thyromimetic activity of these two medications.

A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes.

PubMed

Kushner, Joseph; Langdon, Beth A; Hicks, Ian; Song, Daniel; Li, Fasheng; Kathiria, Lalji; Kane, Anil; Ranade, Gautam; Agarwal, Kam

2014-02-01

The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity <4% RSD, tablet potency: 94%-105%, content uniformity <6% RSD, acceptance value ≤ 15, solid fraction: 0.82-0.86, tensile strength >1 MPa, friability ≤ 0.2% weight loss, and disintegration time < 4 min. The filler-lubricant particle size ratio exhibited the greatest impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Impact of anti-tacking agents on properties of gas-entrapped membrane and effervescent floating tablets.

PubMed

Kriangkrai, Worawut; Puttipipatkhachorn, Satit; Sriamornsak, Pornsak; Pongjanyakul, Thaned; Sungthongjeen, Srisagul

2014-12-01

Tackiness caused by the gas-entrapped membrane (Eudragit(®)RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the film. Addition and increasing amount of anti-tacking agents lowered the film mechanical strength, but the coating films were still strong and flexible enough to resist the generated gas pressure inside the floating tablet. Wettability and water vapor permeability of the film decreased with increasing level of anti-tacking agents as a result of their hydrophobicity. No interaction between anti-tacking agents and polymer was observed as confirmed by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry studies. Increasing amount of anti-tacking agents decreased time to float and tended to retard drug release of the floating tablets. Floating properties and drug release were also influenced by type of anti-tacking agents. The obtained floating tablets still possessed good floating properties and controlled drug release even though anti-tacking agent had some effects. The results demonstrated that the tackiness problem of the floating tablets could be solved by incorporating anti-tacking agent into the gas-entrapped membrane.

Research data collection methods: from paper to tablet computers.

PubMed

Wilcox, Adam B; Gallagher, Kathleen D; Boden-Albala, Bernadette; Bakken, Suzanne R

2012-07-01

Primary data collection is a critical activity in clinical research. Even with significant advances in technical capabilities, clear benefits of use, and even user preferences for using electronic systems for collecting primary data, paper-based data collection is still common in clinical research settings. However, with recent developments in both clinical research and tablet computer technology, the comparative advantages and disadvantages of data collection methods should be determined. To describe case studies using multiple methods of data collection, including next-generation tablets, and consider their various advantages and disadvantages. We reviewed 5 modern case studies using primary data collection, using methods ranging from paper to next-generation tablet computers. We performed semistructured telephone interviews with each project, which considered factors relevant to data collection. We address specific issues with workflow, implementation and security for these different methods, and identify differences in implementation that led to different technology considerations for each case study. There remain multiple methods for primary data collection, each with its own strengths and weaknesses. Two recent methods are electronic health record templates and next-generation tablet computers. Electronic health record templates can link data directly to medical records, but are notably difficult to use. Current tablet computers are substantially different from previous technologies with regard to user familiarity and software cost. The use of cloud-based storage for tablet computers, however, creates a specific challenge for clinical research that must be considered but can be overcome.

Mold with improved core for metal casting operation

DOEpatents

Gritzner, Verne B.; Hackett, Donald W.

1977-01-01

The present invention is directed to a mold containing an improved core for use in casting hollow, metallic articles. The core is formed of, or covered with, a layer of cellular material which possesses sufficient strength to maintain its structural integrity during casting, but will crush to alleviate the internal stresses that build up if the normal contraction during solidification and cooling is restricted.

Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

NASA Astrophysics Data System (ADS)

Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

2018-02-01

Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

A study on friability, hardness and fiber content analysis of fiber enriched milk tablet

NASA Astrophysics Data System (ADS)

Suzihaque, M. U. H.; Irfan, M. H.; Ibrahim, U. K.

2017-06-01

This study was performed to analyze the friability, hardness and fiber content of fiber enriched milk tablet derived from five different local fiber sources such as carrot, spinach, dragon fruit, mango and watermelon. Cow milk was mixed to complement with the tablet as a protein source. The powder were spray dried at 100°C, 120°C and 140°C and freeze dried at -60°C. The mixture of fruits and milk were made into equal ratio with the addition of 15 maltodextrin as a carrier. Tablets formed were used for friability and hardness test while dried powder were used for fiber content analysis. Dragon fruit tablet dried at 140°C have the highest friability with 11. 42 of weight loss. The second highest friability was spinach tablet dried at 100°C and 120°C drying temp erature with 9.30 and 9.28 respectively. The lowest friability was exhibited by carrot, mango and watermelon tablet at 100°C and dragon fruit at 120°C while carrot and spinach at 140°C. In contras t, none of the freeze dried tablets showed any weight loss hence they are not friable. For hardness test, all of the freeze dried showed to have higher tensile strength than spray dried, where carrot showed to be the highest at 2.27 Newton and the lowest were spray dried mango at 0.16 Newton. In fiber content analysis, freeze dried mango have the highest fiber content followed by freeze dried carrot and 140°C s pray dried carrot. It can be concluded that the higher the spray dry temperature, the more friable is the tablet. While, high friability leads to lower hardness of tablets. In terms of fiber content, the higher the spray dry temperature, the lower the fiber content found.

The Influence of High Drug Loading in Xanthan Tablets and Media with Different Physiological pH and Ionic Strength on Swelling and Release.

PubMed

Mikac, Urša; Sepe, Ana; Baumgartner, Saša; Kristl, Julijana

2016-03-07

The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on them. It is interesting that the matrix swelling is primarily regulated by Xan despite high drug loading (25%, 50%). The gastric pH and high ionic strength of the media do not influence the position of the penetration and swelling fronts but do affect the erosion front and gel thickness. The different release profiles obtained in mixing and nonmixing in vitro methods are the consequence of matrix hydration level and erosion at the surface. In water and in diluted acid medium with low ionic strength, the main release mechanism is erosion, whereas in other media (pH 1.2, μ ≥ 0.20 M), anomalous transport dominates as was found out by fitting of measured data with theoretical model. Besides the in vitro investigation that mimics gastric conditions, mathematical modeling makes the product development more successful.

Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

PubMed

Karkossa, Frank; Klein, Sandra

2017-10-01

The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

Efficacy of afoxolaner plus milbemycin oxime chewable tablets (NexGard Spectra®, Merial) against adult Ancylostoma ceylanicum hookworm, in dogs.

PubMed

Tielemans, E; Lebon, W; Dumont, P; Taweethavonsawat, P; Larsen, D; Rehbein, S

2017-04-30

A fixed-combination chewable tablet incorporating afoxolaner plus milbemycin oxime (NexGard Spectra ® , Merial) was tested in purpose-bred Beagle dogs for efficacy against adult Ancylostoma ceylanicum hookworms. Sixteen dogs were inoculated each by oral administration of approximately 500 infective larvae of A. ceylanicum. Seventeen days after inoculation, the dogs were weighed and allocated randomly to be treated with afoxolaner plus milbemycin oxime chewable tablets or to remain untreated. Commercial chewable tablets of different strength were combined to deliver doses as close as possible to the minimum effective dose of 2.5mg afoxolaner plus 0.5mg milbemycin oxime per kg body weight. Parasites were recovered and counted for determination of efficacy seven days after treatment. All eight dogs that had been left untreated were harboring adult A. ceylanicum (geometric mean, 317.8; range, 210-428) while only one and nine A. ceylanicum were recovered from two of the eight dogs treated with afoxolaner plus milbemycin oxime chewable tablets (geometric mean, 0.5; p<0.0001). Thus, 99.9% efficacy against induced infection of A. ceylanicum was obtained by the use of oral NexGard Spectra ® at the minimum effective dose. Treatment with afoxolaner plus milbemycin oxime chewable tablets was well accepted and safe. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects.

PubMed

Vakkalagadda, Blisse; Vetter, Marion L; Rana, Jignasa; Smith, Charles H; Huang, Jian; Karkas, Jennifer; Boulton, David W; LaCreta, Frank

2015-12-01

Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed-dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open-label, randomized, single-dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of C max, AUC 0-T, and AUC inf of both analytes were between 0.80 and 1.25. Seventy-two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.

Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet.

PubMed

Jung, Huijeong Ashley; Augsburger, Larry L

2012-07-01

An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab® concentration, DiPac®/Xylitab® ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability <10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab® and/or Xylitab®, magnesium stearate, and Explotab® suggested that the amount of Explotab® was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel® and Explotab®, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone® XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol® showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.

Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets.

PubMed

Khan, Shagufta; Kataria, Prashant; Nakhat, Premchand; Yeole, Pramod

2007-06-22

The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapid-disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8:2 did not show drug release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1:1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t(90), 60 seconds) in SGF compared with marketed formulation (t(90), 240 seconds; P < .01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity.

Concrete density estimation by rebound hammer method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ismail, Mohamad Pauzi bin, E-mail: pauzi@nm.gov.my; Masenwat, Noor Azreen bin; Sani, Suhairy bin

Concrete is the most common and cheap material for radiation shielding. Compressive strength is the main parameter checked for determining concrete quality. However, for shielding purposes density is the parameter that needs to be considered. X- and -gamma radiations are effectively absorbed by a material with high atomic number and high density such as concrete. The high strength normally implies to higher density in concrete but this is not always true. This paper explains and discusses the correlation between rebound hammer testing and density for concrete containing hematite aggregates. A comparison is also made with normal concrete i.e. concrete containingmore » crushed granite.« less

Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis.

PubMed

Denti, Paolo; Garcia-Prats, Anthony J; Draper, Heather R; Wiesner, Lubbe; Winckler, Jana; Thee, Stephanie; Dooley, Kelly E; Savic, Rada M; McIlleron, Helen M; Schaaf, H Simon; Hesseling, Anneke C

2018-02-01

Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwent pharmacokinetic sampling following receipt of a dose of 15 or 20 mg/kg of body weight given as a whole or crushed tablet(s) orally or via a nasogastric tube. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Model-based simulations were performed to estimate the doses across weight bands that would achieve adult exposures with 750-mg once-daily dosing. One hundred nine children were included. The median age was 2.1 years (range, 0.3 to 8.7 years), and the median weight was 12 kg (range, 6 to 22 kg). Levofloxacin followed 2-compartment kinetics with first-order elimination and absorption with a lag time. After inclusion of allometric scaling, the model characterized the age-driven maturation of clearance (CL), with the effect reaching 50% of that at maturity at about 2 months after birth and 100% of that at maturity by 2 years of age. CL in a typical child (weight, 12 kg; age, 2 years) was 4.7 liters/h. HIV infection reduced CL by 16%. By use of the adult 250-mg formulation, levofloxacin exposures were substantially lower than those reported in adults receiving a similar dose on a milligram-per-kilogram basis. To achieve adult-equivalent exposures at a 750-mg daily dose, higher levofloxacin pediatric doses of from 18 mg/kg/day for younger children with weights of 3 to 4 kg (due to immature clearance) to 40 mg/kg/day for older children may be required. The doses of levofloxacin currently recommended for the treatment of MDR-TB in children result in exposures considerably lower than those in adults. The effects of different formulations and formulation manipulation require further investigation. We recommend age- and weight-banded doses of 250-mg tablets of the adult formulation most likely to achieve target concentrations for prospective evaluation. Copyright © 2018 American Society for Microbiology.

49 CFR 587.15 - Verification of aluminum honeycomb crush strength.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., the fringes (“e”) are at least half the length of one bonded cell wall (“d”) (in the ribbon direction... width is 150 mm (5.9 in) ±6 mm (0.24 in), and the thickness is 25 mm (1 in) ±2 mm (0.08 in). The walls of incomplete cells around the edge of the sample are trimmed as follows (See Figure 3). In the width...

Use of rubble from building demolition in mortars.

PubMed

Corinaldesi, V; Giuggiolini, M; Moriconi, G

2002-01-01

Because of increasing waste production and public concerns about the environment, it is desirable to recycle materials from building demolition. If suitably selected, ground, cleaned and sieved in appropriate industrial crushing plants, these materials can be profitably used in concrete. Nevertheless, the presence of masonry instead of concrete rubble is particularly detrimental to the mechanical performance and durability of recycled-aggregate concrete and the same negative effect is detectable when natural sand is replaced by fine recycled aggregate fraction. An alternative use of both masonry rubble and fine recycled material fraction could be in mortars. These could contain either recycled instead of natural sand or powder obtained by bricks crushing as partial cement substitution. In particular, attention is focused on the modification that takes place when either polypropylene or stainless steel fibers are added to these mortars. Polypropylene fibers are added in order to reduce shrinkage of mortars, stainless steel fibers for improving their flexural strength. The combined use of polypropylene fibers and fine recycled material from building demolition could allow the preparation of mortars showing good performance, in particular when coupled with bricks. Furthermore, the combined use of stainless steel fibers and mortars containing brick powder seems to be an effective way to guarantee a high flexural strength.

Regeneration of paint sludge and reuse in cement concrete

NASA Astrophysics Data System (ADS)

Feng, Enqi; Sun, Jitao; Feng, Liming

2018-06-01

Paint Sludge (PS) is a hazardous waste. Inappropriate disposal of PS might be harmful to public health and the environment. Various size of Paint Sludge Solid Powder (PSSP) particles have been produced by automatic processing equipment via dewatering, crushing, screening removing Volatile Organic Compounds (VOCs), and etc. Meanwhile, the test results show that PSSP is not a hazardous waste. Both flexural and compressive strength are increased by adding PSSP of polyurethane to cement concrete at a level of below 10% of cement weight. However, the strength has a significant reduction at a level of above 15% of cement weight. The reason for the increase of strength is probably due to a slow coagulation and copolymerization of PSSP and cement. The reduction is likely due to the self-reunion of PSSP.

Utilisation of Waste Marble Dust as Fine Aggregate in Concrete

NASA Astrophysics Data System (ADS)

Vigneshpandian, G. V.; Aparna Shruthi, E.; Venkatasubramanian, C.; Muthu, D.

2017-07-01

Concrete is the important construction material and it is used in the construction industry due to its high compressive strength and its durability. Now a day’s various studies have been conducted to make concrete with waste material with the intention of reducing cost and unavailability of conventional materials. This paper investigates the strength properties of concrete specimens cast using waste marble dust as replacement of fine aggregate. The marble pieces are finely crushed to powdered and the gradation is compared with conventional fine aggregate. Concrete specimen were cast using wmd in the laboratory with different proportion (25%, 50% and 100%) by weight of cement and from the studies it reveals that addition of waste marble dust as a replacement of fine aggregate marginally improves compressive, tensile and flexural strength in concrete.

HIGH SHEAR GRANULATION PROCESS: ASSESSING IMPACT OF FORMULATION VARIABLES ON GRANULES AND TABLETS CHARACTERISTICS OF HIGH DRUG LOADING FORMULATION USING DESIGN OF EXPERIMENT METHODOLOGY.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Ali, Bahaa E

2017-03-01

High shear wet granulation is a significant component procedure in the pharmaceutical industry. The objective of the study was to investigate the influence of two independent formulation variables; polyvinypyrrolidone (PVP) as a binder (X,) and croscarmellose sodium (CCS) as a disintegrant (X2) on the crit- ical quality attributes of acetaminophen granules and their corresponding tablets using design of experiment (DoE) approach. A two factor, three level (32) full factorial design has been applied; each variable was investi- gated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their density, granule size and flowability. Additionally, the produced tablets have been investigated for: break- ing force, friability, disintegration time and t. of drug dissolution. The analysis of variance (ANOVA) showed that the two variables had a significant impact (p < 0.05) on granules and tablets characteristics, while only the binder concentration influenced the tablets friability. Furthermore, significant interactions (p < 0.05) between the two variables, for granules and tablets attributes, were also found. However, variables interaction showed minimal effect for granules flowability as well as tablets friability. Desirability function was carried out to opti- mize the variables under study to obtain product within the USP limit. It was found that the higher desirability (0.985) could be obtained at the medium level of PVP and low level of CCS. Ultimately, this study supplies the formulator with beneficial tools in selecting the proper level of binder and disintegrant to attain product with desired characteristics.

Investigation of the potential for direct compaction of a fine ibuprofen powder dry-coated with magnesium stearate.

PubMed

Qu, Li; Zhou, Qi Tony; Gengenbach, Thomas; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Gamlen, Michael; Morton, David A V

2015-05-01

Intensive dry powder coating (mechanofusion) with tablet lubricants has previously been shown to give substantial powder flow improvement. This study explores whether the mechanofusion of magnesium stearate (MgSt), on a fine drug powder can substantially improve flow, without preventing the powder from being directly compacted into tablets. A fine ibuprofen powder, which is both cohesive and possesses a low-melting point, was dry coated via mechanofusion with between 0.1% and 5% (w/w) MgSt. Traditional low-shear blending was also employed as a comparison. No significant difference in particle size or shape was measured following mechanofusion. For the low-shear blended powders, only marginal improvement in flowability was obtained. However, after mechanofusion, substantial improvements in the flow properties were demonstrated. Both XPS and ToF-SIMS demonstrated high degrees of a nano-scale coating coverage of MgSt on the particle surfaces from optimized mechanofusion. The study showed that robust tablets were produced from the selected mechanofused powders, at high-dose concentration and tablet tensile strength was further optimized via addition of a Polyvinylpyrrolidone (PVP) binder (10% w/w). The tablets with the mechanofused powder (with or without PVP) also exhibited significantly lower ejection stress than those made of the raw powder, demonstrating good lubrication. Surprisingly, the release rate of drug from the tablets made with the mechanofused powder was not retarded. This is the first study to demonstrate such a single-step dry coating of model drug with MgSt, with promising flow improvement, flow-aid and lubrication effects, tabletability and also non-inhibited dissolution rate.

Continuous direct compression as manufacturing platform for sustained release tablets.

PubMed

Van Snick, B; Holman, J; Cunningham, C; Kumar, A; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2017-03-15

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of sustained release tablets was crucial to ensure reproducible dissolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous manufacturing of extended release tablets via powder mixing and direct compression.

PubMed

Ervasti, Tuomas; Simonaho, Simo-Pekka; Ketolainen, Jarkko; Forsberg, Peter; Fransson, Magnus; Wikström, Håkan; Folestad, Staffan; Lakio, Satu; Tajarobi, Pirjo; Abrahmsén-Alami, Susanna

2015-11-10

The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Transmission near-infrared (NIR) and photon time-of-flight (PTOF) spectroscopy in a comparative analysis of pharmaceuticals.

PubMed

Kamran, Faisal; Abildgaard, Otto H A; Sparén, Anders; Svensson, Olof; Johansson, Jonas; Andersson-Engels, Stefan; Andersen, Peter E; Khoptyar, Dmitry

2015-03-01

We present a comprehensive study of the application of photon time-of-flight spectroscopy (PTOFS) in the wavelength range 1050-1350 nm as a spectroscopic technique for the evaluation of the chemical composition and structural properties of pharmaceutical tablets. PTOFS is compared to transmission near-infrared spectroscopy (NIRS). In contrast to transmission NIRS, PTOFS is capable of directly and independently determining the absorption and reduced scattering coefficients of the medium. Chemometric models were built on the evaluated absorption spectra for predicting tablet drug concentration. Results are compared to corresponding predictions built on transmission NIRS measurements. The predictive ability of PTOFS and transmission NIRS is comparable when models are based on uniformly distributed tablet sets. For non-uniform distribution of tablets based on particle sizes, the prediction ability of PTOFS is better than that of transmission NIRS. Analysis of reduced scattering spectra shows that PTOFS is able to characterize tablet microstructure and manufacturing process parameters. In contrast to the chemometric pseudo-variables provided by transmission NIRS, PTOFS provides physically meaningful quantities such as scattering strength and slope of particle size. The ability of PTOFS to quantify the reduced scattering spectra, together with its robustness in predicting drug content, makes it suitable for such evaluations in the pharmaceutical industry.

Comparison of neurofuzzy logic and decision trees in discovering knowledge from experimental data of an immediate release tablet formulation.

PubMed

Shao, Q; Rowe, R C; York, P

2007-06-01

Understanding of the cause-effect relationships between formulation ingredients, process conditions and product properties is essential for developing a quality product. However, the formulation knowledge is often hidden in experimental data and not easily interpretable. This study compares neurofuzzy logic and decision tree approaches in discovering hidden knowledge from an immediate release tablet formulation database relating formulation ingredients (silica aerogel, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and process variables (dwell time and compression force) to tablet properties (tensile strength, disintegration time, friability, capping and drug dissolution at various time intervals). Both approaches successfully generated useful knowledge in the form of either "if then" rules or decision trees. Although different strategies are employed by the two approaches in generating rules/trees, similar knowledge was discovered in most cases. However, as decision trees are not able to deal with continuous dependent variables, data discretisation procedures are generally required.

Applications of terahertz-pulsed technology in the pharmaceutical industry

NASA Astrophysics Data System (ADS)

Taday, Philip F.

2010-02-01

Coatings are applied to pharmaceutical tablets (or pills) to for either cosmetic or release control reasons. Cosmetic coatings control the colour or to mask the taste of an active ingredient; the thickness of these coating is not critical to the performance of the product. On the other hand the thickness and uniformity of a controlled release coating has been found affect the release of the active ingredient. In this work we have obtained from a pharmacy single brand of pantoprazole tablet and mapped them using terahertz pulsed imaging (TPI) prior to additional dissolution testing. Three terahertz parameters were derived for univariate analysis for each layer: coating thickness, terahertz electric field peak strength and terahertz interface index. These parameters were then correlated dissolution tested. The best fit was found to be with combined coating layer thickness of the inert layer and enteric coating. The commercial tablets showed a large variation in coating thickness.

Comparison studies on the percolation thresholds of binary mixture tablets containing excipients of plastic/brittle and plastic/plastic deformation properties.

PubMed

Amin, Mohd C I; Fell, John T

2004-01-01

Percolation theory has been used with great interest in understanding the design and characterization of dosage forms. In this study, work has been carried out to investigate the behavior of binary mixture tablets containing excipients of similar and different deformation properties. The binary mixture tablets were prepared by direct compression using lactose, polyvinyl chloride (PVC), Eudragit RS 100, and microcrystalline cellulose (MCC). The application of percolation theory on the relationships between compactibility, Pmax, or compression susceptibility (compressibility), gamma, and mixture compositions reveals the presence of percolation thresholds even for mixtures of similar deformation properties. The results showed that all mixture compositions exhibited at least one discreet change in the slope, which was referred to as the percolation threshold. The PVC/Eudragit RS100 mixture compositions showed significant percolation threshold at 80% (w/w) PVC loading. Two percolation thresholds were observed from a series of binary mixtures containing similar plastic deformation materials (PVC/MCC). The percolation thresholds were determined at 20% (w/w) and 80% (w/w) PVC loading. These are areas where one of the components percolates throughout the system and the properties of the tablets are expected to experience a sudden change. Experimental results, however, showed that total disruption of the tablet physical properties at the specified percolation thresholds can be observed for PVC/lactose mixtures at 20-30% (w/w) loading while only minor changes in the tablets' strength for PVC/MCC or PVC/Eudragit RS 100 mixtures were observed.

Bioequivalence of saxagliptin/metformin extended-release (XR) fixed-dose combination tablets and single-component saxagliptin and metformin XR tablets in healthy adult Chinese subjects.

PubMed

Gummesson, Anders; Li, Haiyan; Gillen, Michael; Xu, John; Niazi, Mohammad; Hirshberg, Boaz

2014-11-01

As compared with individual tablets, saxagliptin/metformin extended-release (XR) fixed-dose combination (FDC) tablets offer the potential for increased patient compliance with the convenience of once daily dosing. The aim of the present study was to show that the FDC of saxagliptin and metformin XR is bioequivalent to co-administration of the individual components when given to Chinese subjects residing in China. This was a randomized, open-label, single-dose, two-period, cross-over pharmacokinetic study in two cohorts of healthy adult Chinese male subjects (n = 32 in each cohort) under fed conditions. In cohort 1, the pharmacokinetic properties of a saxagliptin/metformin XR 5/500 mg FDC tablet were compared with those of co-administration of a 5 mg saxagliptin tablet and a 500 mg metformin XR tablet. In cohort 2, the pharmacokinetic properties of a saxagliptin/metformin XR 5/1,000 mg FDC tablet were compared with those of co-administration of a 5 mg saxagliptin tablet and 2 × 500 mg metformin XR tablets. The two cohorts were independent of each other with respect to treatment and results. The pharmacokinetic properties of the active metabolite of saxagliptin (5-hydroxy-saxagliptin), as well as the safety and tolerability of each treatment, were also evaluated. For both cohorts, saxagliptin and metformin in the FDCs were bioequivalent to the individual components, as the limits of the 90 % confidence intervals of the geometric least squares mean ratios were contained within the 80-125 % bioequivalence limits for the area under the plasma concentration-time curve parameters and within the 70-143 % bioequivalence limits for the maximum plasma concentration. Similar exposures of 5-hydroxy-saxagliptin were observed with the two treatment regimens within each cohort. Co-administration of saxagliptin and metformin XR was generally safe and well tolerated as the FDCs or as individual tablets. Saxagliptin/metformin XR 5/500 mg and saxagliptin/metformin XR 5/1,000 mg FDCs were bioequivalent to individual tablets of saxagliptin and metformin XR of the same strengths and were generally well tolerated. These results in healthy Chinese subjects are consistent with those of previous assessments of saxagliptin/metformin XR FDC in the saxagliptin clinical development programme.

Data for Prediction of Mechanical Properties of Aspen Flakeboards.

DTIC Science & Technology

1983-09-01

mat and, consequently, Design of particleboards or flakeboards with specific flexural possible flake damage by crushing. Geirner has since properties...acletst at gos U.S. Foes Produt La. ’Nire numein pernm e refe to @teW cited at end of report. ., Experimental Design and Procedute Homogeneous boards...superior tensile strength to steanInjected boards at low Bending Properties . : SG levels where the comparativ advantage of steam- "iection presg (i.e

Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

PubMed

Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2017-01-01

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (<0.1%). The melt-granulated captopril in matrix systems containing 50% EC (45P, 100P or 100FP) and the melt-granulated metformin hydrochloride in reservoir systems coated with Kollicoat® SR 30D and Opadry® II (80:20 with 10% weight gain or 70:30 with 20% weight gain) exhibited release profiles adequate to sustained release formulations, for over 450min. Therefore, carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Recyclability of Concrete Pavement Incorporating High Volume of Fly Ash.

PubMed

Yoshitake, Isamu; Ishida, Takeo; Fukumoto, Sunao

2015-08-21

Recyclable concrete pavement was made from fly ash and crushed limestone sand and gravel as aggregates so that the concrete pavement could be recycled to raw materials for cement production. With the aim to use as much fly ash as possible for the sustainable development of society, while achieving adequate strength development, pavement concrete having a cement-replacement ratio of 40% by mass was experimentally investigated, focusing on the strength development at an early age. Limestone powder was added to improve the early strength; flexural strength at two days reached 3.5 MPa, the minimum strength for traffic service in Japan. The matured fly ash concrete made with a cement content of 200 kg/m3 achieved a flexural strength almost equal to that of the control concrete without fly ash. Additionally, Portland cement made from the tested fly ash concrete was tested to confirm recyclability, with the cement quality meeting the Japanese classification of ordinary Portland cement. Limestone-based recyclable fly ash concrete pavement is, thus, a preferred material in terms of sustainability.

Recyclability of Concrete Pavement Incorporating High Volume of Fly Ash

PubMed Central

Yoshitake, Isamu; Ishida, Takeo; Fukumoto, Sunao

2015-01-01

Recyclable concrete pavement was made from fly ash and crushed limestone sand and gravel as aggregates so that the concrete pavement could be recycled to raw materials for cement production. With the aim to use as much fly ash as possible for the sustainable development of society, while achieving adequate strength development, pavement concrete having a cement-replacement ratio of 40% by mass was experimentally investigated, focusing on the strength development at an early age. Limestone powder was added to improve the early strength; flexural strength at two days reached 3.5 MPa, the minimum strength for traffic service in Japan. The matured fly ash concrete made with a cement content of 200 kg/m3 achieved a flexural strength almost equal to that of the control concrete without fly ash. Additionally, Portland cement made from the tested fly ash concrete was tested to confirm recyclability, with the cement quality meeting the Japanese classification of ordinary Portland cement. Limestone-based recyclable fly ash concrete pavement is, thus, a preferred material in terms of sustainability. PMID:28793518

[Divisibility of warfarin and fluindione tablets tested in elderly patients and their family circle].

PubMed

Pautas, Eric; Despres, Jérémie; Peyron, Isabelle; Golmard, Jean-Louis; Grange, Jennifer; Koenig, Nelly; Gouronnec, Adeline; Mitha, Nathalie; Siguret, Virginie; Gouin-Thibault, Isabelle

2011-06-01

Vitamin K antagonist tablets are often split to fractionate the dose by elderly patients. We performed a study in order to assess the divisibility of one dosage strength of score-lined warfarin and of score-lined fluindione. Due to a recent change in the pharmaceutical form of fluindione in order to improve the divisibility, the study was performed over 2 different periods (with the « old » and with the « new » pharmaceutical form). In each period, 10 patients mean aged 82 years, 10 relatives, 10 nurses, 10 medical doctors) were asked to split in half warfarin tablets (W2 1(st) period et W2 2(d) period) and fluindione tablets (F2 et F'2), and to split fluindione tablets into 4 fragments (F4 et F'4). The first end-point was the accuracy of splitting estimated by the difference between the real and the expected weight of fragmented tablets. The statistical analysis was performed using an ANOVA test with 2 variables, subject and drug. The difference between the 2 periods were analyzed using an ANOVA test with 2 variables, subject and period. Over the 2 periods, the differences between real and expected weight were of 4.65% for W2 1(st) phase, 9.48% for F2, 15.35% for F4, 5.56% for W2 2(d )period, 4.30% for F'2, and 6.98% for F'4. The quality of splitting was statistically poorer in the elderly patient group compared to other subjects. This study was not design to assess the clinical relevance (bleeding or thromboembolism) or the anticoagulation control of the variations in drug mass due to inappropriate splitting of tablets. However, split form of drugs should be prescribe with caution to elderly patients.

Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy.

PubMed

Markl, Daniel; Bawuah, Prince; Ridgway, Cathy; van den Ban, Sander; Goodwin, Daniel J; Ketolainen, Jarkko; Gane, Patrick; Peiponen, Kai-Erik; Zeitler, J Axel

2018-02-15

Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, S a , to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The S a parameter analysis was applied to three different data sets including tablets with only one excipient (functionalised calcium carbonate), samples with one excipient (microcrystalline cellulose) and one drug (indomethacin), and a complex formulation (granulated product comprising several excipients and one drug). The overall porosity, tablet thickness, initial particle size distribution as well as the granule density were all found to affect the significant structural anisotropies that were observed in all investigated tablets. The S a parameter provides new insights into the microstructure of a tablet and its potential was particularly demonstrated for the analysis of formulations comprising several components. The results clearly indicate that material attributes, such as particle size and granule density, cause a change of the pore structure, which, therefore, directly impacts the liquid imbibition that is part of the disintegration process. We show, for the first time, how the granule density impacts the pore structure, which will also affect the performance of the tablet. It is thus of great importance to gain a better understanding of the relationship of the physical properties of material attributes (e.g. intragranular porosity, particle shape), the compaction process and the microstructure of the finished product. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating.

PubMed

Kunnath, Kuriakose; Huang, Zhonghui; Chen, Liang; Zheng, Kai; Davé, Rajesh

2018-05-30

It has been shown that dry coating cohesive active pharmaceutical ingredients (APIs) with nano-silica can improve packing and flow of their blends, facilitating high speed direct compression tableting. This paper examines the broader scope and generality of previous work by examining three fine APIs; micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP) and micronized Ibuprofen (mIBU), and considers dry coating with both hydrophobic or hydrophilic nano-silica to examine the effect not only on packing density and flow of their blends, but also dissolution and tensile strength of their tablets. The impact of the excipient size on blend and tablet properties are also investigated, indicating blend flow is most improved when matching API particle size with excipient particle size. In all cases where the API is dry coated, the blend packing and flow improve, so as to suggest such high drug loaded blends could enable direct compression. Using dry coated API along with finer excipients in blends lead to improved hardness of the corresponding tablets. Interestingly, dissolution profiles show dry coated API tablets generally have faster dissolution rates, regardless of silica hydrophilicity, suggesting API powder deagglomeration via nano-silica coating plays a crucial role. The most significant conclusion is that, although there are differences in properties of blends that depend on the API, hydrophobic or hydrophilic nano-silica coating, as well as large or fine excipients, in all cases, dry coating of APIs significantly improves the possibility of using the specific blend at high drug loading in direct compression tableting. Copyright © 2018 Elsevier B.V. All rights reserved.

Microsphere Insulation Panels

NASA Technical Reports Server (NTRS)

Mohling, R.; Allen, M.; Baumgartner, R.

2006-01-01

Microsphere insulation panels (MIPs) have been developed as lightweight, longlasting replacements for the foam and vacuum-jacketed systems heretofore used for thermally insulating cryogenic vessels and transfer ducts. The microsphere core material of a typical MIP consists of hollow glass bubbles, which have a combination of advantageous mechanical, chemical, and thermal-insulation properties heretofore available only separately in different materials. In particular, a core filling of glass microspheres has high crush strength and low density, is noncombustible, and performs well in soft vacuum.

Process for Design Optimization of Honeycomb Core Sandwich Panels for Blast Load Mitigation

DTIC Science & Technology

2012-12-01

experiments. Numerical simulation using a single ‘Y’ cross-sectional unit cell model predicted the crush behavior quite well compared to experiments with...of foil glued together by an adhesive. LS-DYNA is used to carry out the virtual simulation . The foil is modeled by quadrilateral Belytschko-Tsay...aluminum alloy with bilinear isotropic-hardening elastoplastic material model is used for the foil. Since the yield and ultimate strength of the AL5052

49 CFR 587.15 - Verification of aluminum honeycomb crush strength.

Code of Federal Regulations, 2012 CFR

2012-10-01

... material being tested. Four samples, each measuring 300 mm (11.8 in) × 300 mm (11.8 in) × 25 mm (1 in.... Samples of the following size are used for testing. The length is 150 mm (5.9 in) ±6 mm (0.24 in), the width is 150 mm (5.9 in) ±6 mm (0.24 in), and the thickness is 25 mm (1 in) ±2 mm (0.08 in). The walls...

49 CFR 587.15 - Verification of aluminum honeycomb crush strength.

Code of Federal Regulations, 2013 CFR

2013-10-01

... material being tested. Four samples, each measuring 300 mm (11.8 in) × 300 mm (11.8 in) × 25 mm (1 in.... Samples of the following size are used for testing. The length is 150 mm (5.9 in) ±6 mm (0.24 in), the width is 150 mm (5.9 in) ±6 mm (0.24 in), and the thickness is 25 mm (1 in) ±2 mm (0.08 in). The walls...

49 CFR 587.15 - Verification of aluminum honeycomb crush strength.

Code of Federal Regulations, 2014 CFR

2014-10-01

... material being tested. Four samples, each measuring 300 mm (11.8 in) × 300 mm (11.8 in) × 25 mm (1 in.... Samples of the following size are used for testing. The length is 150 mm (5.9 in) ±6 mm (0.24 in), the width is 150 mm (5.9 in) ±6 mm (0.24 in), and the thickness is 25 mm (1 in) ±2 mm (0.08 in). The walls...

49 CFR 587.15 - Verification of aluminum honeycomb crush strength.

Code of Federal Regulations, 2011 CFR

2011-10-01

... material being tested. Four samples, each measuring 300 mm (11.8 in) × 300 mm (11.8 in) × 25 mm (1 in.... Samples of the following size are used for testing. The length is 150 mm (5.9 in) ±6 mm (0.24 in), the width is 150 mm (5.9 in) ±6 mm (0.24 in), and the thickness is 25 mm (1 in) ±2 mm (0.08 in). The walls...

Vocal fold paralysis: improved adductor recovery by vincristine blockade of posterior cricoarytenoid.

PubMed

Paniello, Randal C

2015-03-01

A new treatment for acute unilateral vocal-fold paralysis (UVFP) was proposed in which a drug is injected into the posterior cricoarytenoid muscle (PCA) shortly after nerve injury, before the degree of natural recovery is known, to prevent antagonistic synkinetic reinnervation. This concept was tested in a series of canine experiments using vincristine as the blocking agent. Animal experiments. Laryngeal adductor function was measured at baseline and at 6 months following experimental recurrent laryngeal nerve (RLN) injuries, including complete transection, crush injury, and cautery. In the treatment animals, the PCA was injected with vincristine at the time of RLN injury. Adductor function in the vincristine-treated hemilarynges was significantly improved compared with injury-matched noninjected controls (total n = 43). Transection/repair controls recovered 56.1% of original adductor strength; vincristine-treated hemilarynges recovered to 73.1% (P = 0.002). Cautery injuries also improved with vincristine block (60.7% vs. 88.7%; P = 0.031). Crush injuries recovered well even without vincristine (104.8% vs. 111.2%; P = 0.35). These findings support a new paradigm of early, preemptive blockade of the antagonist muscle (PCA) to improve ultimate net adductor strength, which could potentially improve functional recovery in many UVFP patients and avoid the need for medialization procedures. Possible clinical aspects of this new approach are discussed. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Role of Grain Crushing in the Alteration of Mechanical and Flow Properties of Sandstones during Mechanical Failure

NASA Astrophysics Data System (ADS)

Mirabolghasemi, M.; Prodanovic, M.; Choens, R. C., II; Dewers, T. A.

2016-12-01

We present a workflow to study the alteration of flow and mechanical characteristics of sandstones after shear failure, specifically modeling weakening of the formation due to CO2 injection. We use discrete elements method (DEM) to represent each sand grain as a cluster of bonded sub-particles, and model their potential crushing. We also introduce bonds between sand grain clusters to enable the modeling of the mechanical behavior of consolidated sandstones. The model is tuned by comparing our numerical compression tests on single sand grains with the experimental results reported in the literature. Once the mechanical behavior of individual grains is adequately captured by the model, a packing of such grains is subjected to shear stress. Once the packing fails under the imposed shear stress, its mechanical properties, permeability, and porosity are calculated. This test is repeated for various conditions by varying parameters such as the brittleness of single grains (the relative quartz-feldspar content of the grains), normal stress, and cement strength (assuming (chemical) weakening of the inter- and intra-grain-cluster bonds due to CO2 injection). We specifically compare the effect of cement/bond strength weakening on mechanical properties to triaxial compression experimental measurements before and after hydrous scCO2 and CO2-saturated brine injection in Boise sandstone performed in Sandia National Laboratory.

The use of laboratory sand, soil and crushed-glass filter columns for polishing domestic-strength synthetic wastewater that has undergone secondary treatment.

PubMed

Healy, M G; Burke, P; Rodgers, M

2010-10-01

The aim of this study was to examine the performance of intermittently loaded, 150 mm-diameter stratified filter columns of 2 depths (0.65 and 0.375 m) comprising different media--sand, crushed glass and soil--in polishing the effluent from a laboratory horizontal flow biofilm reactor (HFBR) treating synthetic domestic-strength wastewater. The HFBR has been successfully used to remove organic carbon and ammonium-nitrogen (NH4-N) from domestic wastewater. In this treatment method, wastewater is allowed to flow over and back along a stack of polyvinyl chloride (PVC) sheets. Biofilms on the sheets reduce organic carbon, suspended matter, and nutrients in the wastewater, but to achieve the quality of a septic tank system, additional treatment is required. In all filters, at a hydraulic loading rate of 100 L m(-2) d(-1), 40-65% of chemical oxygen demand (COD) and practically 100% of total suspended solids (TSS) were removed, nitrification was complete, and bacterial numbers were reduced by over 80%, with best removals achieved in the soil filters (93%). Soil polishing filters with the depth of 0.65 m performed best in terms of organic carbon, total nitrogen (Tot-N) and bacterial removal. Data from this preliminary study are useful in the design of treatment systems to polish secondary wastewaters with similar water quality characteristics.

Preparation and properties of porous microspheres made from borate glass.

PubMed

Conzone, Samuel D; Day, Delbert E

2009-02-01

Dysprosium lithium-borate glass microspheres and particles, ranging from 45 to 150 microm in diameter, were reacted with a 0.25 M phosphate solution at 37 degrees C, whose pH was either 3 or 8.8. The glass reacted nonuniformly and was converted into a porous, amorphous, hydrated, dysprosium phosphate reaction product. The amorphous product had the same volume and shape (pseudomorphic) as the unreacted glass, and could be dried without cracking. After heating at 300 degrees C for 1 h, the amorphous reaction product had a specific surface area of approximately 200 m(2)/g, a pore size of approximately 30 nm, and nominal crushing strength of approximately 10 MPa. When the reaction product was heated to 600 degrees C for 15 min, the specific surface area decreased to approximately 90 m(2)/g and the nominal crushing strength increased to 35 MPa. Heating above 615 degrees C converted the amorphous dysprosium phosphate product into crystalline DyPO(4), which contained open porosity until heated above 800 degrees C for 15 min. Highly porous materials of different chemical composition can be prepared by chemically reacting a borate-based glass with an aqueous solution at low-temperature (<100 degrees C). These highly porous materials are easy to process, and are considered candidates for controlled drug delivery, catalysis, chromatographic separation, filtration, and as bioactive materials.

Characterization of natural polymers from jackfruit pulp, calendula flowers and tara seeds as mucoadhesive and controlled release components in buccal tablets.

PubMed

Sabale, Vidya; Paranjape, Archana; Patel, Vandana; Sabale, Prafulla

2017-02-01

Identification and physiochemical parameters such as solubility, loss on drying, viscosity, pH, swelling index, starch and gum constituents were determined in natural polymers and showed satisfactory results. Spectral studies established the compatibility of natural polymers. The drug release kinetics in preliminary trial batches showed that tablets containing natural mucilages and gum showed a prolonged drug release comparable to Carbopol 974P and Methocel K4M. Also, all tablets showed a satisfactory drug permeability flux. Acute toxicity studies confirmed the safety of natural polymers. Using response surface method supported by 2 3 factorial design, the optimized buccoadhesive tablets (C1) with drug release at 8h (R8h, %) of 53.48±0.048% showed controlled release over ≥8h and followed the Korsmeyer-Peppas model with anomalous (non-Fickian) diffusion mechanism. Mucoadhesive strength was found to be 42.71±0.49g. Comparative dissolution study between prepared and marketed formulation showed that there was no significant difference in drug release profile having similarity factor 82.97. In vivo study for optimized formulation of the buccoadhesive tablets showed the better absolute bioavailability (71.26%) against the oral solution (51.22%). Histological study confirmed non-irritant nature and stability study indicated stability of the formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Solid dispersions in the development of a nimodipine floating tablet formulation and optimization by artificial neural networks and genetic programming.

PubMed

Barmpalexis, Panagiotis; Kachrimanis, Kyriakos; Georgarakis, Emanouil

2011-01-01

The present study investigates the use of nimodipine-polyethylene glycol solid dispersions for the development of effervescent controlled release floating tablet formulations. The physical state of the dispersed nimodipine in the polymer matrix was characterized by differential scanning calorimetry, powder X-ray diffraction, FT-IR spectroscopy and polarized light microscopy, and the mixture proportions of polyethylene glycol (PEG), polyvinyl-pyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), effervescent agents (EFF) and nimodipine were optimized in relation to drug release (% release at 60 min, and time at which the 90% of the drug was dissolved) and floating properties (tablet's floating strength and duration), employing a 25-run D-optimal mixture design combined with artificial neural networks (ANNs) and genetic programming (GP). It was found that nimodipine exists as mod I microcrystals in the solid dispersions and is stable for at least a three-month period. The tablets showed good floating properties and controlled release profiles, with drug release proceeding via the concomitant operation of swelling and erosion of the polymer matrix. ANNs and GP both proved to be efficient tools in the optimization of the tablet formulation, and the global optimum formulation suggested by the GP equations consisted of PEG=9%, PVP=30%, HPMC=36%, EFF=11%, nimodipine=14%. Copyright © 2010 Elsevier B.V. All rights reserved.

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

PubMed

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Anomalous trapping of noble gases during sample crushing

NASA Astrophysics Data System (ADS)

Cox, S. E.; Miller, H.; Farley, K. A.; Hofmann, F.

2017-12-01

Fine-grained mineral samples are commonly analyzed for noble gas composition. Many coarse minerals contain inclusions that require that the samples be crushed and purified before analysis. Other samples are crushed because fine-grained samples may be degassed at lower temperature. And many rocks lack coarse mineral grains entirely. Protin et al. (2016) showed that crushed fine-grained olivine absorbs He from the atmosphere and retains it under heating to at least 900 degrees. We show that the act of crushing itself is responsible for the vast majority of this trapping. Samples crushed in the presence of pure He retain 25 times as much He as samples crushed in vacuum and immediately exposed to pure helium. We tested several ways to mitigate this problem, including acid leaching and crushing under a liquid. We find that crushing samples under water is the simplest, most effective way to avoid contamination with He during crushing. This approach resulted in no significant contamination of crushed fine-grained olivine, even when the submerged crushing was conducted under a headspace of pure He. Protin, M. (2016), et al. GCA 179, 76-88.

A probabilistic mechanical model for prediction of aggregates’ size distribution effect on concrete compressive strength

NASA Astrophysics Data System (ADS)

Miled, Karim; Limam, Oualid; Sab, Karam

2012-06-01

To predict aggregates' size distribution effect on the concrete compressive strength, a probabilistic mechanical model is proposed. Within this model, a Voronoi tessellation of a set of non-overlapping and rigid spherical aggregates is used to describe the concrete microstructure. Moreover, aggregates' diameters are defined as statistical variables and their size distribution function is identified to the experimental sieve curve. Then, an inter-aggregate failure criterion is proposed to describe the compressive-shear crushing of the hardened cement paste when concrete is subjected to uniaxial compression. Using a homogenization approach based on statistical homogenization and on geometrical simplifications, an analytical formula predicting the concrete compressive strength is obtained. This formula highlights the effects of cement paste strength and aggregates' size distribution and volume fraction on the concrete compressive strength. According to the proposed model, increasing the concrete strength for the same cement paste and the same aggregates' volume fraction is obtained by decreasing both aggregates' maximum size and the percentage of coarse aggregates. Finally, the validity of the model has been discussed through a comparison with experimental results (15 concrete compressive strengths ranging between 46 and 106 MPa) taken from literature and showing a good agreement with the model predictions.

Chitin's Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments.

PubMed

Chaheen, Mohammad; Soulairol, Ian; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

2017-07-01

Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure "Py" shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Pure drug nanoparticles in tablets: what are the dissolution limitations?

NASA Astrophysics Data System (ADS)

Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye, Lin; Yun, Jimmy

2010-06-01

There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

Templates of patient brochures for the preparation, administration and safe-handling of oral chemotherapy.

PubMed

Siden, Rivka; Kem, Ravie; Ostrenga, Andrew; Nicksy, Darcy; Bernhardt, Brooke; Bartholomew, Joy

2014-06-01

The increased use of oral chemotherapy for the treatment of cancer introduces new challenges for patients and caregivers. Among them are the ability to swallow oral solid dosage forms, the proper administration of the agents and the safe-handling of chemotherapeutic drugs in the home. Since these drugs are hazardous, proper preparation, administration, and disposition introduces a variety of safety issues. The increased toxicity of these drugs coupled with complicated dosing regimens and the occasional need to dilute the drug or measure a liquid dosage form require careful instruction of the patient and/or caregivers. The purpose of this project was to create templates for writing patient instruction brochures. A group of clinicians specializing in oncology from several institutions in the United States and Canada met through a series of conference calls. The group included pharmacists with a specialty in pediatric oncology, investigational drug pharmacists, and an oncology nurse practitioner. National guidelines and practices at each institution were used for the creation of templates to be used in developing templates for medication and formulation-specific instruction brochures. The group developed six templates. The templates ranged in scope from instructions on the administration of intact tablets or capsules to directions on opening capsules or crushing tablets and mixing the content with foods or liquids. Thirty-three drug-specific brochures were developed using the templates. Templates of patient brochures and drug-specific brochures on the safe handling of chemotherapy in the home can be created using a collaborative, multi-institutional approach.

Prediction of reinforced concrete strength by ultrasonic velocities

NASA Astrophysics Data System (ADS)

Sabbağ, Nevbahar; Uyanık, Osman

2017-06-01

This study was aimed to determine the strength of the reinforced concrete and to reveal the reinforcement effect on the concrete strength by Ultrasonic P and S wave velocities. Studies were conducted with prepared 9 different concrete designs of showing low, medium and high strength features. 4 kinds of cubic samples which unreinforced and including 10, 14 or 20 mm diameter reinforcement were prepared for these designs. Studies were carried out on total 324 samples including 9 samples for each design of these 4 kinds. The prepared samples of these designs were subjected to water curing. On some days of the 90-day period, P and S wave measurements were repeated to reveal the changes in seismic velocities of samples depending on whether reinforced or unreinforced of samples and diameter of reinforcement. Besides, comparisons were done by performing uniaxial compressive strength test with crushing of 3 samples on 7th, 28th and 90th days. As a result of studies and evaluations, it was seen that values of seismic velocities and uniaxial compressive strength increased depending on reinforcement and diameter of reinforcement in low strength concretes. However, while the seismic velocities were not markedly affected from reinforcement or reinforcement diameter in high strength concrete, uniaxial compressive strength values were negatively affected.

Anthocyanin yield and skin softening during maceration, as affected by vineyard row orientation and grape ripeness of Vitis vinifera L. cv. Shiraz.

PubMed

Giacosa, Simone; Marengo, Fabio; Guidoni, Silvia; Rolle, Luca; Hunter, Jacobus J

2015-05-01

Anthocyanin and mechanical properties were evaluated on Shiraz grapes, picked from both sides of North-South and East-West vineyard row orientations at two harvest dates. Wines were made from each combination. The evaluation and evolution of crushed skin mechanical properties during maceration-fermentation, as also affected by grape ripeness, are shown for the first time. No significant differences in anthocyanin content were found in the grapes between the two vineyard row orientations. However, a significant decrease in anthocyanins and berry skin break force (also referred as skin hardness or strength) was found between the two harvest dates. During maceration, a reduction in the crushed berry skin break force of more than 15% occurred. The intact berries and macerated skins showed similarity in skin break energy values. The anthocyanin profile of the grapes and of the wines prominently displayed malvidin forms, changed mainly by the ripeness level of the grapes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of moisture content on the flowability of crushed ores

NASA Astrophysics Data System (ADS)

Cabrejos, Francisco

2017-06-01

In many mining and industrial processes where large quantities of non-degrading bulk materials such as crushed ores are handled, silos, hoppers, stockpiles and chutes are widely used because they are economical and reliable (if properly designed and operated). However, they are not free of trouble and may experience flow problems such as arching, ratholing, erratic flow, limited storage capacity, limited discharge flow rate, caking, segregation and/or flooding. Moisture content and fine particles significantly affect the flowability of most ores, increasing their cohesive strength and turning them more prone to these problems. The purpose of this article is to highlight a proven, scientific method that can be utilized to ensure reliable storage, flow and discharge of bulk solids in these equipment based on Jenike's flow-of-solids theory and laboratory testing. Knowledge of the flow properties of the material handled provides a design basis to ensure mass flow, avoid arching and prevent the formation of "ratholes". The effect of an increase in water content of the ore is discussed with experimental results.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PubMed

Lebin, Jacob A; Murphy, David L; Severtson, Stevan Geoffrey; Bau, Gabrielle E; Dasgupta, Nabarun; Dart, Richard C

2018-05-15

Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price. Copyright © 2018 John Wiley & Sons, Ltd.

Effect of formulation and process variables on lipid based sustained release tablets via continuous twin screw granulation: A comparative study.

PubMed

Kallakunta, Venkata Raman; Tiwari, Roshan; Sarabu, Sandeep; Bandari, Suresh; Repka, Michael A

2018-05-14

The current study's aim is to prepare lipid based sustained release tablets via a twin-screw granulation technique and compare those dosage forms with conventional techniques, namely wet granulation and direct compression. The granules were successfully manufactured in a single-step, continuous twin-screw granulation process with a low proportion of binder (Klucel™ EF, HPC SSL) using Compritol® 888 ATO, Precirol® ATO 5 and Geleol™ as sustained release agents. The granules prepared showed good flow characteristics and compaction properties. DSC and XRD studies were conducted to characterize the granules prepared via a twin-screw granulation method and the results demonstrated the crystalline nature of lipids within the granules. FTIR data indicated that there were no interactions with the formulation components investigated. The formulations developed by all three methods were compressed into tablets with a mechanical strength of 14-16 KP. The tablets formulated were characterized for physicochemical properties, in vitro drug release studies, water uptake and erosion studies. These results showed that the drug was not completely released after 24 h for tablets developed by the wet granulation process using all three lipids. The tablets prepared by the direct compression method demonstrated a burst release within 8 to 10 h from Precirol ATO 5® and Geleol™ formulations compared to Compritol® 888 ATO. However, tablets prepared using twin-screw granulation exhibited sustained release of the drug over 24 h and the water uptake and erosion results were in accordance with dissolution data. Stability data for 45 days at accelerated conditions (40 °C/75% RH) showed similar release profiles with ƒ2 values above 50 for all of the twin screw granulation formulations, indicating the suitability of the process for formulating sustained release tablets. These findings of a single-step, continuous twin-screw granulation process are novel and demonstrate new opportunities for development of sustained release tablets. Copyright © 2017. Published by Elsevier B.V.

Crush Testing at Oak Ridge National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feldman, Matthew R

2011-01-01

The dynamic crush test is required in the certification testing of some small Type B transportation packages. International Atomic Energy Agency regulations state that the test article must be 'subjected to a dynamic crush test by positioning the specimen on the target so as to suffer maximum damage.' Oak Ridge National Laboratory (ORNL) Transportation Technologies Group performs testing of Type B transportation packages, including the crush test, at the National Transportation Research Center in Knoxville, Tennessee (United States). This paper documents ORNL's experiences performing crush tests on several different Type B packages. ORNL has crush tested five different drum-type packagemore » designs, continuing its 60 year history of RAM package testing. A total of 26 crush tests have been performed in a wide variety of package orientations and crush plate CG alignments. In all cases, the deformation of the outer drum created by the crush test was significantly greater than the deformation damage caused by the 9 m drop test. The crush test is a highly effective means for testing structural soundness of smaller nondense Type B shipping package designs. Further regulatory guidance could alleviate the need to perform the crush test in a wide range of orientations and crush plate CG alignments.« less

Potential applicability of stress wave velocity method on pavement base materials as a non-destructive testing technique

NASA Astrophysics Data System (ADS)

Mahedi, Masrur

Aggregates derived from natural sources have been used traditionally as the pavement base materials. But in recent times, the extraction of these natural aggregates has become more labor intensive and costly due to resource depletion and environmental concerns. Thus, the uses of recycled aggregates as the supplementary of natural aggregates are increasing considerably in pavement construction. Use of recycled aggregates such as recycled crushed concrete (RCA) and recycled asphalt pavement (RAP) reduces the rate of natural resource depletion, construction debris and cost. Although recycled aggregates could be used as a viable alternative of conventional base materials, strength characteristics and product variability limit their utility to a great extent. Hence, their applicability is needed to be evaluated extensively based on strength, stiffness and cost factors. But for extensive evaluation, traditionally practiced test methods are proven to be unreasonable in terms of time, cost, reliability and applicability. On the other hand, rapid non-destructive methods have the potential to be less time consuming and inexpensive along with the low variability of test results; therefore improving the reliability of estimated performance of the pavement. In this research work, the experimental program was designed to assess the potential application of stress wave velocity method as a non-destructive test in evaluating recycled base materials. Different combinations of cement treated recycled concrete aggregate (RAP) and recycled crushed concrete (RCA) were used to evaluate the applicability of stress wave velocity method. It was found that, stress wave velocity method is excellent in characterizing the strength and stiffness properties of cement treated base materials. Statistical models, based on P-wave velocity were derived for predicting the modulus of elasticity and compressive strength of different combinations of cement treated RAP, Grade-1 and Grade-2 materials. Two, three and four parameter modeling were also done for characterizing the resilient modulus response. It is anticipated that, derived correlations can be useful in estimating the strength and stiffness response of cement treated base materials with satisfactory level of confidence, if the P-wave velocity remains within the range of 500 ft/sec to 1500 ft/sec.

The Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Three year effects on pQCT bone mineral density and strength measures in postmenopausal women

PubMed Central

SHEDD-WISE, KRISTINE M.; ALEKEL, D. LEE; HOFMANN, HEIKE; HANSON, KATHY B.; SCHIFERL, DAN J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined two soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (via peripheral quantitative computed tomography) in healthy postmenopausal women (46–63 y). We measured 3 y change in cortical (Ct) BMD, cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171) and trabecular (Tb) BMD, PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. Strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120 mg/d was protective of CtBMD. Strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80 mg/d became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3 y was modestly beneficial for midshaft femur vBMD as TLMP increased, and for midshaft femur SSI as bone turnover increased. PMID:21295742

Preconstruction Engineering and Design Phase Reevaluation Report, Olcott Harbor Project, Olcott, New York. Volume 2, Supporting Documentation. Revision.

DTIC Science & Technology

1992-09-01

85 (saturated) : 0 : 26 3. Cell Fill (crushed stone) : 110 (moist) : 0 : 32 68 ( submerged ) 4. Breakwater Armor Stone : 110 (moist) : 0 40 68... submerged ) 5. Queenston Shale bedrock : unconfined compressive strength : au = 6,000 psi 7 5. PROJECT FEATURES FOR FINAL DESIGN a. Breakwaters. The project...existing conrete pad (550 feet from the retaining wall) the structure is submerged with isolated portions of the structure observable at the lake

Automation for Crushing and Screening Equipment to Produce Graded Paving Crushed Stone

NASA Astrophysics Data System (ADS)

Tikhonov, Anatoly; Velichkin, Vladimir

2017-10-01

This paper offers analysis of factors related to production and storage of graded crushed stone, which adversely impact the service life and wear resistance of asphalt-concrete motor road pavements. The paper describes external and technology-related parameters that may cause changes of the preset ratio in graded crushed stone. Control factors are described that ensure the formulated fraction ratio in crushed stone by controlling the operation mode of the crushing and screening equipment. The paper also contains an ACS flow chart for crushing and screening equipment engaged in continuous closed-cycle two-stage technology. Performance of the ACS to maintain the preset fractionated crushed stone ratio has been confirmed with a mathematical model.

The effect of wall thickness distribution on mechanical reliability and strength in unidirectional porous ceramics.

PubMed

Seuba, Jordi; Deville, Sylvain; Guizard, Christian; Stevenson, Adam J

2016-01-01

Macroporous ceramics exhibit an intrinsic strength variability caused by the random distribution of defects in their structure. However, the precise role of microstructural features, other than pore volume, on reliability is still unknown. Here, we analyze the applicability of the Weibull analysis to unidirectional macroporous yttria-stabilized-zirconia (YSZ) prepared by ice-templating. First, we performed crush tests on samples with controlled microstructural features with the loading direction parallel to the porosity. The compressive strength data were fitted using two different fitting techniques, ordinary least squares and Bayesian Markov Chain Monte Carlo, to evaluate whether Weibull statistics are an adequate descriptor of the strength distribution. The statistical descriptors indicated that the strength data are well described by the Weibull statistical approach, for both fitting methods used. Furthermore, we assess the effect of different microstructural features (volume, size, densification of the walls, and morphology) on Weibull modulus and strength. We found that the key microstructural parameter controlling reliability is wall thickness. In contrast, pore volume is the main parameter controlling the strength. The highest Weibull modulus ([Formula: see text]) and mean strength (198.2 MPa) were obtained for the samples with the smallest and narrowest wall thickness distribution (3.1 [Formula: see text]m) and lower pore volume (54.5%).

The effect of wall thickness distribution on mechanical reliability and strength in unidirectional porous ceramics

NASA Astrophysics Data System (ADS)

Seuba, Jordi; Deville, Sylvain; Guizard, Christian; Stevenson, Adam J.

2016-01-01

Macroporous ceramics exhibit an intrinsic strength variability caused by the random distribution of defects in their structure. However, the precise role of microstructural features, other than pore volume, on reliability is still unknown. Here, we analyze the applicability of the Weibull analysis to unidirectional macroporous yttria-stabilized-zirconia (YSZ) prepared by ice-templating. First, we performed crush tests on samples with controlled microstructural features with the loading direction parallel to the porosity. The compressive strength data were fitted using two different fitting techniques, ordinary least squares and Bayesian Markov Chain Monte Carlo, to evaluate whether Weibull statistics are an adequate descriptor of the strength distribution. The statistical descriptors indicated that the strength data are well described by the Weibull statistical approach, for both fitting methods used. Furthermore, we assess the effect of different microstructural features (volume, size, densification of the walls, and morphology) on Weibull modulus and strength. We found that the key microstructural parameter controlling reliability is wall thickness. In contrast, pore volume is the main parameter controlling the strength. The highest Weibull modulus (?) and mean strength (198.2 MPa) were obtained for the samples with the smallest and narrowest wall thickness distribution (3.1 ?m) and lower pore volume (54.5%).

The effects of crushing speed on the energy-absorption capability of composite material

NASA Technical Reports Server (NTRS)

Farley, Gary L.

1987-01-01

The energy-absorption capability as a function of crushing speed was determined for Thornel 300/Fiberite 934 (Gr/E) and Kevlar-49/Fiberite 934 (K/E) composite material. Circular cross section tube specimens were crushed at quasi-static, 6 m/sec, and 12 m/sec speeds. Ply orientations of the tube specimens were (0/+ or - theta) sub 2 and (+ or - theta) sub 3 where theta=15, 45, and 75 degress. Based on the results of these tests the energy-absortion capability of Gr/E and K/E was determined to be a function of crushing speed. The crushing modes based on exterior appearance of the crushed tubes were unchanged for either material. However, the interlaminar crushing behavior changed with crushing speed.

Latent structure modeling underlying theophylline tablet formulations using a Bayesian network based on a self-organizing map clustering.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2015-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and design space. In this article, we integrate thin-plate spline (TPS) interpolation, Kohonen's self-organizing map (SOM) and a Bayesian network (BN) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared using a standard formulation. We measured the tensile strength and disintegration time as response variables and the compressibility, cohesion and dispersibility of the pretableting blend as latent variables. We predicted these variables quantitatively using nonlinear TPS, generated a large amount of data on pretableting blends and tablets and clustered these data into several clusters using a SOM. Our results show that we are able to predict the experimental values of the latent and response variables with a high degree of accuracy and are able to classify the tablet data into several distinct clusters. In addition, to visualize the latent structure between the causal and latent factors and the response variables, we applied a BN method to the SOM clustering results. We found that despite having inserted latent variables between the causal factors and response variables, their relation is equivalent to the results for the SOM clustering, and thus we are able to explain the underlying latent structure. Consequently, this technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulation.

Bioequivalence studies for 2 different strengths of irbesartan/hydrochlorothiazide combination in healthy volunteers: 300/25 mg and 300/12.5 mg film-coated tablets.

PubMed

Cánovas, M; Cabré, F; Polonio, F

2014-05-01

Two bioequivalence studies of irbesartan (CAS 138402-11-6) and hydrochlorothiazide (CAS 58-93-5) combination at 300/12.5 mg and 300/25 mg strengths were carried out in order to assess the bioequivalence of these film-coated tablet formulations in comparison with the marketed reference formulations.Both studies were performed with 30 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. In each study, test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 72 h following drug administration in case of irbesartan and up to 24 h in case of hydrochlorothiazide. Plasma concentrations of both analytes were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference).For both studies, the 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t [(irbesartan: 300/12.5 mgstrength: 95.33-111.74%. 300/25 mg strength: 91.27-103.93%) (hydrochlorothiazide: 300/12.5 mg strength: 99.63-107.50%. 300/25 mg strength: 95.72-102.24%)] and Cmax [(irbesartan: 300/12.5 mg strength: 98.73-115.03%. 300/25 mg strength: 97.27-112.12%) (hydrochlorothiazide: 300/12.5 mg strength: 97.34-112.06%. 300/25 mg strength: 93.29-106.38%)] were within the bio-equivalence acceptance range of 80-125%.According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that both test formulations are bioequivalent to the corresponding reference formulations. Overall, it was judged that both studies were conducted with a good tolerance of the subjects to study drugs. © Georg Thieme Verlag KG Stuttgart · New York.

Working with Enzymes - Where Is Lactose Digested? An Enzyme Assay for Nutritional Biochemistry Laboratories

NASA Astrophysics Data System (ADS)

Pope, Sandi R.; Tolleson, Tonya D.; Williams, R. Jill; Underhill, Russell D.; Deal, S. Todd

1998-06-01

At Georgia Southern University, we offer a sophomore-level introductory biochemistry course that is aimed at nutrition and chemistry education majors. The laboratory portion of this course has long lacked an experimental introduction to enzymes. We have developed a simple enzyme assay utilizing lactase enzyme from crushed LactAid tablets and a 5% lactose solution ("synthetic milk"). In the experiment, the students assay the activity of the enzyme on the "synthetic milk" at pHs of approximately 1, 6, and 8 with the stated goal of determining where lactose functions in the digestive tract. The activity of the lactase may be followed chromatographically or spectrophotometrically. The experiment, which is actually a simple pH assay, is easily implemented in allied health chemistry laboratory courses and readily lends itself to adaptation for more complex kinetic assays in upper-level biochemistry laboratory courses. The experimental details, including a list of required supplies and hints for implementation, are provided.

Having and Being an Other-Sex Crush during Early Adolescence

ERIC Educational Resources Information Center

Bowker, Julie C.; Spencer, Sarah V.; Thomas, Katelyn K.; Gyoerkoe, Elizabeth A.

2012-01-01

This study examined other-sex crush experiences (both having and being perceived as an other-sex crush) among 544 young adolescents (mean age = 12.74 years). Results indicated that 56% had at least one current other-sex crush, with little overlap between crushes, friends, and boyfriends/girlfriends. Significant associations between other-sex crush…

Dual release and molecular mechanism of bilayered aceclofenac tablet using polymer mixture.

PubMed

Van Nguyen, Hien; Nguyen, Van Hong; Lee, Beom-Jin

2016-12-30

The objectives of the present study were to develop a controlled-release bilayered tablet of aceclofenac (AFN) 200mg with dual release and to gain a mechanistic understanding of the enhanced sustained release capability achieved by utilizing a binary mixture of the sustained release materials. Different formulations of the sustained-release layer were formulated by employing hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) as the major retarding polymers. The in vitro dissolution studies of AFN bilayered tablets were carried out in intestinal fluid (pH 6.8 buffer). The mechanism of the synergistic rate-retarding effect of the polymer mixture containing HPC and carbomer was elucidated by the rate of swelling and erosion in intestinal fluid and the molecular interactions in the polymer network. The optimized bilayered tablets had similar in vitro dissolution profiles to the marketed tablet Clanza ® CR based on the similarity factor (f2) in combination with their satisfactory micromeritic, physicochemical properties, and stability profiles. Drug release from HPMC-based matrix was controlled by non-Fickian transport, while drug release from HPC-based matrix was solely governed by drug diffusion. The swelling and erosion data exhibited a dramatic increase of water uptake and a reduction of weight loss in the polymer mixture-loaded tablet. Fourier transform infrared (FTIR) spectra revealed strong hydrogen bonding between HPC and carbomer in the polymer mixture. Regarding spatial distribution of polymers in the polymer mixture-loaded tablet, carbomer was found to be the main component of the gel layer during the first 2h of the hydration process, which was responsible for retarding drug release at initial stage. This process was then followed by a gradual transition of HPC from the glassy core to the gel layer for further increasing gel strength. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

Effect of sorbed water on disintegrant performance of four brands of Polacrilin Potassium NF.

PubMed

Bele, Mrudula H; Derle, Diliprao V

2012-03-01

Polacrilin Potassium NF is a commonly used weak cation exchange resin disintegrant in pharmaceutical tablets. The objective of this research was to evaluate the effects of sorbed moisture on physical characteristics and disintegrant performance of four brands of Polacrilin Potassium NF. The disintegrants were stored in five different relative humidity chambers and their dynamic vapor adsorption-desorption analysis, effect of moisture on their compressibility, compactability, particle size, morphology, water uptake rate, and disintegration ability were studied. Moisture seemed to plasticize the disintegrants, reducing their yield pressures. However, certain optimum amount of moisture was found to be useful in increasing the compactablity of the tablets containing disintegrants. The tablets, however, lost their tensile strengths beyond this optimum moisture content. Moisture caused two brands of the disintegrants to swell; however, two other brands aggregated upon exposure to moisture. Swelling without aggregation increased the water uptake, and in turn the disintegrant performance. However, aggregation probably reduced the porosities of the disintegrants, reducing their water uptake rate and disintegrant performance. Different brands of Polacrilin Potassium NF differed in the abilities to withstand the effects of moisture on their functionality. Effect of moisture on disintegrant performance of Polacrilin Potassium NF needs to be considered before its use in tablets made by wet granulation.

Complementing anatomy education using three-dimensional anatomy mobile software applications on tablet computers.

PubMed

Lewis, T L; Burnett, B; Tunstall, R G; Abrahams, P H

2014-04-01

Anatomy has traditionally been a cornerstone of medical education, which has been taught via dissection and didactic lectures. The rising prevalence of mobile tablet technology means medical software applications ("apps") play an increasingly important role in medical education. The applications highlighted in this article will aid anatomical educators to identify which are the most useful in clinical, academic, and educational environments. These have been systematically identified by downloading all applications with keywords related to anatomy and then carrying out qualitative assessment. Novel anatomy applications from developers such as Visible Body, 3D4Medical, and Pocket Anatomy allow students to visualize and manipulate complex anatomical structures using detailed 3D models. They often contain additional content including clinical correlations and a range of media from instructional videos to interactive quiz functions. The strength of tablet technology lies in its ability to consolidate and present anatomical information to the user in the most appropriate manner for their learning style. The only question mark remains over the level of detail and accuracy of these applications. Innovative medical educators who embrace tablet technology will find that anatomy applications serve as a useful learning tool when used in conjunction with existing teaching setups. Copyright © 2013 Wiley Periodicals, Inc.

Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.

PubMed

Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

2015-06-01

The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30 s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15 s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5 min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution.

Physicochemical and tablet properties of Cyperus alulatus rhizomes starch granules.

PubMed

Paramakrishnan, N; Jha, S; Kumar, K Jayaram

2015-05-01

The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for its physicochemical, morphological and tableting properties. Rhizomes of CA yield a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was characterized in terms of moisture, ash and amylose contents, solubility and swelling power, paste clarity and water retention capacity. The swelling power was found to be significantly improved with the increase in temperature. Scanning electron micrographs revealed that the granule's surface was smooth, the granules were spherical, mostly round, disc like, and the size range was 6.65-12.13 μm. Finger print region in FTIR spectra confirmed its carbohydrate nature. The evaluated micromeritic properties of extracted granule's bulk density, tapped density, Carr's index, Hausner ratio, true density and porosity render unique practicability of CASG being used as an adjuvant in pharmaceutical solid dosage forms. Tablets prepared by using CASG showed higher mechanical strength and more disintegration time, which depicted the characteristic binding nature of the starch granules. As CASG is imparting better binding properties in less concentration and also it can be used in combination with the established starches to get the synergistic effect; this starch can be used commercially in the tablet preparation. Copyright © 2015 Elsevier B.V. All rights reserved.

High performance of treated and washed MSWI bottom ash granulates as natural aggregate replacement within earth-moist concrete.

PubMed

Keulen, A; van Zomeren, A; Harpe, P; Aarnink, W; Simons, H A E; Brouwers, H J H

2016-03-01

Municipal solid waste incineration bottom ash was treated with specially designed dry and wet treatment processes, obtaining high quality bottom ash granulate fractions (BGF) suitable for up to 100% replacement of natural gravel in concrete. The wet treatment (using only water for separating and washing) significantly lowers the leaching of e.g. chloride and sulfate, heavy metals (antimony, molybdenum and copper) and dissolved organic carbon (DOC). Two potential bottom ash granulate fractions, both in compliance with the standard EN 12620 (aggregates for concrete), were added into earth-moist concrete mixtures. The fresh and hardened concrete physical performances (e.g. workability, strength and freeze-thaw) of high strength concrete mixtures were maintained or improved compared with the reference mixtures, even after replacing up to 100% of the initial natural gravel. Final element leaching of monolithic and crushed granular state BGF containing concretes, showed no differences with the gravel references. Leaching of all mixtures did not exceed the limit values set by the Dutch Soil Quality Degree. In addition, multiple-life-phase emission (pH static test) for the critical elements of input bottom ash, bottom ash granulate (BGF) and crushed BGF containing concrete were assessed. Simulation pH lowering or potential carbonation processes indicated that metal (antimony, barium, chrome and copper) and sulfate element leaching behavior are mainly pH dominated and controlled, although differ in mechanism and related mineral abundance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Commercial off-the-Shelf (COTS) Refractory Material Evaluation

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Kolody, Mark R.; Curran, Jerome P.; Back, Teddy; Hintze, Paul E.; Parlier, Christopher R.; Sampson, Jeffrey W.; Perusich, Stephen; Bucherl, Cori

2009-01-01

Fondu Fyre (FF) is currently the only refractory material qualified for use in the flame trench at KSC's Shuttle Launch Pads 39A and 39B. However, the material is not used as it was qualified and has undergone increasingly frequent and severe degradation due to the launch blasts. This degradation is costly as well as dangerous for launch infrastructure, crew and vehicle. FF is applied at the pad via the gunnite process, where wetted refractory material is sprayed onto a steel grid mounted on a support structure. The water content in this process can be manually adjusted by operators, causing distinct visual and physical discrepancies among repair areas. Since the application process is unlikely to change for new refractory materials, it is important to understand the effects of water content on commercial off-the-shelf (COTS) refractory materials. The purpose of this study was to evaluate the performance of the FF with respect to various water contents as well as heat treatments, to simulate aging and exposure to the blast. Initial results indicated that different water contents and heat treatments result in distinct differences in crushing strength, apparent porosity and bulk density. However, water content became an insignificant factor in both crush strength and porosity when FF was cured to at least 1500 deg. Additionally, inspection of the material's surface microstructure by scanning electron microscopy indicated distinguishable characteristics for different heat treatment levels. Results from this study will help guide future studies on the development and identification of new refractory materials.

Advanced Process Possibilities in Friction Crush Welding of Aluminum, Steel, and Copper by Using an Additional Wire

NASA Astrophysics Data System (ADS)

Besler, Florian A.; Grant, Richard J.; Schindele, Paul; Stegmüller, Michael J. R.

2017-12-01

Joining sheet metal can be problematic using traditional friction welding techniques. Friction crush welding (FCW) offers a high speed process which requires a simple edge preparation and can be applied to out-of-plane geometries. In this work, an implementation of FCW was employed using an additional wire to weld sheets of EN AW5754 H22, DC01, and Cu-DHP. The joint is formed by bringing together two sheet metal parts, introducing a wire into the weld zone and employing a rotating disk which is subject to an external force. The requirements of the welding preparation and the fundamental process variables are shown. Thermal measurements were taken which give evidence about the maximum temperature in the welding center and the temperature in the periphery of the sheet metals being joined. The high welding speed along with a relatively low heat input results in a minimal distortion of the sheet metal and marginal metallurgical changes in the parent material. In the steel specimens, this FCW implementation produces a fine grain microstructure, enhancing mechanical properties in the region of the weld. Aluminum and copper produced mean bond strengths of 77 and 69 pct to that of the parent material, respectively, whilst the steel demonstrated a strength of 98 pct. Using a wire offers the opportunity to use a higher-alloyed additional material and to precisely adjust the additional material volume appropriate for a given material alignment and thickness.

Recycling of Reinforced Plastics

NASA Astrophysics Data System (ADS)

Adams, R. D.; Collins, Andrew; Cooper, Duncan; Wingfield-Digby, Mark; Watts-Farmer, Archibald; Laurence, Anna; Patel, Kayur; Stevens, Mark; Watkins, Rhodri

2014-02-01

This work has shown is that it is possible to recycle continuous and short fibre reinforced thermosetting resins while keeping almost the whole of the original material, both fibres and matrix, within the recyclate. By splitting, crushing hot or cold, and hot forming, it is possible to create a recyclable material, which we designate a Remat, which can then be used to remanufacture other shapes, examples of plates and tubes being demonstrated. Not only can remanufacturing be done, but it has been shown that over 50 % of the original mechanical properties, such as the E modulus, tensile strength, and interlaminar shear strength, can be retained. Four different forms of composite were investigated, a random mat Glass Fibre Reinforced Plastic (GFRP) bathroom component and boat hull, woven glass and carbon fibre cloth impregnated with an epoxy resin, and unidirectional carbon fibre pre-preg. One of the main factors found to affect composite recyclability was the type of resin matrix used in the composite. Thermoset resins tested were shown to have a temperature range around the Glass Transition Temperature (Tg) where they exhibit ductile behaviour, hence aiding reforming of the material. The high-grade carbon fibre prepreg was found to be less easy to recycle than the woven of random fibre laminates. One method of remanufacturing was by heating the Remat to above its glass transition temperature, bending it to shape, and then cooling it. However, unless precautions are taken, the geometric form may revert. This does not happen with the crushed material.

Warming influences Mg2+ content, while warming and acidification influence calcification and test strength of a sea urchin.

PubMed

Byrne, Maria; Smith, Abigail M; West, Samantha; Collard, Marie; Dubois, Philippe; Graba-landry, Alexia; Dworjanyn, Symon A

2014-11-04

We examined the long-term effects of near-future changes in temperature and acidification on skeletal mineralogy, thickness, and strength in the sea urchin Tripneustes gratilla reared in all combinations of three pH (pH 8.1, 7.8, 7.6) and three temperatures (22 °C, 25 °C, 28 °C) from the early juvenile to adult, over 146 days. As the high-magnesium calcite of the echinoderm skeleton is a biomineral form highly sensitive to acidification, and influenced by temperature, we documented the MgCO3 content of the spines, test plates, and teeth. The percentage of MgCO3 varied systematically, with more Mg2+ in the test and spines. The percentage of MgCO3 in the test and teeth, but not the spines increased with temperature. Acidification did not change the percentage MgCO3. Test thickness increased with warming and decreased at pH 7.6, with no interaction between these factors. In crushing tests live urchins mostly ruptured at sutures between the plates. The force required to crush a live urchin was reduced in animals reared in low pH conditions but increased in those reared in warm conditions, a result driven by differences in urchin size. It appears that the interactive effects of warming and acidification on the Mg2+ content and protective function of the sea urchin skeleton will play out in a complex way as global climatic change unfolds.

Dynamic Response and Residual Helmet Liner Crush Using Cadaver Heads and Standard Headforms.

PubMed

Bonin, S J; Luck, J F; Bass, C R; Gardiner, J C; Onar-Thomas, A; Asfour, S S; Siegmund, G P

2017-03-01

Biomechanical headforms are used for helmet certification testing and reconstructing helmeted head impacts; however, their biofidelity and direct applicability to human head and helmet responses remain unclear. Dynamic responses of cadaver heads and three headforms and residual foam liner deformations were compared during motorcycle helmet impacts. Instrumented, helmeted heads/headforms were dropped onto the forehead region against an instrumented flat anvil at 75, 150, and 195 J. Helmets were CT scanned to quantify maximum liner crush depth and crush volume. General linear models were used to quantify the effect of head type and impact energy on linear acceleration, head injury criterion (HIC), force, maximum liner crush depth, and liner crush volume and regression models were used to quantify the relationship between acceleration and both maximum crush depth and crush volume. The cadaver heads generated larger peak accelerations than all three headforms, larger HICs than the International Organization for Standardization (ISO), larger forces than the Hybrid III and ISO, larger maximum crush depth than the ISO, and larger crush volumes than the DOT. These significant differences between the cadaver heads and headforms need to be accounted for when attempting to estimate an impact exposure using a helmet's residual crush depth or volume.

Designing nacre-like materials for simultaneous stiffness, strength and toughness: Optimum materials, composition, microstructure and size

NASA Astrophysics Data System (ADS)

Barthelat, Francois

2014-12-01

Nacre, bone and spider silk are staggered composites where inclusions of high aspect ratio reinforce a softer matrix. Such staggered composites have emerged through natural selection as the best configuration to produce stiffness, strength and toughness simultaneously. As a result, these remarkable materials are increasingly serving as model for synthetic composites with unusual and attractive performance. While several models have been developed to predict basic properties for biological and bio-inspired staggered composites, the designer is still left to struggle with finding optimum parameters. Unresolved issues include choosing optimum properties for inclusions and matrix, and resolving the contradictory effects of certain design variables. Here we overcome these difficulties with a multi-objective optimization for simultaneous high stiffness, strength and energy absorption in staggered composites. Our optimization scheme includes material properties for inclusions and matrix as design variables. This process reveals new guidelines, for example the staggered microstructure is only advantageous if the tablets are at least five times stronger than the interfaces, and only if high volume concentrations of tablets are used. We finally compile the results into a step-by-step optimization procedure which can be applied for the design of any type of high-performance staggered composite and at any length scale. The procedure produces optimum designs which are consistent with the materials and microstructure of natural nacre, confirming that this natural material is indeed optimized for mechanical performance.

Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends

PubMed Central

Siddam, Haritha; Kotla, Niranjan G.; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh

2016-01-01

Introduction: Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Methods: Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. Results: The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. Conclusion: The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability. PMID:27051631

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

PubMed

Shedd-Wise, Kristine M; Alekel, D Lee; Hofmann, Heike; Hanson, Kathy B; Schiferl, Dan J; Hanson, Laura N; Van Loan, Marta D

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Crush testing, characterizing, and modeling the crashworthiness of composite laminates

NASA Astrophysics Data System (ADS)

Garner, David Michael, Jr.

Research in the field of crashworthiness of composite materials is presented. A new crush test method was produced to characterize the crush behavior of composite laminates. In addition, a model of the crush behavior and a method for rank ordering the energy absorption capability of various laminates were developed. The new crush test method was used for evaluating the crush behavior of flat carbon/epoxy composite specimens at quasi-static and dynamic rates. The University of Utah crush test fixture was designed to support the flat specimen against catastrophic buckling. A gap, where the specimen is unsupported, allowed unhindered crushing of the specimen. In addition, the specimen's failure modes could be clearly observed during crush testing. Extensive crush testing was conducted wherein the crush force and displacement data were collected to calculate the energy absorption, and high speed video was captured during dynamic testing. Crush tests were also performed over a range of fixture gap heights. The basic failure modes were buckling, crack growth, and fracture. Gap height variations resulted in poorly, properly, and overly constrained specimens. In addition, guidelines for designing a composite laminate for crashworthiness were developed. Modeling of the crush behavior consisted of the delamination and fracture of a single ply or group of like plies during crushing. Delamination crack extension was modeled using the mode I energy release rate, G lc, where an elastica approach was used to obtain the strain energy. Variations in Glc were briefly explored with double cantilever beam tests wherein crack extension occurred along a multidirectional ply interface. The model correctly predicted the failure modes for most of the test cases, and offered insight into how the input parameters affect the model. The ranking method related coefficients of the laminate and sublaminate stiffness matrices, the ply locations within the laminate, and the laminate thickness. The ranking method correctly ordered the laminates tested in this study with respect to their energy absorption.

Evaluating vertical concentration profile of carbon source released from slow-releasing carbon source tablets and in situ biological nitrate denitrification activity

NASA Astrophysics Data System (ADS)

Yeum, Y.; HAN, K.; Yoon, J.; Lee, J. H.; Song, K.; Kang, J. H.; Park, C. W.; Kwon, S.; Kim, Y.

2017-12-01

Slow-releasing carbon source tablets were manufactured during the design of a small-scale in situ biological denitrification system to reduce high-strength nitrate (> 30 mg N/L) from a point source such as livestock complexes. Two types of slow-releasing tablets, precipitating tablet (PT, apparent density of 2.0 g/mL) and floating tablet (FT), were prepared to achieve a vertically even distribution of carbon source (CS) in a well and an aquifer. Hydroxypropyl methylcellulose (HPMC) was used to control the release rate, and microcrystalline cellulose pH 101 (MCC 101) was added as a binder. The #8 sand was used as a precipitation agent for the PTs, and the floating agents for the FTs were calcium carbonate and citric acid. FTs floated within 30 min. and remained in water because of the buoyance from carbon dioxide, which formed during the acid-base reaction between citric acid and calcium carbonate. The longevities of PTs with 300 mg of HPMC and FTs with 400 mg of HPMC were 25.4 days and 37.3 days, respectively. We assessed vertical CS profile in a continuous flowing physical aquifer model (release test, RT) and its efficiency on biological nitrate denitrification (denitrification test, DT). During the RT, PTs, FTs and a tracer (as 1 mg rhodamine B/L) were initially injected into a well of physical aquifer model (PAM). Concentrations of CS and the tracer were monitored along the streamline in the PAM to evaluate vertical profile of CS. During the DT, the same experiment was performed as RT, except continuous injection of solution containing 30 mg N/L into the PAM to evaluate biological denitrification activity. As a result of RT, temporal profiles of CS were similar at 3 different depths of monitoring wells. These results suggest that simultaneous addition of PT and FT be suitable for achieving a vertically even distribution of the CS in the injection well and an aquifer. In DT, similar profile of CS was detected in the injection well, and nitrate was biologically denitrified at downstream of the injection well. In conclusion, addition of PT and FT into a well under natural gradient condition may be an effective means for remediating high-strength nitrate in groundwater.

Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

PubMed

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-11-01

Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Retrospective chart review. Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Intranasal Hydrocodone-Acetaminophen Abuse Induced Necrosis of the Nasal Cavity and Pharynx

PubMed Central

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-01-01

Objectives Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid trans mucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Study Design Retrospective chart review. Methods Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. Results The majority of patients will initially deny the behavior frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented with one resulting in death. Conclusions The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue that can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Study Design Chart review, level of evidence: 4 PMID:22965281

Oral Medicines for Children in the European Paediatric Investigation Plans

PubMed Central

van Riet – Nales, Diana A.; Römkens, Erwin G. A. W.; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F. A. M.; Egberts, Toine C. G.; Rademaker, Carin M. A.

2014-01-01

Introduction Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. Methods All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. Results A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. Conclusion The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound. PMID:24897509

Oral medicines for children in the European paediatric investigation plans.

PubMed

van Riet-Nales, Diana A; Römkens, Erwin G A W; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F A M; Egberts, Toine C G; Rademaker, Carin M A

2014-01-01

Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound.

Sorbent Structural Testing on Carbon Dioxide Removal Sorbents for Advanced Exploration Systems

NASA Technical Reports Server (NTRS)

Watson, David; Knox, James C.; West, Phillip; Bush, Richard

2016-01-01

Long term space missions require carbon dioxide removal systems that can function with minimal downtime required for maintenance, low power consumption and maximum efficiency for CO2 removal. A major component of such a system are the sorbents used for the CO2 and desiccant beds. Sorbents must not only have adequate CO2 and H2O removal properties, but they must have the mechanical strength to prevent structural breakdown due to pressure and temperature changes during operation and regeneration, as well as resistance to breakdown due to moisture in the system from cabin air. As part of the studies used to select future CO2 sorbent materials, mechanical tests are performed on various zeolite sorbents to determine mechanical performance while dry and at various humidified states. Tests include single pellet crush, bulk crush and attrition tests. We have established a protocol for testing sorbents under dry and humid conditions, and previously tested the sorbents used on the International Space Station carbon dioxide removal assembly. This paper reports on the testing of a series of commercial sorbents considered as candidates for use on future exploration missions.

Effect of porphobilinogen on the formation of garlic green pigments.

PubMed

Mou, Conghua; Hao, Xiaoran; Xu, Zhixiang; Qiao, Xuguang

2013-08-15

Garlic (Allium sativum L.) bulb is processed into various forms such as crushed garlic, garlic juice, granules, dehydrated garlic pieces and garlic powder. However, greening is often a major problem when garlic is crushed, since it affects the appearance and quality of the resulting product. Therefore study of the formation mechanism of garlic green pigments is very important for garlic processing. The effect of porphobilinogen (PBG) on the formation of garlic green pigments was investigated in this study. As the storage time increased, there was a significant positive correlation between garlic greening and PBG content at low temperature (4 °C). PBG content decreased significantly during the garlic greening process. When treated with respiration inhibitor, both garlic greening strength and PBG content decreased as the concentration of respiration inhibitor increased. The green colour was generated when extracted PBG and allicin mixed thoroughly. There was a clear relationship between PBG content and garlic greening. As a provider of pyrrolyl compounds, PBG plays an important role in the formation of garlic green pigments. © 2013 Society of Chemical Industry.

Strain-rate effect on initial crush stress of irregular honeycomb under dynamic loading and its deformation mechanism

NASA Astrophysics Data System (ADS)

Wang, Peng; Zheng, Zhijun; Liao, Shenfei; Yu, Jilin

2018-02-01

The seemingly contradictory understandings of the initial crush stress of cellular materials under dynamic loadings exist in the literature, and a comprehensive analysis of this issue is carried out with using direct information of local stress and strain. Local stress/strain calculation methods are applied to determine the initial crush stresses and the strain rates at initial crush from a cell-based finite element model of irregular honeycomb under dynamic loadings. The initial crush stress under constant-velocity compression is identical to the quasi-static one, but less than the one under direct impact, i.e. the initial crush stresses under different dynamic loadings could be very different even though there is no strain-rate effect of matrix material. A power-law relation between the initial crush stress and the strain rate is explored to describe the strain-rate effect on the initial crush stress of irregular honeycomb when the local strain rate exceeds a critical value, below which there is no strain-rate effect of irregular honeycomb. Deformation mechanisms of the initial crush behavior under dynamic loadings are also explored. The deformation modes of the initial crush region in the front of plastic compaction wave are different under different dynamic loadings.

DOE Office of Scientific and Technical Information (OSTI.GOV)

B.Kh. Bulaevskii; V.S. Shved; Yu.V. Kalimin

A new coke-sorting system has been introduced at OAO Koks. It differs from the existing system in that it has no bunkers for all-purpose coke but only bunkers for commercial coke. In using this system with coke from battery 4, the crushing of the coke on conveyer belts, at roller screens, and in the commercial-coke bunkers is studied. After installing braking elements in the coke path, their effectiveness in reducing coke disintegration and improving coke screening is investigated. The granulometric composition and strength of the commercial coke from coke battery 3, with the new coke-sorting system, is evaluated.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Wei-Yang

Foam materials are used to protect sensitive components from impact loading. In order to predict and simulate the foam performance under various loading conditions, a validated foam model is needed and the mechanical properties of foams need to be characterized. Uniaxial compression and tension tests were conducted for different densities of foams under various temperatures and loading rates. Crush stress, tensile strength, and elastic modulus were obtained. A newly developed confined compression experiment provided data for investigating the foam flow direction. A biaxial tension experiment was also developed to explore the damage surface of a rigid polyurethane foam.

Evaluation of methods to estimate missing days' supply within pharmacy data of the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN).

PubMed

Lum, Kirsten J; Newcomb, Craig W; Roy, Jason A; Carbonari, Dena M; Saine, M Elle; Cardillo, Serena; Bhullar, Harshvinder; Gallagher, Arlene M; Lo Re, Vincent

2017-01-01

The extent to which days' supply data are missing in pharmacoepidemiologic databases and effective methods for estimation is unknown. We determined the percentage of missing days' supply on prescription and patient levels for oral anti-diabetic drugs (OADs) and evaluated three methods for estimating days' supply within the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN). We estimated the percentage of OAD prescriptions and patients with missing days' supply in each database from 2009 to 2013. Within a random sample of prescriptions with known days' supply, we measured the accuracy of three methods to estimate missing days' supply by imputing the following: (1) 28 days' supply, (2) mode number of tablets/day by drug strength and number of tablets/prescription, and (3) number of tablets/day via a machine learning algorithm. We determined incidence rates (IRs) of acute myocardial infarction (AMI) using each method to evaluate the impact on ascertainment of exposure time and outcomes. Days' supply was missing for 24 % of OAD prescriptions in CPRD and 33 % in THIN (affecting 48 and 57 % of patients, respectively). Methods 2 and 3 were very accurate in estimating days' supply for OADs prescribed at a consistent number of tablets/day. Method 3 was more accurate for OADs prescribed at varying number of tablets/day. IRs of AMI were similar across methods for most OADs. Missing days' supply is a substantial problem in both databases. Method 2 is easy and very accurate for most OADs and results in IRs comparable to those from method 3.

Rapidly disintegrating tablets containing taste masked metoclopramide hydrochloride prepared by extrusion-precipitation method.

PubMed

Randale, Shivsagar Ashok; Dabhi, Chandu Somatbhai; Tekade, Avinash Ramrao; Belgamwar, Veena Shailendra; Gattani, Surendra Ganeshlal; Surana, Sanjay Javarilal

2010-04-01

The purpose of this study was to mask the intensely bitter taste of metoclopramide HCl and to formulate a rapid disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing metoclopramide HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratio by the extrusion-precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.8, taste evaluation in oral cavity and molecular property. The complex having drug-polymer ratio of 1 : 2 shows significant taste masking, confirmed by drug release in SSF and in-vivo taste evaluation; therefore, it was selected for further study. Taste evaluation of DPCs in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) within 10 s, whereas, metoclopramide HCl was rated intensely bitter with a score of +3 for 10 s. Tablets were evaluated for various parameters like tensile strength, wetting time, water absorption ratio, in-vitro disintegration time, and disintegration in oral cavity. The effect of diluents, lubricants and sweetening agent (Xylisorb) on the disintegration time was also evaluated. Tablets of batch F3 containing mannitol and microcrystalline cellulose in the ratio 1 : 1 and 8% w/w crosspovidone showed faster disintegration (within 20 s) than the marketed formulation (180 s). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Tablets of batch F3 also revealed rapid drug release (t(90), 90 s) in SGF compared with marketed formulation (t(90), 600 s).

Discrete element modeling of microstructure of nacre

NASA Astrophysics Data System (ADS)

Chandler, Mei Qiang; Cheng, Jing-Ru C.

2018-04-01

The microstructure of nacre consists of polygon-shaped aragonite mineral tablets bonded by very thin layers of organic materials and is organized in a brick-mortar morphology. In this research, the discrete element method was utilized to model this structure. The aragonite mineral tablets were modeled with three-dimensional polygon particles generated by the Voronoi tessellation method to represent the Voronoi-like patterns of mineral tablets assembly observed in experiments. The organic matrix was modeled with a group of spring elements. The constitutive relations of the spring elements were inspired from the experimental results of organic molecules from the literature. The mineral bridges were modeled with simple elastic bonds with the parameters based on experimental data from the literature. The bulk stress-strain responses from the models agreed well with experimental results. The model results show that the mineral bridges play important roles in providing the stiffness and yield strength for the nacre, while the organic matrix in providing the ductility for the nacre. This work demonstrated the suitability of particle methods for modeling microstructures of nacre.

Application of halloysite clay nanotubes as a pharmaceutical excipient.

PubMed

Yendluri, Raghuvara; Otto, Daniel P; De Villiers, Melgardt M; Vinokurov, Vladimir; Lvov, Yuri M

2017-04-15

Halloysite nanotubes, a biocompatible nanomaterial of 50-60nm diameter and ca. 15nm lumen, can be used for loading, storage and sustained release of drugs either in its pristine form or with additional polymer complexation for extended release time. This study reports the development composite tablets based on 50wt.% of the drug loaded halloysite mixed with 45wt.% of microcrystalline cellulose. Powder flow and compressibility properties of halloysite (angle of repose, Carr's index, Hausner ratio, Brittle Fracture Index, tensile strength) indicate that halloysite is an excellent tablet excipient. Halloysite tubes can also be filled with nifedipine with ca. 6wt.% loading efficiency and sustained release from the nanotubes. Tablets prepared with drug loaded halloysite allowed for almost zero order nifedipine release for up to 20h. Nifedipine trapped in the nanotubes also protect the drug against light and significantly increased the photostability of the drug. All of these demonstrate that halloysite has the potential to be an excellent pharmaceutical excipient that is also an inexpensive, natural and abundantly available material. Copyright © 2017 Elsevier B.V. All rights reserved.

A numerical approach to model and predict the energy absorption and crush mechanics within a long-fiber composite crush tube

NASA Astrophysics Data System (ADS)

Pickett, Leon, Jr.

Past research has conclusively shown that long fiber structural composites possess superior specific energy absorption characteristics as compared to steel and aluminum structures. However, destructive physical testing of composites is very costly and time consuming. As a result, numerical solutions are desirable as an alternative to experimental testing. Up until this point, very little numerical work has been successful in predicting the energy absorption of composite crush structures. This research investigates the ability to use commercially available numerical modeling tools to approximate the energy absorption capability of long-fiber composite crush tubes. This study is significant because it provides a preliminary analysis of the suitability of LS-DYNA to numerically characterize the crushing behavior of a dynamic axial impact crushing event. Composite crushing theory suggests that there are several crushing mechanisms occurring during a composite crush event. This research evaluates the capability and suitability of employing, LS-DYNA, to simulate the dynamic crush event of an E-glass/epoxy cylindrical tube. The model employed is the composite "progressive failure model", a much more limited failure model when compared to the experimental failure events which naturally occur. This numerical model employs (1) matrix cracking, (2) compression, and (3) fiber breakage failure modes only. The motivation for the work comes from the need to reduce the significant cost associated with experimental trials. This research chronicles some preliminary efforts to better understand the mechanics essential in pursuit of this goal. The immediate goal is to begin to provide deeper understanding of a composite crush event and ultimately create a viable alternative to destructive testing of composite crush tubes.

31. VIEW FROM SOUTHWEST TO CORNER WHERE SAMPLING/CRUSHING ADDITIONS ABUT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

31. VIEW FROM SOUTHWEST TO CORNER WHERE SAMPLING/CRUSHING ADDITIONS ABUT CRUSHED OXIDIZED ORE BIN. INTACT BARREN SOLUTION TANK VISIBLE IN FRONT OF CRUSHED ORE BIN. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

The Effects of Phrenic Nerve Degeneration by Axotomy and Crush on the Electrical Activities of Diaphragm Muscles of Rats.

PubMed

Alkiş, Mehmet Eşref; Kavak, Servet; Sayır, Fuat; Him, Aydin

2016-03-01

The aim of this study was to investigate the effect of axotomy and crush-related degeneration on the electrical activities of diaphragm muscle strips of experimental rats. In the present study, twenty-one male Wistar-albino rats were used and divided into three groups. The animals in the first group were not crushed or axotomized and served as controls. Phrenic nerves of the rats in the second and third groups were crushed or axotomized in the diaphragm muscle. Resting membrane potential (RMP) was decreased significantly in both crush and axotomy of diaphragm muscle strips of experimental rats (p < 0.05). Depolarization time (T DEP) and half-repolarization (1/2 RT) time were significantly prolonged in crush and axotomy rats (p < 0.05). Crushing or axotomizing the phrenic nerves may produce electrical activities in the diaphragm muscle of the rat by depolarization time and half-repolarization time prolonged in crush and axotomy rats.

Enhanced Mechanical Properties of 316L Stainless Steel Prepared by Aluminothermic Reaction Subjected to Multiple Warm Rolling

NASA Astrophysics Data System (ADS)

Li, Z. N.; Wei, F. A.; La, P. Q.; Ma, F. L.

2018-05-01

Large dimensional bulk 316L stainless steels were prepared by aluminothermic reaction method and rolled at 973 K (700 °C) with different deformation, the microstructures evolution and mechanical properties were characterized in detail. The results showed that the microstructure of casting steel consists of nanocrystalline/submicrocrystalline/microcrystalline austenite and submicrocrystalline ferrite. After rolling to thickness reduction of 30, 50 and 70%, the submicrocrystalline austenite grains were crushed and dispersed more uniformly in the matrix of the steel, the grain size of submicrocrystalline austenite decreased from 246 to 136 nm. The mechanical properties of the rolled steels were significantly enhanced, with the thickness reduction increased from 30 to 70%, the tensile strength increased from 632 to 824 MPa, the yield strength increased from 425 to 615 MPa, and the elongation increased from 11 to 24%. After rolling to thickness reduction of 70%, the optimized combination of high strength and high ductility was obtained.

Reuse of industrial sludge as construction aggregates.

PubMed

Tay, J H; Show, K Y; Hong, S Y

2001-01-01

Industrial wastewater sludge and dredged marine clay are high volume wastes that needed enormous space at landfill disposal sites. Due to the limitation of land space, there is an urgent need for alternative disposal methods for these two wastes. This study investigates the possibility of using the industrial sludge in combination with marine clay as construction aggregates. Different proportions of sludge and clay were made into round and angular aggregates. It was found that certain mix proportions could provide aggregates of adequate strength, comparable to that of conventional aggregates. Concrete samples cast from the sludge-clay aggregates yield compressive strengths in the range of 31.0 to 39.0 N/mm2. The results showed that the round aggregates of 100% sludge and the crush aggregates of sludge with up to 20% clay produced concrete of compressive strengths which are superior to that of 38.0 N/mm2 for conventional aggregate. The study indicates that the conversion of high volume wastes into construction materials is a potential option for waste management.

Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

PubMed

Heiman, Johanna; Tajarobi, Farhad; Gururajan, Bindhumadhavan; Juppo, Anne; Abrahmsén-Alami, Susanna

2015-04-01

The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing).

How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

PubMed

Hancock, Bruno C; Garcia-Munoz, Salvador

2013-03-01

Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data. The data from the PQRI industry survey do not support the commonly held viewpoint that granulation processes are necessary to create and sustain tablet and capsule formulations with a high degree of API uniformity. There was no correlation between the blend or tablet potency variability and the type of process used to manufacture the product. Although it is commonly believed that direct compression processes should be avoided for low API loading formulations because of blend and tablet content uniformity concerns, the data for direct compression processes reported by the respondents to the PQRI survey suggest that such processes are being used routinely to manufacture solid dosage forms of acceptable quality even when the drug loading is quite low. Copyright © 2012 Wiley Periodicals, Inc.

Atomic layer deposition-A novel method for the ultrathin coating of minitablets.

PubMed

Hautala, Jaana; Kääriäinen, Tommi; Hoppu, Pekka; Kemell, Marianna; Heinämäki, Jyrki; Cameron, David; George, Steven; Juppo, Anne Mari

2017-10-05

We introduce atomic layer deposition (ALD) as a novel method for the ultrathin coating (nanolayering) of minitablets. The effects of ALD coating on the tablet characteristics and taste masking were investigated and compared with the established coating method. Minitablets containing bitter tasting denatonium benzoate were coated by ALD using three different TiO 2 nanolayer thicknesses (number of deposition cycles). The established coating of minitablets was performed in a laboratory-scale fluidized-bed apparatus using four concentration levels of aqueous Eudragit ® E coating polymer. The coated minitablets were studied with respect to the surface morphology, taste masking capacity, in vitro disintegration and dissolution, mechanical properties, and uniformity of content. The ALD thin coating resulted in minimal increase in the dimensions and weight of minitablets in comparison to original tablet cores. Surprisingly, ALD coating with TiO 2 nanolayers decreased the mechanical strength, and accelerated the in vitro disintegration of minitablets. Unlike previous studies, the studied levels of TiO 2 nanolayers on tablets were also inadequate for effective taste masking. In summary, ALD permits a simple and rapid method for the ultrathin coating (nanolayering) of minitablets, and provides nanoscale-range TiO 2 coatings on porous minitablets. More research, however, is needed to clarify its potential in tablet taste masking applications. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of motorcycle helmet fit on estimating head impact kinematics from residual liner crush.

PubMed

Bonin, Stephanie J; Gardiner, John C; Onar-Thomas, Arzu; Asfour, Shihab S; Siegmund, Gunter P

2017-09-01

Proper helmet fit is important for optimizing head protection during an impact, yet many motorcyclists wear helmets that do not properly fit their heads. The goals of this study are i) to quantify how a mismatch in headform size and motorcycle helmet size affects headform peak acceleration and head injury criteria (HIC), and ii) to determine if peak acceleration, HIC, and impact speed can be estimated from the foam liner's maximum residual crush depth or residual crush volume. Shorty-style helmets (4 sizes of a single model) were tested on instrumented headforms (4 sizes) during linear impacts between 2.0 and 10.5m/s to the forehead region. Helmets were CT scanned to quantify residual crush depth and volume. Separate linear regression models were used to quantify how the response variables (peak acceleration (g), HIC, and impact speed (m/s)) were related to the predictor variables (maximum crush depth (mm), crush volume (cm 3 ), and the difference in circumference between the helmet and headform (cm)). Overall, we found that increasingly oversized helmets reduced peak headform acceleration and HIC for a given impact speed for maximum residual crush depths less than 7.9mm and residual crush volume less than 40cm 3 . Below these levels of residual crush, we found that peak headform acceleration, HIC, and impact speed can be estimated from a helmet's residual crush. Above these crush thresholds, large variations in headform kinematics are present, possibly related to densification of the foam liner during the impact. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suitability of river delta sediment as proppant, Missouri and Niobrara Rivers, Nebraska and South Dakota, 2015

USGS Publications Warehouse

Zelt, Ronald B.; Hobza, Christopher M.; Burton, Bethany L.; Schaepe, Nathaniel J.; Piatak, Nadine

2017-11-16

Sediment management is a challenge faced by reservoir managers who have several potential options, including dredging, for mitigation of storage capacity lost to sedimentation. As sediment is removed from reservoir storage, potential use of the sediment for socioeconomic or ecological benefit could potentially defray some costs of its removal. Rivers that transport a sandy sediment load will deposit the sand load along a reservoir-headwaters reach where the current of the river slackens progressively as its bed approaches and then descends below the reservoir water level. Given a rare combination of factors, a reservoir deposit of alluvial sand has potential to be suitable for use as proppant for hydraulic fracturing in unconventional oil and gas development. In 2015, the U.S. Geological Survey began a program of researching potential sources of proppant sand from reservoirs, with an initial focus on the Missouri River subbasins that receive sand loads from the Nebraska Sand Hills. This report documents the methods and results of assessments of the suitability of river delta sediment as proppant for a pilot study area in the delta headwaters of Lewis and Clark Lake, Nebraska and South Dakota. Results from surface-geophysical surveys of electrical resistivity guided borings to collect 3.7-meter long cores at 25 sites on delta sandbars using the direct-push method to recover duplicate, 3.8-centimeter-diameter cores in April 2015. In addition, the U.S. Geological Survey collected samples of upstream sand sources in the lower Niobrara River valley.At the laboratory, samples were dried, weighed, washed, dried, and weighed again. Exploratory analysis of natural sand for determining its suitability as a proppant involved application of a modified subset of the standard protocols known as American Petroleum Institute (API) Recommended Practice (RP) 19C. The RP19C methods were not intended for exploration-stage evaluation of raw materials. Results for the washed samples are not directly applicable to evaluations of suitability for use as fracture sand because, except for particle-size distribution, the API-recommended practices for assessing proppant properties (sphericity, roundness, bulk density, and crush resistance) require testing of specific proppant size classes. An optical imaging particle-size analyzer was used to make measurements of particle-size distribution and particle shape. Measured samples were sieved to separate the dominant-size fraction, and the separated subsample was further tested for roundness, sphericity, bulk density, and crush resistance.For the bulk washed samples collected from the Missouri River delta, the geometric mean size averaged 0.27 millimeters (mm), 80 percent of the samples were predominantly sand in the API 40/70 size class, and 17 percent were predominantly sand in the API 70/140 size class. Distributions of geometric mean size among the four sandbar complexes were similar, but samples collected from sandbar complex B were slightly coarser sand than those from the other three complexes. The average geometric mean sizes among the four sandbar complexes ranged only from 0.26 to 0.30 mm. For 22 main-stem sampling locations along the lower Niobrara River, geometric mean size averaged 0.26 mm, an average of 61 percent was sand in the API 40/70 size class, and 28 percent was sand in the API 70/140 size class. Average composition for lower Niobrara River samples was 48 percent medium sand, 37 percent fine sand, and about 7 percent each very fine sand and coarse sand fractions. On average, samples were moderately well sorted.Particle shape and strength were assessed for the dominant-size class of each sample. For proppant strength, crush resistance was tested at a predetermined level of stress (34.5 megapascals [MPa], or 5,000 pounds-force per square inch). To meet the API minimum requirement for proppant, after the crush test not more than 10 percent of the tested sample should be finer than the precrush dominant-size class. For particle shape, all samples surpassed the recommended minimum criteria for sphericity and roundness, with most samples being well-rounded. For proppant strength, of 57 crush-resistance tested Missouri River delta samples of 40/70-sized sand, 23 (40 percent) were interpreted as meeting the minimum criterion at 34.5 MPa, or 5,000 pounds-force per square inch. Of 12 tested samples of 70/140-sized sand, 9 (75 percent) of the Missouri River delta samples had less than 10 percent fines by volume following crush testing, achieving the minimum criterion at 34.5 MPa. Crush resistance for delta samples was strongest at sandbar complex A, where 67 percent of tested samples met the 10-percent fines criterion at the 34.5-MPa threshold. This frequency was higher than was indicated by samples from sandbar complexes B, C, and D that had rates of 50, 46, and 42 percent, respectively. The group of sandbar complex A samples also contained the largest percentages of samples dominated by the API 70/140 size class, which overall had a higher percentage of samples meeting the minimum criterion compared to samples dominated by coarser size classes; however, samples from sandbar complex A that had the API 40/70 size class tested also had a higher rate for meeting the minimum criterion (57 percent) than did samples from sandbar complexes B, C, and D (50, 43, and 40 percent, respectively). For samples collected along the lower Niobrara River, of the 25 tested samples of 40/70-sized sand, 9 samples passed the API minimum criterion at 34.5 MPa, but only 3 samples passed the more-stringent criterion of 8 percent postcrush fines. All four tested samples of 70/140 sand passed the minimum criterion at 34.5 MPa, with postcrush fines percentage of at most 4.1 percent.For two reaches of the lower Niobrara River, where hydraulic sorting was energized artificially by the hydraulic head drop at and immediately downstream from Spencer Dam, suitability of channel deposits for potential use as fracture sand was confirmed by test results. All reach A washed samples were well-rounded and had sphericity scores above 0.65, and samples for 80 percent of sampled locations met the crush-resistance criterion at the 34.5-MPa stress level. A conservative lower-bound estimate of sand volume in the reach A deposits was about 86,000 cubic meters. All reach B samples were well-rounded but sphericity averaged 0.63, a little less than the average for upstream reaches A and SP. All four samples tested passed the crush-resistance test at 34.5 MPa. Of three reach B sandbars, two had no more than 3 percent fines after the crush test, surpassing more stringent criteria for crush resistance that accept a maximum of 6 percent fines following the crush test for the API 70/140 size class.Relative to the crush-resistance test results for the API 40/70 size fraction of two samples of mine output from Loup River settling-basin dredge spoils near Genoa, Nebr., four of five reach A sample locations compared favorably. The four samples had increases in fines composition of 1.6–5.9 percentage points, whereas fines in the two mine-output samples increased by an average 6.8 percentage points.

Oscar Renda Contracting Inc. Navajo Nation Crushing/Screening Operation: Coverage Under General Air Quality Permit for Stone Quarrying, Crushing and Screening Facilities

EPA Pesticide Factsheets

Documents related to approved request for coverage under the Stone Quarrying, Crushing and Screening Facilities General Permit for Oscar Renda Contracting Inc. Navajo Nation Crushing/Screening Operation located in McKinley and San Juan Counties, NM.

Possible role of antioxidative capacity of (-)-epigallocatechin-3-gallate treatment in morphological and neurobehavioral recovery after sciatic nerve crush injury.

PubMed

Renno, Waleed M; Benov, Ludmil; Khan, Khalid M

2017-11-01

OBJECTIVE This study examined the capacity of the major polyphenolic green tea extract (-)-epigallocatechin-3-gallate (EGCG) to suppress oxidative stress and stimulate the recovery and prompt the regeneration of sciatic nerve after crush injury. METHODS Adult male Wistar rats were randomly assigned to one of 4 groups: 1) Naïve, 2) Sham (sham injury, surgical control group), 3) Crush (sciatic nerve crush injury treated with saline), and 4) Crush+EGCG (sciatic nerve crush injury treated with intraperitoneally administered EGCG, 50 mg/kg). All animals were tested for motor and sensory neurobehavioral parameters throughout the study. Sciatic nerve and spinal cord tissues were harvested and processed for morphometric and stereological analysis. For the biochemical assays, the time points were Day 1, Day 7, Day 14, and Day 28 after nerve injury. RESULTS After sciatic nerve crush injury, the EGCG-treated animals (Crush+EGCG group) showed significantly better recovery of foot position and toe spread and 50% greater improvement in motor recovery than the saline-treated animals (Crush group). The Crush+EGCG group displayed an early hopping response at the beginning of the 3rd week postinjury. Animals in the Crush+EGCG group also showed a significant reduction in mechanical allodynia and hyperalgesia latencies and significant improvement in recovery from nociception deficits in both heat withdrawal and tail flick withdrawal latencies compared with the Crush group. In both the Crush+EGCG and Crush groups, quantitative evaluation revealed significant morphological evidence of neuroregeneration according to the following parameters: mean cross-sectional area of axons, myelin thickness in the sciatic nerve (from Week 4 to Week 8), increase of myelin basic protein concentration and gene expression in both the injured sciatic nerve and spinal cord, and fiber diameter to axon diameter ratio and myelin thickness to axon diameter ratio at Week 2 after sciatic nerve injury. However, the axon area remained much smaller in both the Crush+EGCG and Crush groups compared with the Sham and Naïve groups. The number of axons per unit area was significantly decreased in the Crush+EGCG and Crush groups compared with controls. Sciatic nerve injury produced generalized oxidative stress manifested as a significant increase of isoprostanes in the urine and decrease of the total antioxidant capacity (TAC) of the blood from Day 7 until Day 14. EGCG-treated rats showed significantly less increase of isoprostanes than saline-treated animals and also showed full recovery of TAC levels by Day 14 after nerve injury. In spinal cord tissue analysis, EGCG-treated animals showed induced glutathione reductase and suppressed induction of heme oxygenase 1 gene expression compared with nontreated animals. CONCLUSIONS EGCG treatment suppressed the crush-induced production of isoprostanes and stimulated the recovery of the TAC and was associated with remarkable alleviation of motor and sensory impairment and significant histomorphological evidence of neuronal regeneration following sciatic nerve crush injury in rats. The findings of this study suggest that EGCG can be used as an adjunctive therapeutic remedy for nerve injury. However, further investigations are needed to establish the antioxidative mechanism involved in the regenerative process after nerve injury. Only upregulation of glutathione reductase supports the idea that EGCG is acting indirectly via induction of enzymes or transcription factors.

Optimum reaction ratio of coal fly ash to blast furnace cement for effective removal of hydrogen sulfide.

PubMed

Asaoka, Satoshi; Okamura, Hideo; Kim, Kyunghoi; Hatanaka, Yuzuru; Nakamoto, Kenji; Hino, Kazutoshi; Oikawa, Takahito; Hayakawa, Shinjiro; Okuda, Tetsuji

2017-02-01

Reducing hydrogen sulfide concentration in eutrophic marine sediments is crucial to maintaining healthy aquatic ecosystems. Managing fly ash, 750 million tons of which is generated annually throughout the world, is another serious environmental problem. In this study, we develop an approach that addresses both these issues by mixing coal fly ash from coal-fired power plants with blast furnace cement to remediate eutrophic sediments. The purpose of this study is to optimize the mixing ratio of coal fly ash and blast furnace cement to improve the rate of hydrogen sulfide removal based on scientific evidence obtained by removal experiments and XAFS, XRD, BET, and SEM images. In the case of 10 mg-S L -1 of hydrogen sulfide, the highest removal rate of hydrogen sulfide was observed for 87 wt% of coal fly ash due to decreased competition of adsorption between sulfide and hydroxyl ions. Whereas regarding 100 mg-S L -1 , the hydrogen sulfide removal rate was the highest for 95 wt% of coal fly ash. However, for both concentrations, the removal rate obtained by 87 wt% and 95 wt% were statistically insignificant. The crushing strength of the mixture was over 1.2 N mm -2 when the coal fly ash mixing ratio was less than 95 wt%. Consequently, the mixing ratio of coal fly ash was optimized at 87 wt% in terms of achieving both high hydrogen sulfide removal rate and sufficient crushing strength. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance.

PubMed

Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol ® ATO 5/Transcutol ® HP and tallow fat/Transcutol ® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol ® ATO 5/Transcutol ® HP batch, then 81% and 95% for tallow fat/Transcutol ® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol ® ATO 5/Transcutol ® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol ® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem ® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference ( P <0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms.

Sustained-release liquisolid compact tablets containing artemether–lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

PubMed Central

Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

2016-01-01

The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (P<0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. PMID:27932882

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation.

PubMed

Vanhoorne, V; Bekaert, B; Peeters, E; De Beer, T; Remon, J-P; Vervaet, C

2016-06-15

In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400-900rpm), granulation temperature (25-40°C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma™-25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ- to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, less-soluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different. Copyright © 2016 Elsevier B.V. All rights reserved.

Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

PubMed

Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

2017-08-08

Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had acute liver injury subsequently which gradually improved with supportive care. Her liver functions found to be completely normal 1 week after the discharge. Poisoning with fixed drug combination of isoniazid and rifampicin tablets is rare but can cause severe morbidity and mortality if not treated promptly. Oral pyridoxine can substitute for intravenous pyridoxine with almost similar efficacy at a low cost in managing patients with acute severe standard isoniazid poisoning in resource poor setting.

Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions.

PubMed

Colucci, Philippe; D'Angelo, Pina; Mautone, Giuseppe; Scarsi, Claudia; Ducharme, Murray P

2011-06-01

To assess the pharmacokinetic equivalence of a new soft capsule formulation of levothyroxine versus a marketed reference product and to assess the soft capsule formulated with stricter potency guidelines versus the capsule before the implementation of the new potency rule. Two single-dose randomized two-way crossover pharmacokinetic equivalence studies and one dosage form proportionality single-dose study comparing low, medium, and high strengths of the new formulation. All three studies were performed in a clinical setting. Participants were healthy male and female adult subjects with normal levothyroxine levels. A total of 90 subjects participated in the three studies. Pharmacokinetic parameters were calculated on baseline- adjusted concentrations. The first pharmacokinetic equivalence study compared the levothyroxine sodium soft capsule formulation (Tirosint) with the reference Synthroid tablets and the two products were considered bioequivalent. The dosage form proportionality study compared the 50-, 100-, and 150-μg test capsules strengths dosed at the same level (600 μg) and all three strengths were considered equivalent when given at the same dosage. The last study compared the test capsule used in the first two studies with a new capsule formulation following the new potency guideline (±5%) set forward by the Food and Drug Administration and the two capsules were considered bioequivalent. Doses were well tolerated by subjects in all three studies with no serious adverse events reported. The levothyroxine soft capsule formulated with the stricter new potency guideline set forward by the Food and Drug Administration met equivalence criteria in terms of rate and extent of exposure under fasting conditions to the reference tablet formulation. Clinical doses of the capsule formulation can be given using any combination of the commercialized strengths.

21 CFR 137.195 - Crushed wheat.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Crushed wheat. 137.195 Section 137.195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Related Products § 137.195 Crushed wheat. Crushed wheat, coarse ground wheat, is the food prepared by so...

Formulation and Evaluation of Fast-Disintegrating Sublingual Tablets of Atropine Sulfate: the Effect of Tablet Dimensions and Drug Load on Tablet Characteristics.

PubMed

Aodah, Alhussain; Bafail, Rawan S; Rawas-Qalaji, Mutasem

2017-07-01

In this study, we formulated and evaluated the effects of tablet dimensions and drug load on the characteristics of atropine sulfate (AS) fast-disintegrating sublingual tablets (FDSTs). We aim to develop AS FDSTs as an alternative non-invasive and portable dosage form for the emergency treatment of organophosphate (OP) toxicity. AS autoinjector, AtroPen®, is the only self-administered dosage form available as an antidote for-out-of-hospital emergency use, but it is associated with several limitations and drawbacks. Seven FDST formulations of two tablet sizes, 150 mg (A) and 50 mg (B), and of several AS loads, 0 mg (A1, B1), 2 mg (A2, B2), 4 mg (B3), and 8 mg (B4a, B4b), were formulated and manufactured by direct compression. AS FDST characteristics were evaluated using USP and non-USP tests. Results were statistically compared at p < 0.05. All FDSTs passed the USP content uniformity and friability tests, disintegrated and released AS in ≤30 and 60 s. B1 and B2 were significantly harder than A1 and A2. Water uptake of A1 was significantly the highest. However, B1 and B2 had shorter disintegration and wetting times and higher amounts of AS dissolved than did A1 and A2 (p < 0.05). Increasing AS negatively affected FDST tensile strength (p < 0.05 for B4a) and water uptake (p < 0.05 for B3, B4a and B4b), however, without affecting AS dissolution. Formulation of AS up to 16% into smaller FDSTs was successful. Smaller FDSTs were harder and disintegrated more quickly. These AS FDSTS have the potential for further in vivo testing to evaluate their OP antidote potential.

Crushed Cartilage: A Rescue Procedure in Rhinoplasty.

PubMed

Boccieri, Armando; Marianetti, Tito M; Pascali, Michele

2018-05-01

While the use of crushed cartilage is now universally recognized as a valid procedure in rhinoplasty to mask irregularities and eliminate slight deficits, there is still no consensus as to the optimal degree of crushing and the rate of graft resorption over time. With a view to casting light on these 2 important aspects and providing some guidelines, the authors present a study of 123 patients subjected to grafts of cartilage with different degrees of crushing in the different areas of the nasal pyramid: upper third (45 patients), middle third (40), and lower third (38). The degree of crushing was medium for 95 patients and high for 28 who presented thinner and less elastic skin. Comparison of the performance over time of the cartilage grafts inserted in the same areas but with different degrees of crushing provides important indications as regard the best way of preparing the material. The results proved satisfactory with improvements for all of the 95 patients subjected to grafts of moderately crushed cartilage. The initial defect was instead still present, albeit with some partial improvement, at a distance of 12 months in 17 of the 28 patients where highly crushed cartilage was used. The study suggests that a moderate degree of crushing offers better results as regard flexibility and stability over time.

Characteristics of Crushing Energy and Fractal of Magnetite Ore under Uniaxial Compression

NASA Astrophysics Data System (ADS)

Gao, F.; Gan, D. Q.; Zhang, Y. B.

2018-03-01

The crushing mechanism of magnetite ore is a critical theoretical problem on the controlling of energy dissipation and machine crushing quality in ore material processing. Uniaxial crushing tests were carried out to research the deformation mechanism and the laws of the energy evolution, based on which the crushing mechanism of magnetite ore was explored. The compaction stage and plasticity and damage stage are two main compression deformation stages, the main transitional forms from inner damage to fracture are plastic deformation and stick-slip. In the process of crushing, plasticity and damage stage is the key link on energy absorption for that the specimen tends to saturate energy state approaching to the peak stress. The characteristics of specimen deformation and energy dissipation can synthetically reply the state of existed defects inner raw magnetite ore and the damage process during loading period. The fast releasing of elastic energy and the work done by the press machine commonly make raw magnetite ore thoroughly broken after peak stress. Magnetite ore fragments have statistical self-similarity and size threshold of fractal characteristics under uniaxial squeezing crushing. The larger ratio of releasable elastic energy and dissipation energy and the faster energy change rate is the better fractal properties and crushing quality magnetite ore has under uniaxial crushing.

Effect of warning symbols in combination with education on the frequency of erroneously crushing medication in nursing homes: an uncontrolled before and after study

PubMed Central

van Welie, Steven; Wijma, Linda; Beerden, Tim; van Doormaal, Jasperien; Taxis, Katja

2016-01-01

Objectives Residents of nursing homes often have difficulty swallowing (dysphagia), which complicates the administration of solid oral dosage formulations. Erroneously crushing medication is common, but few interventions have been tested to improve medication safety. Therefore, we evaluated the effect of warning symbols in combination with education on the frequency of erroneously crushing medication in nursing homes. Setting This was a prospective uncontrolled intervention study with a preintervention and postintervention measurement. The study was conducted on 18 wards (total of 200 beds) in 3 nursing homes in the North of the Netherlands. Participants We observed 36 nurses/nursing assistants (92% female; 92% nursing assistants) administering medication to 197 patients (62.9% female; mean age 81.6). Intervention The intervention consisted of a set of warning symbols printed on each patient's unit dose packaging indicating whether or not a medication could be crushed as well as education of ward staff (lectures, newsletter and poster). Primary outcome measure The relative risk (RR) of a crushing error occurring in the postintervention period compared to the preintervention period. A crushing error was defined as the crushing of a medication considered unsuitable to be crushed based on standard reference sources. Data were collected using direct (disguised) observation of nurses during drug administration. Results The crushing error rate decreased from 3.1% (21 wrongly crushed medicines out of 681 administrations) to 0.5% (3/636), RR=0.15 (95% CI 0.05 to 0.51). Likewise, there was a significant reduction using data from patients with swallowing difficulties only, 87.5% (21 errors/24 medications) to 30.0% (3/10) (RR 0.34, 95% CI 0.13 to 0.89). Medications which were erroneously crushed included enteric-coated formulations (eg, omeprazole), medication with regulated release systems (eg, Persantin; dipyridamol) and toxic substances (eg, finasteride). Conclusions Warning symbols combined with education reduced erroneous crushing of medication, a well-known and common problem in nursing homes. PMID:27496242

Are age-appropriate antibiotic formulations missing from the WHO list of essential medicines for children? A comparison study.

PubMed

Ivanovska, Verica; Leufkens, Hubert G; Rademaker, Carin Ma; Zisovska, Elizabeta; Pijnenburg, Mariëlle W; van Dijk, Liset; Mantel-Teeuwisse, Aukje K

2017-04-01

There is a global call for formulations, which are better suited for children of different age categories and in a variety of settings. One key public health area of interest is age-appropriate paediatric antibiotics. We aimed to identify clinically relevant paediatric formulations of antibiotics listed on pertinent formularies that were not on the WHO Essential Medicines List for Children (EMLc). We compared four medicines lists versus the EMLc and contrasted paediatric antibiotic formulations in relation to administration routes, dosage forms and/or drug strengths. The additional formulations on comparator lists that differed from the EMLc formulations were evaluated for their added clinical values and costs. The analysis was based on 26 EMLc antibiotics. Seven oral and two parenteral formulations were considered clinically relevant for paediatric use. Frequently quoted benefits of oral formulations included: filling the gap of unmet therapeutic needs in certain age/weight groups (phenoxymethylpenicillin and metronidazole oral liquids, and nitrofurantoin capsules), and simplified administration and supply advantages (amoxicillin dispersible tablets, clyndamycin capsules, cloxacillin tablets, and sulfamethoxazole+trimethoprim tablets). Lower doses of ampicillin and cefazolin powder for injection could simplify the dosing in newborns and infants, reduce the risk of medical errors, and decrease the waste of medicines, but may target only narrow age/weight groups. The identified additional formulations of paediatric antibiotics on comparator lists may offer clinical benefits for low-resource settings, including simplified administration and increased dosing accuracy. The complexity of both procuring and managing multiple strengths and formulations also needs to be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters.

PubMed

Vanhoorne, V; Vanbillemont, B; Vercruysse, J; De Leersnyder, F; Gomes, P; Beer, T De; Remon, J P; Vervaet, C

2016-05-30

The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fines were present. Temperature was also an important parameter to optimize as a higher temperature yielded less fines and positively influenced the aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable to that of immediate release formulations. Tensile strength and friability of tablets were not dependent on the process parameters. The use of starch as filler was not beneficial with regard to granule and tablet properties. Complete drug release was obtained after 16-20h and was independent of the design's parameters. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis of Thiolated Alginate and Evaluation of Mucoadhesiveness, Cytotoxicity and Release Retardant Properties

PubMed Central

Jindal, A. B.; Wasnik, M. N.; Nair, Hema A.

2010-01-01

Modification of polymers by covalent attachment of thiol bearing pendant groups is reported to impart many beneficial properties to them. Hence in the present study, sodium alginate–cysteine conjugate was synthesized by carbodiimide mediated coupling under varying reaction conditions and the derivatives characterized for thiol content. The thiolated alginate species synthesized had bound thiol content ranging from 247.8±11.03–324.54±10.107 ΅mol/g of polymer depending on the reaction conditions. Matrix tablets based on sodium alginate-cysteine conjugate and native sodium alginate containing tramadol hydrochloride as a model drug were prepared and mucoadhesive strength and in vitro drug release from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of the drug was released within 1 h from corresponding tablets prepared using native sodium alginate. An approximately 2-fold increase in the minimal detachment force of the tablets from an artificial mucin film was observed for sodium alginate–cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that at low concentrations of polymer, sodium alginate–cysteine conjugate was less toxic to L-929 mouse fibroblast cell line when compared to native sodium alginate. Hence, thiolation is found to be a simple route to improving polymer performance. The combination of improved controlled drug release and mucoadhesive properties coupled with the low toxicity of these new excipients builds up immense scope for the use of thiolated polymers in mucoadhesive drug delivery systems. PMID:21969750

Development of Oral Flexible Tablet (OFT) Formulation for Pediatric and Geriatric Patients: a Novel Age-Appropriate Formulation Platform.

PubMed

Chandrasekaran, Prabagaran; Kandasamy, Ruckmani

2017-08-01

Development of palatable formulations for pediatric and geriatric patients involves various challenges. However, an innovative development with beneficial characteristics of marketed formulations in a single formulation platform was attempted. The goal of this research was to develop solid oral flexible tablets (OFTs) as a platform for pediatrics and geriatrics as oral delivery is the most convenient and widely used mode of drug administration. For this purpose, a flexible tablet formulation using cetirizine hydrochloride as model stability labile class 1 and 3 drug as per the Biopharmaceutical Classification System was developed. Betadex, Eudragit E100, and polacrilex resin were evaluated as taste masking agents. Development work focused on excipient selection, formulation processing, characterization methods, stability, and palatability testing. Formulation with a cetirizine-to-polacrilex ratio of 1:2 to 1:3 showed robust physical strength with friability of 0.1% (w/w), rapid in vitro dispersion within 30 s in 2-6 ml of water, and 0.2% of total organic and elemental impurities. Polacrilex resin formulation shows immediate drug release within 30 min in gastric media, better taste masking, and acceptable stability. Hence, it is concluded that ion exchange resins can be appropriately used to develop taste-masked, rapidly dispersible, and stable tablet formulations with tailored drug release suitable for pediatrics and geriatrics. Flexible formulations can be consumed as swallowable, orally disintegrating, chewable, and as dispersible tablets. Flexibility in dose administration would improve compliance in pediatrics and geriatrics. This drug development approach using ion exchange resins can be a platform for formulating solid oral flexible drug products with low to medium doses.

Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

PubMed

Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-25

Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation-induced errors in EPR dosimetry of enamel: pre- and post-crushing sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haskell, E.H.; Hayes, R.B.; Kenner, G.H.

1996-01-01

Errors in dose estimation as a function of grain size for tooth enamel has been previously shown for beta irradiation after crushing. We tested the effect of gamma radiation applied to specimens before and after crushing. We extend the previous work in that we found that post-crushing irradiation altered the slope of the dose-response curve of the hydroxyapatite signal and produced a grain-size dependent offset. No changes in the slope of the dose-response curve were seen in enamel caps irradiated before crushing.

Frictional behavior and BET surface-area changes of SAFOD gouge at intermediate to seismic slip rates

NASA Astrophysics Data System (ADS)

Sawai, Michiyo; Shimamoto, Toshihiko; Mitchell, Thomas; Kitajima, Hiroko; Hirose, Takehiro

2013-04-01

The San Andreas Fault Observatory at Depth (SAFOD) Drilling site is located near the southern end of the creeping section of the San Andreas fault. Experimental studies on the frictional properties of fault gouge from SAFOD drill cores may provide valuable information on the cause of diverse fault motion. We conducted friction experiments on gouge from the southwest deformation zone (SDZ, Phase III core; Hole G-Run 2-Section 8) where creep is confirmed by ongoing borehole casing deformation, at intermediate to high slip rates (10-5 to 1.3 m/s), at a normal stress of about 1 MPa, and under both dry (room humidity) and wet (25 wt% of H2O added, drained tests) conditions. Experiments were performed with two rotary-shear friction apparatuses. One gram of gouge was placed between specimens of Belfast gabbro 25 mm in diameter surrounded by a Teflon sleeve to confine the gouge. Slip rate was first decreased and then increased in a step-wise manner to obtain the steady-state friction at intermediate slip rates. The friction coefficient increases from about 0.13 to 0.37 as the slip rate increases from 0.8 x 10-5 to 9.7 x 10-3 m/s. Our results agree with frictional strength measured at higher effective normal stress (100 MPa) by the Brown University group in the same material. Data shows pronounced velocity strengthening at intermediate slip rates, which is unfavorable for rupture nucleation and may be a reason for having creep behavior. On the other hand, the steady-state friction markedly decreases at high velocity, and such weakening may allow earthquake rupture to propagate into the creeping section, once the intermediate strength barrier is overcome. Gouge temperature, measured at the edge of the stationary sample during seismic fault motion, increased to around 175oC under dry conditions, but increased up to 100oC under wet conditions. We measured BET surface area of gouge before and after deformation to determine the energy used for grain crushing. The initial specific surface area (2.6-3.4 m2/g) increases to 14-24 m2/g for dry gouge deformed at intermediate slip rates and to 45-60 m2/g for wet gouge deformed at subseismic to seismic slip rates. The results suggest that approximately 2 % and less than 1 % of the frictional work is absorbed in grain crushing for dry and wet gouges, respectively, if the fracture surface energy of muscovite (0.38 J/m2) is used as the surface energy of phyllosilicate-rich SAFOD gouge. Thus grain crushing cannot be an important energy sink during seismic fault motion. The surface area tends to be lower for gouge deformed at high slip rates for both dry and wet gouges. This results and SEM observations of gouge strongly suggests that welding of grains takes place at high slip rate due to frictional heating and counteracts the surface-area increase due to grain crushing. Thus intrafault processes are more complex than in a simple scenario of "grain crushing and surface-area increase" assumed in recent studies. Surface area is greater for wet gouge than for dry gouge suggesting that pore water separating gouge particles suppresses grain welding.

Modeling Composite Laminate Crushing for Crash Analysis

NASA Technical Reports Server (NTRS)

Fleming, David C.; Jones, Lisa (Technical Monitor)

2002-01-01

Crash modeling of composite structures remains limited in application and has not been effectively demonstrated as a predictive tool. While the global response of composite structures may be well modeled, when composite structures act as energy-absorbing members through direct laminate crushing the modeling accuracy is greatly reduced. The most efficient composite energy absorbing structures, in terms of energy absorbed per unit mass, are those that absorb energy through a complex progressive crushing response in which fiber and matrix fractures on a small scale dominate the behavior. Such failure modes simultaneously include delamination of plies, failure of the matrix to produce fiber bundles, and subsequent failure of fiber bundles either in bending or in shear. In addition, the response may include the significant action of friction, both internally (between delaminated plies or fiber bundles) or externally (between the laminate and the crushing surface). A figure shows the crushing damage observed in a fiberglass composite tube specimen, illustrating the complexity of the response. To achieve a finite element model of such complex behavior is an extremely challenging problem. A practical crushing model based on detailed modeling of the physical mechanisms of crushing behavior is not expected in the foreseeable future. The present research describes attempts to model composite crushing behavior using a novel hybrid modeling procedure. Experimental testing is done is support of the modeling efforts, and a test specimen is developed to provide data for validating laminate crushing models.

Evaluating the Psychological Concomitants of Other-Sex Crush Experiences during Early Adolescence

PubMed Central

Bowker, Julie C.; Etkin, Rebecca G.

2016-01-01

Very little empirical attention has been paid to other-sex crush experiences during adolescence. As a result, it is not known whether such experiences, which appear to be relatively common, impact psychological adjustment outcomes. This two-wave (3 month interval) longitudinal study of 268 young adolescents (48% girls; M age at Time 1 = 11.84 years) examined the psychological concomitants of other-sex crush experiences (having and being viewed by others as a crush). Anxious-withdrawal and gender were evaluated as moderators. Peer nomination measures at Time 1 assessed both types of crush experiences and mutual friendship involvement, and participants completed self-report measures of loneliness and depressive symptoms at Times 1 and 2. The results from regression analyses revealed significant associations between having an other-sex crush and depressive symptoms at Time 1, after accounting for the effects of mutual friendship. Two interaction effects also revealed that crush status was a risk factor for depressive symptoms at low levels of anxious-withdrawal but a protective factor at high levels. The findings provide the first empirical evidence that other-sex crush experiences are developmentally significant during early adolescence. PMID:26984754

Preconditioning crush increases the survival rate of motor neurons after spinal root avulsion

PubMed Central

Li, Lin; Zuo, Yizhi; He, Jianwen

2014-01-01

In a previous study, heat shock protein 27 was persistently upregulated in ventral motor neurons following nerve root avulsion or crush. Here, we examined whether the upregulation of heat shock protein 27 would increase the survival rate of motor neurons. Rats were divided into two groups: an avulsion-only group (avulsion of the L4 lumbar nerve root only) and a crush-avulsion group (the L4 lumbar nerve root was crushed 1 week prior to the avulsion). Immunofluorescent staining revealed that the survival rate of motor neurons was significantly greater in the crush-avulsion group than in the avulsion-only group, and this difference remained for at least 5 weeks after avulsion. The higher neuronal survival rate may be explained by the upregulation of heat shock protein 27 expression in motor neurons in the crush-avulsion group. Furthermore, preconditioning crush greatly attenuated the expression of nitric oxide synthase in the motor neurons. Our findings indicate that the neuroprotective action of preconditioning crush is mediated through the upregulation of heat shock protein 27 expression and the attenuation of neuronal nitric oxide synthase upregulation following avulsion. PMID:25206852

Airborne particles released by crushing CNT composites

NASA Astrophysics Data System (ADS)

Ogura, I.; Okayama, C.; Kotake, M.; Ata, S.; Matsui, Y.; Gotoh, K.

2017-06-01

We investigated airborne particles released as a result of crushing carbon nanotube (CNT) composites using a laboratory scale crusher with rotor blades. For each crushing test, five pellets (approximately 0.1 g) of a polymer (polystyrene, polyamide, or polycarbonate) containing multiwall CNTs (Nanocyl NC7000 or CNano Flotube9000) or no CNTs were placed in the container of the crusher. The airborne particles released by the crushing of the samples were measured. The real-time aerosol measurements showed increases in the concentration of nanometer- and micrometer-sized particles, regardless of the sample type, even when CNT-free polymers were crushed. The masses of the airborne particles collected on filters were below the detection limit, which indicated that the mass ratios of the airborne particles to the crushed pellets were lower than 0.02%. In the electron microscopic analysis, particles with protruding CNTs were observed. However, free-standing CNTs were not found, except for a poorly dispersed CNT-polystyrene composite. This study demonstrated that the crushing test using a laboratory scale crusher is capable of evaluating the potential release of CNTs as a result of crushing CNT composites. The advantage of this method is that only a small amount of sample (several pieces of pellets) is required.

Stability of pyrimethamine in a liquid dosage formulation stored for three months.

PubMed

Nahata, M C; Morosco, R S; Hipple, T F

1997-12-01

The stability of pyrimethamine in a liquid dosage formulation stored for up to three months was studies. Commercially available 25-mg pyrimethamine tablets were crushed with a mortar and pestle and mixed with a 1:1 mixture of Simple Syrup, NF, and 1% methylcellulose to yield a suspension with a pyrimethamine concentration of 2 mg/mL. The suspension was poured into 10 amber plastic and 10 amber glass prescription bottles; 5 plastic and 5 glass bottles were stored at 4 degrees C, and the remaining bottles were kept at 25 degrees C. Samples were collected at intervals up to 91 days and tested for pyrimethamine concentration by stability-indicating high-performance liquid chromatography. Pyrimethamine remained stable throughout the three-month study period under all conditions. At 4 degrees C, pyrimethamine concentrations remained above 96% of the initial concentration; at 25 degrees C, pyrimethamine concentrations remained above 91%. No substantial changes in pH were observed. Pyrimethamine was stable for at least 91 days in an oral suspension stored in plastic or glass prescription bottles at 4 or 25 degrees C.

Moisture plasticization for enteric Eudragit® L30D-55-coated pellets prior to compression into tablets.

PubMed

Rujivipat, Soravoot; Bodmeier, Roland

2012-05-01

Enteric polymers such as cellulose esters (cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate) and methacrylic acid-acrylate copolymers (Eudragit® L100-55 and S100) are quite brittle in the dry state and thus not suitable as pellet coatings for compression into tablets. The objective of this study was to investigate the role of humidity treatment for moisture plasticization in order to successfully compress the enterically coated pellets. The mechanical properties of Eudragit® L100-55 improved dramatically, while the properties of the other enteric polymers showed only minor changes after storage at higher humidity. The significant increase in flexibility of the Eudragit® L film was caused by hydration/plasticization; its elongation value changed from approx. 3% in the dry state to approx. 140% at the higher storage humidity. Storage at 84% relative humidity resulted in comparable release profiles of compressed and uncompressed pellets. The glass transition temperature of Eudragit® L films decreased below the compression temperature (room temperature) at storage humidities between 75% and 84%. The glass transition relative humidity leading to a change from the glassy to the rubbery state was determined by dynamic vapor sorption (DVS) to be 76.8%. Moisture resulted in superior plasticization for Eudragit® L than the conventional plasticizer triethyl citrate. The improved compressibility of high humidity treated Eudragit® L-coated pellets was also shown with single pellet compression data as indicated by an increased crushing force and deformation. In conclusion, moisture plasticization was a highly effective tool to enable the successful compression of pellets coated with the brittle enteric polymer Eudragit® L. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

PubMed

Gandolf, A Rae; Papich, Mark G; Bringardner, Amy B; Atkinson, Mark W

2005-05-01

To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. 6 adult female alpacas. A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

Stability of an extemporaneously prepared alcohol-free phenobarbital suspension.

PubMed

Cober, Mary Petrea; Johnson, Cary E

2007-03-15

The physical and chemical short-term stability of alcohol-free, oral suspensions of phenobarbital 10 mg/mL prepared from commercially available tablets in both a sugar and a sugar-free vehicle was assessed at room temperature. Phenobarbital oral suspension 10 mg/mL was prepared by crushing 10 60-mg tablets of phenobarbital with a mortar and pestle. A small amount of Ora-Plus was added to the phenobarbital powder to sufficiently wet the particles. A 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF was combined with the phenobarbital powder to produce a final volume of 60 mL. Three identical samples of each of the two different formulations were prepared and stored at room temperature in 2-oz amber plastic bottles. Immediately after preparation and at 15, 30, 60, and 115 days, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography. The samples were tasted and inspected for color and odor changes. The percent of the initial concentration remaining at each study time for each phenobarbital suspension was determined. Stability was defined as the retention of at least 90% of the initial concentration. There were no detectable changes in color, odor, and taste and no visible microbial growth in any sample. At least 98% of the initial phenobarbital concentration remained throughout the 115-day study period in both preparations. An extemporaneously prepared alcohol-free suspension of phenobarbital 10 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF was stable for at least 115 days when stored in 2-oz amber plastic bottles at room temperature.

Use of ferric chloride to identify salicylate-containing poisons.

PubMed

Hoffman, Robert J; Nelson, Lewis S; Hoffman, Robert S

2002-01-01

Ferric chloride (FeCl3) is used to qualitatively test the urine of patients with presumed salicylate exposure. FeCl3 testing of an unidentified poison might provide evidence of salicylate exposure in situations where FeCl3 urine testing cannot be used. Such situations include the absence of a urine sample, immediately after ingestion before urine contains a detectable quantity of salicylate, or for patients chronically using salicylatesfor which FeCl3 testing is unhelpful. This study seeks to determine if FeCl3 can be used to identify salicylate-containing products. We assessed the reactivity of FeCl3 with commercially available salicylate-containing products. We applied 0.1 mL of 10% FeCl3 solution to each of 15 various salicylate-containing products including: regular and buffered acetylsalicylic acid, bismuth subsalicylate, methylsalicylate, physostigmine salicylate, salicylic acid, trolamine salicylate, and herbal tablets with salicin-containing white willow bark (Salix sp.). These products tested were: regular and enteric-coatedpills (n = 4), powder (n = 1), topical creams (n = 5), topical liquids (n = 4), and intravenous solution (n = 1). FeCl3 was applied to crushed tablets and added directly to liquids and creams. Fifteen salicylate-free controls including liquids, pills, and creams similar in appearance to experimental samples were also tested. Three blinded physiciansfamiliar with FeCl3 testing independently observed the addition of FeCl3 to each sample and rated a positive or negative result. All salicylate-containing products were interpreted to be clearly FeCl3 positive and all control samples were interpreted to be clearly FeCl3 negative. Salicylate-containing products may be identified using FeCl33. When using FeCl3

Modelling and analysis of the crush zone of a typical Australian passenger train

NASA Astrophysics Data System (ADS)

Sun, Y. Q.; Cole, C.; Dhanasekar, M.; Thambiratnam, D. P.

2012-07-01

In this paper, a three-dimensional nonlinear rigid body model has been developed for the investigation of the crashworthiness of a passenger train using the multibody dynamics approach. This model refers to a typical design of passenger cars and train constructs commonly used in Australia. The high-energy and low-energy crush zones of the cars and the train constructs are assumed and the data are explicitly provided in the paper. The crash scenario is limited to the train colliding on to a fixed barrier symmetrically. The simulations of a single car show that this initial design is only applicable for the crash speed of 35 km/h or lower. For higher speeds (e.g. 140 km/h), the crush lengths or crush forces or both the crush zone elements will have to be enlarged. It is generally better to increase the crush length than the crush force in order to retain the low levels of the longitudinal deceleration of the passenger cars.