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.

Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP.

PubMed

Ogunjimi, Abayomi Tolulope; Alebiowu, Gbenga

2014-04-01

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr's index, Hausner's ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength-friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.

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

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate for Respiratory Disorders

PubMed Central

Sharma, Deepak

2013-01-01

Recent developments in fast disintegrating tablets have brought convenience in dosing to pediatric and elderly patients who have trouble in swallowing tablets. The objective of the present study was to prepare the fast disintegrating tablet of salbutamol sulphate for respiratory disorders for pediatrics. As precision of dosing and patient's compliance become important prerequisites for a long-term treatment, there is a need to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling, and patient's acceptability. Hence, the present investigation were undertaken with a view to develop a fast disintegrating tablet of salbutamol sulphate which offers a new range of products having desired characteristics and intended benefits. Superdisintegrants such as sodium starch glycolate was optimized. Different binders were optimized along with optimized superdisintegrant concentration. The tablets were prepared by direct compression technique. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and uniformity of content. Optimized formulation was evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. It was concluded that fast disintegrating tablets of salbutamol sulphate were formulated successfully with desired characteristics which disintegrated rapidly; provided rapid onset of action; and enhanced the patient convenience and compliance. PMID:23956881

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.

Formulation and Evaluation of Mouth Disintegrating Tablets of Atenolol and Atorvastatin

PubMed Central

Sarfraz, R. M.; Khan, H. U.; Mahmood, A.; Ahmad, M.; Maheen, S.; Sher, M.

2015-01-01

In this study, mouth-disintegrating tablets of atenolol and atorvastatin combination were formulated using superdisintegrants to impart fast disintegration. Fifteen formulations were prepared based on different concentrations of two superdisintegrants, croscarmellose sodium and Kyron-T134. Three different techniques such as direct compression, effervescent and sublimation were used to study the effect of manufacturing processes, nature and concentration of superdisintegrants on various features of these tablets. Five formulations were made using each method. Precompression studies like bulk density, tapped density, angle of repose, Carr's compressibility index, Hausner's ratio and compatibility studies such as Fourier transform infrared spectroscopy and differential scanning calorimetry were performed. Various features such as hardness, thickness, diameter, weight variation, friability, disintegration time, dissolution studies, wetting time, wetting volume, water absorption ratio, modified disintegration, uniformity of contents and stability were evaluated. Finally results were statistically analyzed by the application of one way ANOVA test. Formulation F13 containing Kyron-T134 (6%) and croscarmellose sodium (2%) was found to be the best among all fifteen formulations prepared in all aspects evaluated. Sublimation method is found to be the best among three methods of preparation used. PMID:25767322

Isolation, characterization and investigation of Cordia dichotoma fruit polysaccharide as a herbal excipient.

PubMed

Pawar, Harshal Ashok; Jadhav, Pravin

2015-01-01

The objective of the present research work was to isolate, purify and characterize Cordia dichotoma gum and investigate its disintegration property in oral tablets. The isolated gum was tested for physicochemical characteristics such as solubility, pH (1% w/w in water), swelling index, loss on drying, ash value, bulk and tapped density, Carr's index, Hausner's ratio and angle of repose. The Orodispersible tablets of valsartan were prepared by direct compression method and evaluated for average weight (mg), drug content (%), thickness (mm), hardness (kg/cm(2)), friability (%), wetting time (sec), water absorption ratio (%) and disintegration time (sec). FTIR studies revealed that there was no interaction between drug, gum and other excipients used in the study. The F4 batch with disintegration time 26.34 ± 0.78 s and in vitro release 99.64 ± 0.43% was selected as optimized formulation. This formulation was compared with conventional marketed formulation and was found superior. Batch F4 was subjected to stability studies for three months and was tested for its disintegration time, drug contents and dissolution behaviour. Batch F4 was found stable for three months at accelerated temperature. Copyright © 2014 Elsevier B.V. All rights reserved.

Setting Ideal Lubricant Mixing Time for Manufacturing Tablets by Evaluating Powder Flowability.

PubMed

Nakamura, Shohei; Yamaguchi, Saori; Hiraide, Rikiha; Iga, Kumi; Sakamoto, Takatoshi; Yuasa, Hiroshi

2017-10-01

We investigated the effectiveness of using Carr's flowability index (FI) and practical angle of internal friction (Φ) as indexes for setting the target Mg-St mixing time needed for preparing tablets with the target physical properties. We used FI as a measure of flowability under non-loaded conditions, and Φ as a measure of flowability under loaded conditions for pharmaceutical powders undergoing direct compression with varying concentrations of Mg-St and mixing times. We evaluated the relationship between Mg-St mixing conditions and pharmaceutical powder flowability, analyzed the correlation between the physical properties of the tablets (i.e., tablet weight variation, drug content uniformity, hardness, friability, and disintegration time of tablets prepared using the pharmaceutical powder), and studied the effect of Mg-St mixing conditions and pharmaceutical powder flowability on tablet properties. Mg-St mixing time highly correlated with pharmaceutical powder FI (R 2  = 0.883) while Mg-St concentration has low correlation with FI, and FI highly correlated with the physical properties of the tablet (R 2 values: weight variation 0.509, drug content variation 0.314, hardness 0.525, friability 0.477, and disintegration time 0.346). Therefore, using pharmaceutical powder FI as an index could enable prediction of the physical properties of a tablet without the need for tableting, and setting the Mg-St mixing time by using pharmaceutical powder FI could enable preparation of tablets with the target physical properties. Thus, the FI of the intermediate product (i.e., pharmaceutical powder) is an effective index for controlling the physical properties of the finished tablet.

Orally disintegrating films: A modern expansion in drug delivery system.

PubMed

Irfan, Muhammad; Rabel, Sumeira; Bukhtar, Quratulain; Qadir, Muhammad Imran; Jabeen, Farhat; Khan, Ahmed

2016-09-01

Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs). These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API) within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

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.

Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

PubMed Central

El-Nabarawi, Mohamed A.; Tayel, Saadia A.; Soliman, Nadia A.; Abo Enin, Hadel A.

2013-01-01

Objective: A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety. Aim: The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH) as antihypertensive drug and buspirone hydrochloride (BuHCl) as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing. Materials and Methods: A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time) and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC) method. Bioavailability study of the selected formula study was carried out and followed by the clinical. Results: The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min). Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug's absorption. Conclusion: The results revealed that sublingual (F6) tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH can be attributed to the marked decline in DBP and SBP. That led to a reduction in the MAP. PMID:24082695

Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets

PubMed Central

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

2011-01-01

Aim: Orodispersible tablets also known as fast dissolving tablets disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate orodispersible tablets of nimesulide by using Lallemantia reylenne seeds as natural superdisintegrant. Materials and Methods: Powdered lallemantia seeds were characterized for powder flow properties (bulk density, tapped density, carr's consolidation index, hausner ratio, angle of repose), swelling index, viscosity, pH, and loss on drying. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in vitro dissolution and stability studies. Results and Discussion: Increase in Lallementia reylenne concentration had an appreciable effect on tablet hardness and friability which clearly indicated binding potential of the seeds. Water absorption ratio increased with increase in Lallemantia reylenne concentration from batch A1 to A4. Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Lallemantia reylenne seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. Conclusion: It could be concluded that Lallemantia reylenne seeds could be used as natural superdisintegrant in the formulation of orodispersible tablets. PMID:23071942

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

PubMed

Sadeghi, Mozhgan; Hemmati, Salar; Hamishehkar, Hamed

2016-01-01

Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, (1)H-NMR, and FTIR. PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

PubMed

Sadeghi, Mozhgan; Hemmati, Salar; Hamishehkar, Hamed

2016-05-01

Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, 1 H-NMR, and FTIR. PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

Valeriana officinalis Dry Plant Extract for Direct Compression: Preparation and Characterization.

PubMed

Gallo, Loreana; Ramírez-Rigo, María Veronica; Piña, Juliana; Palma, Santiago; Allemandi, Daniel; Bucalá, Verónica

2012-01-01

Valeriana officinalis L. (Valerianaceae) is one of the most widely used plants for the treatment of anxiety and insomnia. Usually dry plant extracts, including V. officinalis, are hygroscopic materials with poor physico-mechanical properties that can be directly compressed.A V. officinalis dry extract with moderate hygroscocity is suitable for direct compression, and was obtained by using a simple and economical technique. The V. officinalis fluid extract was oven-dried with colloidal silicon dioxide as a drying adjuvant. The addition of colloidal silicon dioxide resulted in a dry plant extract with good physico-mechanical properties for direct compression and lower hygroscopicity than the dry extract without the carrier. The dry plant extract glass transition temperature was considerably above room temperature (about 72 °C). The colloidal silicon dioxide also produced an antiplasticizing effect, improving the powder's physical stability.The pharmaceutical performance of the prepared V. officinalis dry extract was studied through the design of tablets. The manufactured tablets showed good compactability, friability, hardness, and disintegration time. Those containing a disintegrant (Avicel PH 101) exhibited the best pharmaceutical performance, having the lowest disintegration time of around 40 seconds.

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.

Development of standard operating procedures of Habbe Shifa: A polyherbal Unani formulation.

PubMed

Tarannum, Asira; Shamsi, Shariq; Zaman, Roohi

2013-07-01

Unani medicines are being used since antiquity. However, in spite of their efficacy, they have been widely criticized due to lack of standardization and poor quality presentation. For this reason, application of good manufacturing practices and development of standard operating procedures (SOPs) in the manufacture of herbal medicines became an essential tool to assure their quality. Therefore, the objective of the study was to develop the SOP of Habbe Shifa (HS) regarding the particle size (PS), binder, temperature of drying, and duration of drying. In this study, 24 batches of HS were prepared according to the instructions given in formulary to develop SOP. Three particle sizes (i.e., 80, 100, and 120 No. Mesh sieve), were taken for preparation of pills. Water and Samaghe Arabi (Gum Acacia mucilage [GAM]) were used as binder for preparing the lubdi (mass) in different batches. Different temperature and duration of drying were used to dry the pills in hot air oven to get satisfactory results. All the batches were assessed three times for hardness, friability, and disintegration time and mean regarded as standard parameter value. The batch with 150 μm PS (100 mesh sieve), 5% w/w GAM used as a binder, dried at 90°C for 120 min showed hardness 3.50 ± 0.00 kg/cm, friability 0.02 ± 0.003%, and disintegration time 25.00 ± 0.57 min, which showed most appropriate result among all batches and considered as final batch. Its SOP may be used for future reference which can help in setting up regulatory limit to assure the quality of Unani medicines.

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

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.

Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.

PubMed

El-Shenawy, Ahmed A; Ahmed, Mahmoud M; Mansour, Heba F; Abd El Rasoul, Saleh

2017-08-01

The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y 1 ), percentage friability (Y 2 ), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher C max and (AUC 0-12 ) and shorter T max than those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.

[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).

[Application of β-cyclodextrin in the formulation of ODT tablets containing ibuprofen].

PubMed

Zimmer, Łukasz; Kasperek, Regina; Poleszak, Ewa

2014-01-01

Oral disintegrating tablet (ODT) dissolves or disintegrates in saliva and then it is swallowed. Diluent in direct compression formulation has a dual role: it increases bulk of the dosage form and it promotes binding of the constituent particles of the formulation. Hence, selection of diluent is important in tablets produced by direct compression method. The aim of this work was to exame feasibility of preparing and optimizing oral disintegrating tablet formulation using β-cyclodextrin as a diluent. 400 mg round tablets were prepared by direct compression method on single punch tablet press using flat plain-face. 60% β-CD and MCC (microcrystalline cellulose - MCC-Vivapur 102) were used at different proportions for all the formulations. 5% of Kollidon CL was added as superdisintegrant. The eight formulations prepared were assessed for weight variation, thickness, disintegration time, hardness and dissolution rate according to FP IX. A dissolution test was performed at 37ºC using the paddle method at 50 rpm with 900 mL phosphate buffer (pH 6.8) as a dissolution medium. The content of ibuprofen sodium was found inside the ± 5% of the theoretical value. Hardness values of presented tablets were in the range 0.11-0.15 kG/mm2. Friability of the tablets lower than 1% indicates that the developed formulations can be processed and handled without excessive care. Disintegration time was in the range of 86 to 161 s. The results confirm the good mechanical properties of tablets containing β-CD. A composition with 20% β-CD and 40% MCC fulfilled a maximum requisite of an optimum formulation. These properties were similar to Ludiflash, the formulation used for comparison purposes. In the present study, higher concentration of β cyclodextrin was found to improve the hardness of tablets without increasing the disintegration time.

Valeriana officinalis Dry Plant Extract for Direct Compression: Preparation and Characterization

PubMed Central

Gallo, Loreana; Ramírez-Rigo, María Veronica; Piña, Juliana; Palma, Santiago; Allemandi, Daniel; Bucalá, Verónica

2012-01-01

Valeriana officinalis L. (Valerianaceae) is one of the most widely used plants for the treatment of anxiety and insomnia. Usually dry plant extracts, including V. officinalis, are hygroscopic materials with poor physico-mechanical properties that can be directly compressed. A V. officinalis dry extract with moderate hygroscocity is suitable for direct compression, and was obtained by using a simple and economical technique. The V. officinalis fluid extract was oven-dried with colloidal silicon dioxide as a drying adjuvant. The addition of colloidal silicon dioxide resulted in a dry plant extract with good physico-mechanical properties for direct compression and lower hygroscopicity than the dry extract without the carrier. The dry plant extract glass transition temperature was considerably above room temperature (about 72 °C). The colloidal silicon dioxide also produced an antiplasticizing effect, improving the powder’s physical stability. The pharmaceutical performance of the prepared V. officinalis dry extract was studied through the design of tablets. The manufactured tablets showed good compactability, friability, hardness, and disintegration time. Those containing a disintegrant (Avicel PH 101) exhibited the best pharmaceutical performance, having the lowest disintegration time of around 40 seconds. PMID:23264947

Ocimum Sanctum seeds, a natural superdisintegrant: formulation and evaluation of fast melt tablets of nimesulide.

PubMed

Malik, Karan; Arora, Gurpreet; Singh, Inderbir

2012-01-01

Fast melt tablets, also known as fast dissolving tablets, disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate fast melt tablets of nimesulide by using Ocimum Sanctum seeds as a natural tablet superdisintegrant. Powdered Ocimum seeds were characterized for powder flow properties (bulk density, tapped density, Carr's consolidation index, Hausner ratio, angle of repose), swelling index, viscosity, pH, loss on drying and microbial load. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in-vitro dissolution and stability studies. The swelling index was evaluated to be 1600. An appreciable effect of the natural material was seen on tablet hardness and friability. The water absorption ratio increased from 56.15 +/- 0.85 to 80.76 +/- 0.70 (A1-A4). Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Ocimum Sanctum seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. The f2 values (in comparison with Nimulid MD) of 95.90 and 93.65 were obtained with A3 and A4 batches respectively. It could be concluded that Ocimum Sanctum seeds could be used as a natural superdisintegrant in the formulation of fast melt tablets.

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.

Formulation studies for mirtazapine orally disintegrating tablets.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2016-01-01

Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

Design and optimization of disintegrating pellets of MCC by non-aqueous extrusion process using statistical tools.

PubMed

Gurram, Rajesh Kumar; Gandra, Suchithra; Shastri, Nalini R

2016-03-10

The objective of the study was to design and optimize a disintegrating pellet formulation of microcrystalline cellulose by non-aqueous extrusion process for a water sensitive drug using various statistical tools. Aspirin was used as a model drug. Disintegrating matrix pellets of aspirin using propylene glycol as a non-aqueous granulation liquid and croscarmellose as a disintegrant was developed. Plackett-Burman design was initially conducted to screen and identify the significant factors. Final optimization of formula was performed by response surface methodology using a central composite design. The critical attributes of the pellet dosage forms (dependent variables); disintegration time, sphericity and yield were predicted with adequate accuracy based on the regression model. Pareto charts and contour charts were studied to understand the influence of factors and predict the responses. A design space was constructed to meet the desirable targets of the responses in terms of disintegration time <5min, maximum yield, sphericity >0.95 and friability <1.7%. The optimized matrix pellets were enteric coated using Eudragit L 100. The drug release from the enteric coated pellets after 30min in the basic media was ~93% when compared to ~77% from the marketed pellets. The delayed release pellets stored at 25°C/60% RH were stable for a period of 10mo. In conclusion, it can be stated that the developed process for disintegrating pellets using non-aqueous granulating agents can be used as an alternative technique for various water sensitive drugs, circumventing the application of volatile organic solvents in conventional drug layering on inert cores. The scope of this study can be further extended to hydrophobic drugs, which may benefit from the rapid disintegration property and the use of various hydrophilic excipients used in the optimized pellet formulation to enhance dissolution and in turn improve bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

PubMed

Tanaka, Hironori; Iwao, Yasunori; Izumikawa, Masahiro; Sano, Syusuke; Ishida, Hitoshi; Noguchi, Shuji; Itai, Shigeru

2016-01-01

In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution

PubMed Central

Balata, Gehan F; Zidan, Ahmad S; Abourehab, Mohamad AS; Essa, Ebtessam A

2016-01-01

The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene–polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT’s porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin. PMID:27757012

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

PubMed

de Alencar, Rodrigo Gomes; de Oliveira, Aline Carlos; Lima, Eliana Martins; da Cunha-Filho, Marcílio Sérgio Soares; Taveira, Stephânia Fleury; Marreto, Ricardo Neves

2017-08-01

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated. Pellets were prepared via extrusion-spheronization and coated using two acrylic polymers (Eudragit® FS 30 D and Opadry® 94 k28327, PMMA and PMA, respectively). The resulting pellets were mixed with placebo granules and compressed in a hydraulic press. Multiple regression showed that ketoprofen release from pellet-containing tablets is predominantly influenced by pellet content, hardness, friability, and disintegration time. PMA-containing tablets prepared under low compaction force or with low pellet content showed rapid disintegration (<1 min) and ketoprofen release similar to those of uncompressed coated pellets (∼30% at 360 min of experiment). On the other hand, PMMA-containing tablets showed a higher rupture level, and those prepared with higher pellet content gave rise to a non-disintegrating matrix. Coated pellets were shown to be able to target ketoprofen to the colonic region. Targeting capacity was dependent on the physicochemical characteristics of the tablets.

Orodispersible tablets: A new trend in drug delivery

PubMed Central

Dey, Paramita; Maiti, Sabyasachi

2010-01-01

The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug-delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test. PMID:22096326

Design and evaluation of an economic taste-masked dispersible tablet of pyridostigmine bromide, a highly soluble drug with an extremely bitter taste.

PubMed

Tan, Qunyou; Zhang, Li; Zhang, Liangke; Teng, Yongzhen; Zhang, Jingqing

2012-01-01

Pyridostigmine bromide (PTB) is a highly soluble and extremely bitter drug. Here, an economic complexation technology combined with direct tablet compression method has been developed to meet the requirements of a patient friendly dosage known as taste-masked dispersible tablets loaded PTB (TPDPTs): (1) TPDPTs should have optimal disintegration and good physical resistance (hardness); (2) a low-cost, simple but practical preparation method suitable for industrial production is preferred from a cost perspective. Physicochemical properties of the inclusion complex of PTB with beta-cyclodextrin were investigated by Fourier transformed infrared spectroscopy, differential scanning calorimetry and UV spectroscopy. An orthogonal design was chosen to properly formulate TPDPTs. All volunteers regarded acceptable bitterness of TPDPTs. The properties including disintegration time, weight variation, friability, hardness, dispersible uniformity and drug content of TPDPTs were evaluated. The dissolution profile of TPDPTs in distilled water exhibited a fast rate. Pharmacokinetic results demonstrated that TPDPTs and the commercial tablets were bioequivalent.

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.

Rapidly-disintegrating sublingual tablets of epinephrine: role of non-medicinal ingredients in formulation development.

PubMed

Rachid, Ousama; Rawas-Qalaji, Mutasem; Simons, F Estelle R; Simons, Keith J

2012-11-01

Epinephrine is the drug of choice in the management of anaphylaxis. For first-aid treatment in the community, epinephrine autoinjectors (E-autos) are commonly prescribed, but are underutilized. In our laboratory, we developed a series of first-generation rapidly-disintegrating sublingual tablets (RDSTs) containing 40mg of epinephrine. One RDST had similar bioavailability to epinephrine 0.3mg from an auto-injector, as confirmed in a validated rabbit model, while other formulations containing different non-medicinal ingredients (NMIs) and with similar in vitro characteristics demonstrated much lower bioavailability. Subsequently, we evaluated the effect of changing the grade and proportion of NMIs, specifically mannitol and microcrystalline cellulose (MCC), on the in vitro characteristics of second- and third-generation RDSTs. Weight variation, content uniformity, breaking force, and friability were tested using official USP methods. Novel validated methods that simulate ambient conditions of the sublingual cavity were developed to test disintegration time, wetting time, and dissolution. Using these methods, it was possible to measure the effects of making small changes in NMIs on the in vitro characteristics of the formulations. The RDST formulation that resulted in the best in vitro characteristics contained the optimum proportion of mannitol and a specific ratio of coarse and fine particle grades of MCC. Appropriate comparative testing resulted in the selection of the RDST with the optimum in vitro characteristics. Copyright © 2012 Elsevier B.V. All rights reserved.

[Method for the evaluation of the stability and usability after opening packages of orally disintegrating tablets: case of amlodipine besilate products].

PubMed

Hori, Katsuhito; Yoshida, Naoko; Okumura, Tomonori; Okamura, Yasufumi; Kawakami, Junichi

2010-08-01

Orally disintegrating (OD) tablets are widely used in clinical practice. However, drug information on the choice and dispensing based on their stability after opening packages and usability in patients and dispensaries is not sufficient. The aim of this study was to investigate possible evaluation methods of the stability and usability of amlodipine OD tablets. Additives of the brand were changed in April 2009, and therefore the previous and current forms and two generics, current and newly marketed (in November 2009) products of different firms, were used. OD tablets were stored at 25 degrees C and 75% relative humidity for 3 months after opening the packages, and their physicochemical properties were evaluated. Their weight, diameter, thickness, and color difference increased slightly from the initial state. The extent of the change in their hardness, disintegration time, and friability was different among products. These physicochemical changes were acceptable in dispensary practice. Storage after opening the packages did not affect their dissolution rate. The dissolution rate at the initial state of the current brand was slower than that of the previous one. All products used were able to be dispensed by an automatic tablet-packing machine and applied to the so-called simple suspension method for intubational administration. Sensory evaluation tests revealed no major difference in the oral disintegration time, taste, impression, and preference among products. In conclusion, the stability and usability of amlodipine OD tablets used in this study were examined using several methods, and they can be used equivalently from the stability and usability viewpoints.

The Effects of Screw Configuration and Polymeric Carriers on Hot-Melt Extruded Taste-Masked Formulations Incorporated into Orally Disintegrating Tablets

PubMed Central

Morott, Joseph T.; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P.; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A.

2015-01-01

The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

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.

IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

PubMed

Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

2016-01-01

In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Besides that, gliclazide was also compatible with the excipients used. Chickpea starch acted as a disintegrant in gliclazide IR tablets, instead of a binder. Therefore, chickpea starch can be a promising disintegrant in gliclazide IR tablets.

[The Use of Synthetic Polymers (Superdisintegrants) in Technology Tablets Containing Ethanol Dry Extract from Asparagus officinalis].

PubMed

Linka, Wojciech Andrzej; Wojtaszek, Ilona; Zgoda, Marian Mikołaj; Kołodziejczyk, Michał Krzysztof

2015-01-01

Dry extracts are now frequently used in medicine as an alternative to synthetic drugs. In the case of tablet technology with dry plant extracts, the proper selection of disintegrants (superdisintegrants) is particularly important. Objectives. The aim of this study was to evaluate the usefulness of the polymers constituting superdisintegrants (Vivasol®, Vivastar®, Polyplasdone XL) in uncoated tablet formulation of alcoholic extracted from Asparagus officinalis. Dry the ethanol extract of Asparagus officinalis, Vivasol®, Vivastar®, Vivapur®, Kollidon VA64, Polyplasdone XL, magnesium stearate. Direct compression. Paddle method was carried out to study pharmacopoeial parameters and pharmaceutical availability. The calculation of equivalency factors: similarity [f2] and the difference [f1]. Approximation results. Tablets brownish-green, with a smooth and uniform surface, without stains, chipping and damage. The determined average weight of the tablets compiled with the standards. The test friability and crushing strength revealed that the most mechanically strong tablets contained Vivasol, Vivastar, Polyplasdone XL. These tablets also have a longer disintegration and dissolution time compared with tablets containing only Vivasol. These differences are also confirmed by the calculated f2 and f1. The addition of a mixture of Polyplasdone XL and Vivastar to Vivasol significantly increases the mechanical strength of the tablets (crushing strength, resistance to crushing). The addition of a mixture of Polyplasdone XL and Vivastar to Vivasol paradoxically increases the disintegration time of tablets (11.1 min). Single superdisintegrant breaks up the tablet more effectively than a mixture of superdisintegrants.

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.

Impact of chitosan as a disintegrant on the bioavailability of furosemide tablets: in vitro evaluation and in vivo simulation of novel formulations.

PubMed

Rasool, Bazigha Kadhim Abdul; Fahmy, Sahar Abdelsattar; Galeel, Omar Waleed Abdul

2012-10-01

To determine the effect of chitosan, starch powder, polyvinylpyrrolidone (PVP), Avicel PH 101 powder, Avicel PH 102 granules as a function of different concentrations on the solubility, disintegration and hence dissolution of furosemide from immediate release tablet dosage forms. The tablets were prepared by the wet granulation method and evaluated for hardness, friability, disintegration and in vitro dissolution. Chitosan 7% w/w showed the fastest disintegration of furosemide tablets among the other disintegrants studied. This was attributed to its highest swelling properties and velocity constant of water uptake. The step of adding chitosan during tablet preparation had a great effect on the physical properties and dissolution profiles of the prepared tablets with external addition of chitosan showed best results compared to best results comparing to internal-external or internal addition. The most appropriate force of compression was 4ton/cm(2). The selected formula F15 containing 7% w/w chitosan was successful and showed a high significant (p<0.001) enhancement in disintegration and dissolution behaviors of furosemide tablets in comparison with the commercially available Furosemide ® tablets. These results were supported by the simulated data where F15 formula showed the highest plasma concentration C-max 1.89mcg/mL after 0.5 hr compared to C-max 1.05mcg/mL after 1hr for the reference. The present study demonstrated that chitosan is a very good candidate to be used as a tablet disintegrant and was able to enhance the dissolution of poorly absorbable drugs.

Fingerprints, Pharmaceutical and Radical Scavenging Activity Evaluation of an Alzheimer-Targeted Herbal Preparation.

PubMed

Dabaghian, Farid; Khademian, Sedigheh; Azadi, Amir; Zarshenas, Mohammad

2016-05-01

As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC50 >100 µg/ml) was calculated for the methanol extract of tablets. Carrying out and validating a GC method for standardization of the formulated tablet, and having the structure for the effectiveness of these medicinal herbs in Alzheimer may be the horizon for a new Alzheimer-targeted medicine.

Fingerprints, Pharmaceutical and Radical Scavenging Activity Evaluation of an Alzheimer-Targeted Herbal Preparation.

PubMed

Dabaghian, Farid; Khademian, Sedigheh; Azadi, Amir; Zarshenas, Mohammad

2016-05-01

As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC 50 >100 µg/ml) was calculated for the methanol extract of tablets. Carrying out and validating a GC method for standardization of the formulated tablet, and having the structure for the effectiveness of these medicinal herbs in Alzheimer may be the horizon for a new Alzheimer-targeted medicine.

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.

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.

Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor® El-Based Liquisolid Tablets

PubMed Central

Yehia, Soad Ali; El-Ridi, Mohamed Shafik; Tadros, Mina Ibrahim; El-Sherif, Nolwa Gamal

2015-01-01

Purpose: The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax). Methods: Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor® EL (CR)], (ii) carrier [Avicel® PH102] to coat [Aerosil® 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carr’s index, Hausner’s ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 – 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra® tablets. Results: Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min. Conclusion: LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h. PMID:26819931

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.

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion.

PubMed

Sammour, Omaima A; Hammad, Mohammed A; Megrab, Nagia A; Zidan, Ahmed S

2006-06-16

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.

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.

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

Development of taste masked caffeine citrate formulations utilizing hot melt extrusion technology and in vitro-in vivo evaluations

PubMed Central

Pimparade, Manjeet. B.; Morott, Joseph T.; Park, Jun-Bom; Kulkarni, Vijay I.; Majumdar, Soumyajit; Murthy, S. N.; Lian, Zhuoyang; Pinto, Elanor; Bi, Vivian; Durig, Thomas; Murthy, Reena; Shivakumar, H.N; Vanaja, K.; Kumar, C. P; Repka, Michael A.

2015-01-01

The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release. A modified screw configuration was applied to improve the extrusion processability and to preserve the crystallinity of the API. The milled extrudates were subjected to dissolution testing in an artificial salivary fluid and investigations using e-tongue, to assess the extent of masking of bitter taste of the API. There was an insignificant amount of drug released from the formulation in the salivary medium while over 80% of drug released within 30 min in 0.1 N HCl. ODTs were also developed with the extrudate mixed with mannitol and crospovidone. The quality properties such as friability and disintegration time of the ODTs met the USP specifications. The lead extrudate formulations and the ODTs prepared using this formulation were subjected to human gustatory evaluation. The formulations were found to mask the unpleasant taste of caffeine citrate significantly. PMID:25888797

Quality-by-design approach for the development of telmisartan potassium tablets.

PubMed

Oh, Ga-Hui; Park, Jin-Hyun; Shin, Hye-Won; Kim, Joo-Eun; Park, Young-Joon

2018-05-01

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis ® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis ® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis ® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis ® tablets in beagle dogs.

Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets.

PubMed

Arafat, Basel; Wojsz, Magdalena; Isreb, Abdullah; Forbes, Robert T; Isreb, Mohammad; Ahmed, Waqar; Arafat, Tawfiq; Alhnan, Mohamed A

2018-06-15

Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and evaluation of orally disintegrating tablets comprising taste-masked mirtazapine granules.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Vural, İmran; Ünlü, Nurşen

2018-06-01

Orally disintegrating tablets (ODTs) provide an important treatment option for pediatric, geriatric and psychiatric patients. In our previous study, we have performed the initial studies for the formulation development and characterization of new ODT formulations containing a bitter taste drug, mirtazapine, coated with 6% (w/w) Eudragit ® E-100 (first group of formulations, FGF) without taste evaluation. In present study, coating ratio of the drug was increased to 8% (w/w) (second group of formulations, SGF) to examine the effect of increased coating ratio of drug on in vitro characterization of the formulations including in vitro taste masking study. Coacervation technique using Eudragit ® E-100 was employed to obtain taste-masked mirtazapine granules. FGF and SGF were compared to original product (Remeron SolTab, an antidepressant drug which produced by pellet technology) in terms of in vitro permeability, in vitro taste masking efficiency which was performed by dissolution studies in salivary medium and dissolution stability. Also, the other tablet characteristics (such as diameter, thickness) of SGF were examined. The disintegration time of the SGF were found as A1 < A2 < A3 < A5 < A4 (8% Eudragit ® E-100), but all of the formulations dissolved under 30 seconds and friability values were less than 1%. In vitro taste masking efficiency studies demonstrated that C2 formulation (in FGF) had the most similar dissolution profile to Remeron SolTab. According to these findings, B2 or C2 (with citric acid or sodium bicarbonate, respectively, with 6% Eudragit ® E-100) formulations could be promising alternatives to Remeron SolTab.

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.

Formulation and evaluation of microsphere based oro dispersible tablets of itopride hcl

PubMed Central

2012-01-01

Background The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. Methods With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. Results The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Conclusions Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics. PMID:23351176

Formulation and evaluation of microsphere based oro dispersible tablets of itopride hcl.

PubMed

Shah, Sanjay; Madan, Sarika; Agrawal, Ss

2012-09-03

The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics.

Formulation and evaluation of sublingual tablets containing Sumatriptan succinate

PubMed Central

Prajapati, Shailesh T; Patel, Parth B; Patel, Chhagan N

2012-01-01

Objective: Sumatriptan succinate is a selective 5-hydroxytryptamine-1 receptor agonist effective in the acute treatment of migraine headaches, having low bioavailability of about 15% orally due to first-pass metabolism. The purpose of this research was to mask the intensely bitter taste of Sumatriptan succinate and to formulate fast-acting, taste-masked sublingual tablet formulation. Materials and Methods: Taste masking was performed by solid dispersion method with mannitol and ion exchange with Kyron T 114 because it releases the drug in salivary pH. The resultant batches were evaluated for in-vivo taste masking as well compatability study (Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC)). For a better feel in the mouth, menthol and sweetener Na saccharine were added to the tablet formulation. The tablets were prepared by direct compression and evaluated for weight variation, thickness, friability, drug content, hardness, disintegration time, wetting time, in vitro drug release, and in vitro permeation study. Results and Discussion: Optimized batches disintegrated in vitro within 28-34 s. Maximum drug release could be achieved with in 10 min for the solid dispersion batches and 14-15 min for the ion-exchange batches with Kyron T 114. The optimized tablet formulation showed better taste and the formulated sublingual tablets may act as a potential alternate for the Sumatriptan succinate oral tablet. Conclusion: Sumatriptan succinate can be successfully taste-masked by both the solid dispersion method using mannitol by the melting method and Ion exchange resin with Kyron T114. It was also concluded that prepared formulation improve bioavailability by prevention of first pass metabolism. PMID:23373008

3D extrusion printing of high drug loading immediate release paracetamol tablets.

PubMed

Khaled, Shaban A; Alexander, Morgan R; Wildman, Ricky D; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J

2018-03-01

The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of the direct compression aid Ludiflash(®) for the preparation of pellets via wet extrusion/spheronization.

PubMed

Roblegg, Eva; Schrank, Simone; Griesbacher, Martin; Radl, Stefan; Zimmer, Andreas; Khinast, Johannes

2011-10-01

Conventional solid oral dosage forms are unsuitable for children due to problems associated with swallowing and unpleasant taste. Additionally, the limit of tablets lays in the patient adapted dosing. Therefore, the suitability of Ludiflash(®), a direct compression aid for orally disintegrating tablets, was investigated for the preparation of individually dosable pellets. Micropellets consisting of Ludiflash(®) and small amounts of microcrystalline cellulose were prepared via the wet extrusion/spheronization technique. Paracetamol and ibuprofen were applied as model drugs. The obtained pellets were characterized with respect to drug release and disintegration characteristics, mechanical properties, as well as size and shape. Drug loading was possible up to 30% for ibuprofen and even up to 50% for paracetamol. Higher ibuprofen loadings resulted in considerably slowed drug release and higher paracetamol contents yielded in non-spherical pellets. In vitro release studies revealed that more than 80% of the drug was released within 30 and 60 min for paracetamol and ibuprofen, respectively. Drug release rates were highly influenced by the pellet disintegration behavior. Investigations of the release mechanism using the Korsemeyer-Peppas approach suggested Super Case II drug transport for all paracetamol formulations and anomalous drug transport for most ibuprofen formulations. All pellets exhibited a low porosity and friability, as well as a sufficiently high tensile strength, which was significantly influenced by the type of model drug. Ludiflash(®) can be applied as main excipient for the preparation of individually dosable pellets combining fast drug release and a high mechanical stability.

Powder and compaction characteristics of pregelatinized starches.

PubMed

Rojas, J; Uribe, Y; Zuluaga, A

2012-06-01

Pregelatinized starch is widely used as a pharmaceutical aid, especially as a filler-binder. It is known that the tableting performance of excipients could be affected by their source. The aim of this study was to evaluate the powder and tableting properties of pregelatinized starches obtained from yucca, corn and rice and compare those properties with those of Starch 1500. This material had the lowest particle size, and porosity and largest density and best flow. However, yucca starch and corn starch showed an irregular granule morphology, better compactibility and compressibility than Starch 1500. Their onset of plastic deformation and their strain rate sensitivity was comparable to that of Starch 1500. These two materials showed compact disintegration slower that Starch 1500. Conversely, rice starch showed a high elasticity, and friability, low compactibility, which are undesirable for direct compression. This study demonstrated the potential use of pregelatinized starches, especially those obtained from yucca and corn as direct compression filler-binders.

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.

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

PubMed

Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

2016-01-01

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Clinical disintegration time of orally disintegrating tablets clinically available in Japan in healthy volunteers.

PubMed

Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

2013-01-01

Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; p<0.001). This study shows that all the tested products, which are clinically available in Japan, showed good disintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity.

Evaluation of disintegration properties of orally rapidly disintegrating tablets using a novel disintegration tester.

PubMed

Kondo, Keita; Niwa, Toshiyuki; Danjo, Kazumi

2012-01-01

This report describes a new disintegration tester that can determine not only the disintegration time of orally rapidly disintegrating tablets (ODT), but also the disintegration behavior and mechanism. Using the tester, the disintegration properties of the tablets prepared in a previous study were examined. The purpose of this study is to confirm the utility of the tester as an instrument for evaluating the disintegration properties of ODT and determine relations among time, behavior and mechanism of the disintegration. Results demonstrated that in vitro disintegration time in the tester is similar to that in the commercial disintegration tester for ODT and is highly correlated with oral disintegration time. Observations of disintegration process revealed that a difference in disintegration behavior between tablets compressed at 50-75 MPa and 100 MPa; the disintegration behavior of the tablets were designated immediate disintegrating type and gradual disintegrating type, respectively. The dynamic swelling profile and water absorption profile indicated that the disintegration mechanism of the tablets involved wicking action induced by swelling of the disintegrant; the disintegration time was closely related to the initial rates of swelling and water absorption. Furthermore, the mechanism of water absorption of tablets compressed at 50-75 MPa and 100 MPa shows anomalous diffusion and case-II transport, respectively. The shift in this mechanism is consistent with differences in disintegration time and behavior between the tablets. These findings suggest that information on disintegration properties obtained by our tester is useful for understanding of disintegration phenomena of ODT.

Design, Development and Rationalization of Sarpagandha Ghanvati

PubMed Central

Pundarikakshudu, K.; Bhatt, C. J.

2015-01-01

Sarpagandha ghanvati is a classical Ayurvedic formulation widely prescribed for anxiety and insomnia. It contains Sarpagandha (roots of Rauwolfia serpentina L. (Benth.) Ex Kurz; Family: Apocyanaceae), Khurasani ajowan (Hyocyamus niger L.; Family: Solanaceae) seeds, Jatamansi (Nardostachys jatamansi DC. Family: Valerianaceae) roots and Pipplamul (root of Piper longum L.; Family: Piperaceae). The objective of this study was to make a comparative evaluation of Ghanvatis and tablets of this formulation. Two tablet formulations were prepared; one incorporating only powders of all ingredients; the other with ethanol extracts of the first three ingredients and powder of Piper longum root. Similarly, two types of Sarpagandha ghanvati pills were prepared; one as per Ayurvedic Formulary of India; the other with ethanol extracts of the first three ingredients and powder of Piper longum root. Alcohol extracted 0.22% w/w of total alkaloids as against 0.061% w/w extracted by water. Tablets prepared with powders of all the ingredients had friability more than 3.0% where as those prepared with ethanol extract had very low friability. Ghanvatis, prepared as per the Ayurvedic formulary, did not show reserpine although other alkaloids were present. They showed less content uniformity and lower drug release. Ethanol extracted reserpine along with other alkaloids. Ghanvatis made with the alcoholic extracts exhibited better content uniformity and drug release than the traditional formulation. Tablets prepared with powders or extracts of the ingredients exhibited good content uniformity but the release of alkaloids from the tablets of powders was only 80%. Tablets of the extracts had good content uniformity with 90% release of the total alkaloids. Tablets prepared with alcoholic extracts using 1% polyvinylpyrrolidone as binder and 5% dried starch powder as disintegrating agent confirmed to all the requirements. Thus, the study shows tablets made with the extracts are superior to Ghanvatis and powder tablets. PMID:26798180

Evaluation of different fast melting disintegrants by means of a central composite design.

PubMed

Di Martino, Piera; Martelli, Sante; Wehrlé, Pascal

2005-01-01

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X1) and the compression force (X2). These factors were studied for tablets containing either Zeparox or Pearlitol 200 as soluble diluents and six different disintegrants: L-HPC LH11 and LH31, Lycatab PGS, Vivasol, Kollidon CL, and Explotab. Their micromeritics properties were previously determined. The response variables were disintegration time (Y1), tensile strength (Y2), and porosity (Y3). Whatever the diluent, the longest disintegration time is obtained with Vivasol as the disintegrant, while Kollidon CL leads to the shortest disintegration times. Exception for Lycatab PGS and L-HPC LH11, formulations with Pearlitol 200 disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox as the diluent when compared to Pearlitol 200 and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200 is used with Vivasol, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox, the interaction between the two controlled variables is more complex: there is no effect of compression force on the disintegration time for a small amount of disintegrant, but a significant increase for higher concentrations. With Kollidon CL, the main factor influencing the disintegration time is the compression force, rather than the disintegrant concentration. Increasing both the compression force and the disintegrant concentration leads to an increase of the disintegration time. For lower Kollidon CL percentages, the compression pressure increases dramatically the tablet disintegration. With the Explotab, whatever the increase of compression force, the disintegrant concentration leads to an increase of the disintegration time. According to Student's t-test, only the compression force significantly and strongly influences the disintegration time when Pearlitol 200 is used. A slight interaction and some trends nevertheless appear: above 150 MPa, increasing the disintegrant concentration leads to a shortened disintegration time, below this limit the opposite effect is observed.

Enhanced dissolution of sildenafil citrate as dry foam tablets.

PubMed

Sawatdee, Somchai; Atipairin, Apichart; Sae Yoon, Attawadee; Srichana, Teerapol; Changsan, Narumon

2017-01-30

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5 kg, friability test <1% with a disintegration time <5 min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.

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

Functionality of disintegrants and their mixtures in enabling fast disintegration of tablets by a quality by design approach.

PubMed

Desai, Parind Mahendrakumar; Er, Patrick Xuan Hua; Liew, Celine Valeria; Heng, Paul Wan Sia

2014-10-01

Investigation of the effect of disintegrants on the disintegration time and hardness of rapidly disintegrating tablets (RDTs) was carried out using a quality by design (QbD) paradigm. Ascorbic acid, aspirin, and ibuprofen, which have different water solubilities, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modeled by executing combined optimal design. The generated models were validated and used for further analysis. Sodium starch glycolate, croscarmellose sodium, and crospovidone were found to lengthen disintegration time when utilized at high concentrations. Sodium starch glycolate and crospovidone worked synergistically in aspirin RDTs to decrease disintegration time. Sodium starch glycolate-crospovidone mixtures, as well as croscarmellose sodium-crospovidone mixtures, also decreased disintegration time in ibuprofen RDTs at high compression pressures as compared to the disintegrants used alone. The use of sodium starch glycolate in RDTs with highly water soluble active ingredients like ascorbic acid slowed disintegration, while microcrystalline cellulose and crospovidone drew water into the tablet rapidly and quickened disintegration. Graphical optimization analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD was an efficient and effective paradigm in understanding formulation and process parameters and building quality in to RDT formulated systems.

In vitro disintegration studies of weekly generic and branded risedronate sodium formulations available in Canada.

PubMed

Walker, A D; Adachi, J D

2011-09-01

The aim of this study was to evaluate the in vitro disintegration of the five newly available Canadian generic risedronate 35 mg tablets compared to the innovator (branded) product, ACTONEL * *ACTONEL is a registered trade name of Warner Chilcott Company, LLC. (risedronate sodium) 35 mg. Tablets were inspected for colour and appearance. Disintegration times were determined using United States Pharmacopeia 33 (USP33-NF 28) methods. Disintegration onset time was also evaluated. The mean disintegration onset time values for the generic risedronate 35 mg tablets ranged from 2 to 29 seconds, and the mean disintegration completion times ranged from 81 to 260 seconds. The mean disintegration onset and completion time values for the ACTONEL 35 mg tablets were 23 and 43 seconds respectively. Four out of the five generic tablets tested had shorter disintegration onset times than the branded product; two of the generic tablet products had very fast disintegration onset times i.e. 2-3 seconds. Disintegration completion time for all five generic products tested was longer than that observed for the branded product; two generic products had disintegration completion time values five to six times longer than the branded product. Differences in the in vitro disintegration times were observed between the generic risedronate 35 mg tablets commercially available in Canada and the branded product, ACTONEL. The rapid disintegration onset times of two generic products may be important as this could increase the possibility of drug exposure in both the mouth and the esophagus during swallowing, resulting in unwanted localized irritation. However, it should be noted that an in vitro/in vivo correlation has not been established. Until such studies are completed it may be important to be aware of such in vitro disintegration differences when evaluating patients with newly presenting upper gastrointestinal complaints upon being switched from the branded product to generic formulations.

Chronomodulated drug delivery system of urapidil for the treatment of hypertension

PubMed Central

Chaudhary, Sona S.; Patel, Hetal K.; Parejiya, Punit B.; Shelat, Pragna K.

2015-01-01

Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension. PMID:25838996

Formulation development and optimization: Encapsulated system of Atenolol and Glyburide.

PubMed

Maboos, Madiha; Yousuf, Rabia Ismail; Shoaib, Muhammad Harris

2016-03-01

Objective of this study is to develop; tablet-in-a capsule system, to deliver Atenolol 25mg and Glyburide 5mg in the hard gelatin capsule. In order to improve patient compliance and reduce problems associated with complex therapeutic regimen Atenolol (cardio-selective beta-blocker) and Glyburide (anti-diabetic; sulfonylurea) are commonly, prescribed to the diabetic hypertensive patient. Metgod: In present work six different formulations of Atenolol (AF1-AF6) and Glyburide (GF1-GF6) were prepared by direct compression method using Avicel, Lactose DC, Crospovidone and Magnesium Stearate in different proportions and encapsulated in hard gelatin shells. Post compression parameters i.e. weight variation, diameter variation, thickness variation, hardness variation, % friability, disintegration, % drug release were determined at different pH 1.2, 4.5 and 6.8, and subjected to dissolution profile comparison through similarity factor (ƒ2). Stability studies were performed and shelf lives were calculated by R-Gui Stab R console 2.15.2 and determined to be 15 and 27 months for Atenolol and Glyburide respectively. The percentage drug contents of Atenolol and Glyburide were estimated spectrophotometerically at 286 nm and 314.7 nm respectively. Formulations CF1-CF6 (encapsulated) were subjected to weight variation, disintegration and dissolution tests and subjected to model dependant analysis for dissolution studies. The simultaneous quantitation of Atenolol and Glyburide for content assay was done by HPLC method of analysis. formulation CF6 is showing highest coefficient of correlation values for all models applied. So we can conclude that the proposed system can improve patient compliance by increasing the ease of administration of two drugs together.

The effect of glicerol and sorbitol plasticizers toward disintegration time of phyto-capsules

NASA Astrophysics Data System (ADS)

Pudjiastuti, Pratiwi; Hendradi, Esti; Wafiroh, Siti; Harsini, Muji; Darmokoesoemo, Handoko

2016-03-01

The aim of research is determining the effect of glycerol and sorbitol toward the disintegration time of phyto-capsules, originated capsules from plant polysaccharides. Phyto-capsules were made from polysaccharides and 0.5% (v/v) of glycerol and sorbitol of each. The seven capsules of each were determined the disintegration time using Erweka disintegrator. The mean of disintegration time of phyto-capsules without plasticizers, with glycerol and sorbitol were 25'30"; 45'15" and 35'30" respectively. The color and colorless gelatin capsules showed the mean of disintegration time 7'30" and 2'35" respectively.

Functional assessment of four types of disintegrants and their effect on the spironolactone release properties.

PubMed

Rojas, John; Guisao, Santiago; Ruge, Vanesa

2012-12-01

Spironolactone is a drug derived from sterols that exhibits an incomplete oral absorption due to its low water solubility and slow dissolution rate. In this study, formulations of spironolactone with four disintegrants named as croscarmellose sodium, crospovidone, sodium starch glycolate and microcrystalline cellulose II (MCCII) were conducted. The effect of those disintegrants on the tensile strength, disintegration time and dissolution rate of spironolactone-based compacts was evaluated using a factorial design with three categorical factors (filler, lubricant, and disintegrant). The swelling values, water uptake and water sorption studies of these disintegrants all suggested that MCCII compacts disintegrate by a wicking mechanism similar to that of crospovidone, whereas a swelling mechanism was dominant for sodium starch glycolate and croscarmellose sodium. The disintegration time of MCCII and sodium starch glycolate remained unchanged with magnesium stearate. However, this lubricant delayed the disintegration time of crospovidone and croscarmellose sodium. MCCII presented the fastest disintegration time independent of the medium and lubricant employed. The water sorption ratio and swelling values determined sodium starch glycolate followed by croscarmellose sodium as the largest swelling materials, whereas crospovidone and MCCII where the least swelling disintegrants. The swelling property of sodium starch glycolate and croscarmellose sodium was strongly affected by the medium pH. The disintegration time of spironolactone compacts was faster when starch was used as a filler due to the formation of soft compacts. In this case, the type of filler employed rather than the disintegrant had a major effect on the disintegration and dissolution times of spironolactone.

Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

PubMed Central

Labib, Gihan S

2015-01-01

Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426

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.

In vitro disintegration studies of weekly generic alendronate sodium tablets (70 mg) available in the US.

PubMed

Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

2009-02-01

Bisphosphonates as a class have the potential to cause upper gastrointestinal irritation. Although the generic alendronate sodium tablets are bioequivalent to the branded product, a potential concern is that the pharmaceutical attributes of the various generic formulations my affect the potential for local irritation and tolerability. The in vitro disintegration times were determined using the method described in the US Pharmacopeia 30 (USP 30). The disintegration of three generic alendronate sodium tablets 70 mg available in the United States was compared to that of the branded product. The mean disintegration times of the generic alendronate sodium tablets ranged from 9 to 10 s for the Barr lots to 108 s for the Watson lot. The disintegration time of the branded product (Fosamax) was 53 s. The three Barr lots and one Teva lot had rapid disintegration times which were similar to the disintegration standards (< 30 s) for orally disintegrating tablets. Since there is no established disintegration time for alendronate sodium tablets there can be no assurance that the generic tablets are equivalent to the branded product in terms of esophageal exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration performance. Copies of generic alendronate sodium tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not considered adequate to establish similar disintegration characteristics.

Evaluation of the palatabilities in 10 different famotidine orally disintegrating tablets by combination of disintegration device and taste sensor.

PubMed

Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro

2015-01-01

The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.

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 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

Standardization of the finished product: Habbe Irqun Nisa - A Unani anti-inflammatory formulation.

PubMed

Husain, S Farhan; Ahmad, Irshad; Shamsi, Shariq

2012-07-01

Habb (Pill) is one of the important dosage forms of Unani system of medicine. A number of effective formulations are manufactured in form of Habb because of its various advantages. Out of these, Habbe Irqun Nisa (HI) is a popular anti-inflammatory formulation used in the treatment of Warame Mafasil (arthritis) and Irqun Nisa (sciatica). Nowadays, with increased incidence of these diseases many non-steroidal anti-inflammatory drugs (NSAIDs) are being used in their treatment. Owing to the adverse effects of these drugs, the use of herbal medicines is seen as a better alternative. The basic requirement for the development of Unani system of Medicine is the standardization of single and compound drugs. HI is mentioned in National Formulary of Unani Medicne and selected for the present study. HI was prepared manually with the powder of crude drugs, passed through sieve no. 100 and mixed with 1% w/w of gum acacia in mucilage form. It was then dried at 60°C for 90 min and then tested for its standardization on different physicochemical parameters, e.g. organoleptic properties, pH values, moisture content, ash values, friability, hardness, weight variation, disintegration time, and thin layer chromatography (TLC). The data evolved from this study will make it a validated product and will help in the quality control of other finished products in future research.

Varying efficacy of superdisintegrants in orally disintegrating tablets among different manufacturers.

PubMed

Mittapalli, R K; Qhattal, H S Sha; Lockman, P R; Yamsani, M R

2010-11-01

The main objective of the present study was to develop an orally disintegrating tablet formulation of domperidone and to study the functionality differences of superdisintegrants each obtained from two different sources on the tablet properties. Domperidone tablets were formulated with different superdisintegrants by direct compression. The effect of the type of superdisintegrant, its concentration and source was studied by measuring the in-vitro disintegration time, wetting time, water absorption ratios, drug release by dissolution and in-vivo oral disintegration time. Tablets prepared with crospovidone had lower disintegration times than tablets prepared from sodium starchglycolate and croscarmellose sodium. Formulations prepared with Polyplasdone XL, Ac-Di-Sol, and Explotab (D series) were better than formulations prepared with superdisintegrants obtained from other sources (DL series) which had longer disintegration times and lower water uptake ratios. The in-vivo disintegration time of formulation D-106 containing polyplasdone XL was significantly lower than that of the marketed formulation Domel-MT. The results from this study suggest that disintegration of orally disintegrating tablets is dependent on the nature of superdisintegrant, concentration in the formulation and its source. Even though a superdisintegrant meets USP standards there can be a variance among manufacturers in terms of performance. This is not only limited to in-vitro studies but carries over to disintegration times in the human population.

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.

Assessment of disintegrant efficacy with fractal dimensions from real-time MRI.

PubMed

Quodbach, Julian; Moussavi, Amir; Tammer, Roland; Frahm, Jens; Kleinebudde, Peter

2014-11-20

An efficient disintegrant is capable of breaking up a tablet in the smallest possible particles in the shortest time. Until now, comparative data on the efficacy of different disintegrants is based on dissolution studies or the disintegration time. Extending these approaches, this study introduces a method, which defines the evolution of fractal dimensions of tablets as surrogate parameter for the available surface area. Fractal dimensions are a measure for the tortuosity of a line, in this case the upper surface of a disintegrating tablet. High-resolution real-time MRI was used to record videos of disintegrating tablets. The acquired video images were processed to depict the upper surface of the tablets and a box-counting algorithm was used to estimate the fractal dimensions. The influence of six different disintegrants, of different relative tablet density, and increasing disintegrant concentration was investigated to evaluate the performance of the novel method. Changing relative densities hardly affect the progression of fractal dimensions, whereas an increase in disintegrant concentration causes increasing fractal dimensions during disintegration, which are also reached quicker. Different disintegrants display only minor differences in the maximal fractal dimension, yet the kinetic in which the maximum is reached allows a differentiation and classification of disintegrants. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of the in vivo disintegration of solid dosage forms of a bile acid sequestrant in dogs using gamma-scintigraphy and correlation to in vitro disintegration.

PubMed

Hussain, Munir A; Chang, Rong-Kun; Sandefer, Erik; Page, Richard C; Digenis, George A

2003-03-01

[corrected] To evaluate the in vivo disintegration behavior of tablets and capsules of a bile acid sequestrant, DMP 504, in beagle dogs and to assess the significance of the in vitro disintegration of the dosage forms on subsequent in vivo behavior in order to draw possible in vitro-in vivo correlations. Tablet and capsule formulations of a bile acid sequestrant, DMP 504, were formulated with samarium oxide and neutron activated to produce radioactive 53Sm to noninvasively evaluate their in vivo behavior in beagle dogs by gamma-scintigraphy. A four-way crossover design was completed (n = 4) in which (a) tablets from two different batches were administered under the fasted condition and manufactured using different lots of drug substance where one batch exhibited relatively faster in vitro disintegration time (30 min) than the other tablet batch, which resulted in slower disintegration (45 min), (b) a capsule formulation was administered to fasted beagles, and (c) the tablet having slower in vitro disintegration was also administered in the fed state, and its in vivo disintegration was compared to that observed in the fasted state. Tablets manufactured using a lot of DMP 504 having relatively fast in vitro disintegration (approximately 30 min) resulted in relatively rapid in vivo disintegration time (15 min) in the fasted condition. This in vivo disintegration time was comparable to the in vivo disintegration of the capsules (17 min) even though the in vitro capsule disintegration time was considerably faster (2 min). Tablets prepared using a drug substance that provided a longer in vitro disintegration time (approximately 45 min) resulted in a slower in vivo disintegration (63 min). There was no difference observed in the in vivo disintegration behavior in fasted and fed dogs for the tablets that provided slower in vitro disintegration. In vivo disintegration of tablets of the bile acid sequestrant DMP 504 correlated with in vitro disintegration times. Gamma-Scintigraphy continues to be a good tool to use during early stages of product development to investigate in vivo performance of dosage forms. The results of this study provided evidence that the physical chemical specifications of the drug substance may not always be indicative of in vitro or in vivo performance of tablet dosage form, even when formulation and process are not changed.

In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

PubMed

Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

2008-04-01

The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not adequate to establish similar disintegration characteristics.

New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach.

PubMed

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

2017-10-01

The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X 1 ), impeller speed (X 2 ), wet massing time (X 3 ), and water addition rate (X 4 ) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p < .05) effect on granules and tablets characteristics. However, the water amount had the most pronounced effect as indicated by its higher parameter estimate. On the other hand, water addition rate showed a minimal impact on granules and tablets properties. In conclusion, water amount, impeller speed, and wet massing time could be considered as critical process variables. Thus, understanding the relationship between these variables and quality attributes of granules and corresponding tablets provides the basis for adjusting granulation variables in order to optimize product performance.

Assessment of Tablet Surface Hardness by Laser Ablation and Its Correlation With the Erosion Tendency of Core Tablets.

PubMed

Narang, Ajit S; Breckenridge, Lydia; Guo, Hang; Wang, Jennifer; Wolf, Abraham Avi; Desai, Divyakant; Varia, Sailesh; Badawy, Sherif

2017-01-01

Surface erosion of uncoated tablets results in processing problems such as dusting and defects during coating and is governed by the strength of particle bonding on tablet surface. In this study, the correlation between dusting tendency of tablets in a coating pan with friability and laser ablation surface hardness was assessed using tablets containing different concentrations of magnesium stearate and tartaric acid. Surface erosion propensity of different batches was evaluated by assessing their dusting tendency in the coating pan. In addition, all tablets were analyzed for crushing strength, friability, modified friability test using baffles in the friability apparatus, and weight loss after laser ablation. Tablets with similar crushing strength showed differences in their surface erosion and dusting tendency when rotated in a coating pan. These differences did not correlate well with tablet crushing strength or friability but did show reasonably good correlation with mass loss after laser ablation. These results suggest that tablet surface mass loss by laser ablation can be used as a minipiloting (small-scale) tool to assess tablet surface properties during early stages of drug product development to assess the risk of potential large-scale manufacturing issues. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Tablet disintegration studied by high-resolution real-time magnetic resonance imaging.

PubMed

Quodbach, Julian; Moussavi, Amir; Tammer, Roland; Frahm, Jens; Kleinebudde, Peter

2014-01-01

The present work employs recent advances in high-resolution real-time magnetic resonance imaging (MRI) to investigate the disintegration process of tablets containing disintegrants. A temporal resolution of 75 ms and a spatial resolution of 80 × 80 µm with a section thickness of only 600 µm were achieved. The histograms of MRI videos were quantitatively analyzed with MATLAB. The mechanisms of action of six commercially available disintegrants, the influence of relative tablet density, and the impact of disintegrant concentration were examined. Crospovidone seems to be the only disintegrant acting by a shape memory effect, whereas the others mainly swell. A higher relative density of tablets containing croscarmellose sodium leads to a more even distribution of water within the tablet matrix but hardly impacts the disintegration kinetics. Increasing the polacrilin potassium disintegrant concentration leads to a quicker and more thorough disintegration process. Real-time MRI emerges as valuable tool to visualize and investigate the process of tablet disintegration.

Development of a novel and simple method to evaluate disintegration of rapidly disintegrating tablets.

PubMed

Hoashi, Yohei; Tozuka, Yuichi; Takeuchi, Hirofumi

2013-01-01

The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions from those of an actual oral cavity. Six RDTs prepared in our laboratory and 5 types of commercial RDTs were used as model formulations. Using our original apparatus, a good correlation was observed between in vivo and in vitro disintegration times by adjusting the height from which the solution was dropped to 8 cm and the weight of the load to 10 or 20 g. Properties of RDTs, such as the pattern of their disintegrating process, can be assessed by verifying the load. These findings confirmed that our proposed method for an in vitro disintegration test apparatus is an excellent one for estimating disintegration time and the disintegration profile of RDTs.

Prediction of oral disintegration time of fast disintegrating tablets using texture analyzer and computational optimization.

PubMed

Szakonyi, G; Zelkó, R

2013-05-20

One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterising the disintegration properties of tablets in opaque media using texture analysis.

PubMed

Scheuerle, Rebekah L; Gerrard, Stephen E; Kendall, Richard A; Tuleu, Catherine; Slater, Nigel K H; Mahbubani, Krishnaa T

2015-01-01

Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. This study has explored an application of texture analysis disintegration testing, a non-visual, quantitative means of determining tablet disintegration end point, by analysing the disintegration behaviour of two tablet formulations in opaque media. In this study, the disintegration behaviour of one tablet formulation manufactured in-house, and Sybedia Flashtab placebo tablets in water, bovine, and human milk were characterised. A novel method is presented to characterise the disintegration process and to quantify the disintegration end points of the tablets in various media using load data generated by a texture analyser probe. The disintegration times in the different media were found to be statistically different (P<0.0001) from one another for both tablet formulations using one-way ANOVA. Using the Tukey post-hoc test, the Sybedia Flashtab placebo tablets were found not to have statistically significant disintegration times from each other in human versus bovine milk (adjusted P value 0.1685). Copyright © 2015 Elsevier B.V. All rights reserved.

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.

[Stability of disintegration in health food].

PubMed

Ma, Lan; Zhao, Xin; Zhou, Shuang; Yang, Dajin

2012-11-01

To study the change of disintegration of different formulation samples which stored in the artificial climate box or room temperature and provide the technical support for health food monitoring. According to the method of Chinese Pharmacopoeia and British Pharmacopoeia. Appendix XII A. Disintegration 2010. Disintegration of the non-accelerate, accelerated after 1, 2 and 3 months samples were determined by the disintegrator, respectively. Sample properties, the ingredients of the samples, the proportions of the capsule and treatment methods have some effect on the stability of the disintegration. The disintegration time of health food will be changed particularly after they were accelerated under the condition of (38 +/- 1) degrees C/75% RH. Especially the disintegration time of soft capsules were significantly prolonged. The composition and properties of samples were the main factors that affected the disintegration.

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Assessment of disintegration of rapidly disintegrating tablets by a visiometric liquid jet-mediated disintegration apparatus.

PubMed

Desai, Parind M; Liew, Celine V; Heng, Paul W S

2013-02-14

The aim of this study was to develop a responsive disintegration test apparatus that is particularly suitable for rapidly disintegrating tablets (RDTs). The designed RDT disintegration apparatus consisted of disintegration compartment, stereomicroscope and high speed video camera. Computational fluid dynamics (CFD) was used to simulate 3 different designs of the compartment and to predict velocity and pressure patterns inside the compartment. The CFD preprocessor established the compartment models and the CFD solver determined the numerical solutions of the governing equations that described disintegration medium flow. Simulation was validated by good agreement between CFD and experimental results. Based on the results, the most suitable disintegration compartment was selected. Six types of commercial RDTs were used and disintegration times of these tablets were determined using the designed RDT disintegration apparatus and the USP disintegration apparatus. The results obtained using the designed apparatus correlated well to those obtained by the USP apparatus. Thus, the applied CFD approach had the potential to predict the fluid hydrodynamics for the design of optimal disintegration apparatus. The designed visiometric liquid jet-mediated disintegration apparatus for RDT provided efficient and precise determination of very short disintegration times of rapidly disintegrating dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of disintegration testing of different fast dissolving tablets using the texture analyzer.

PubMed

el-Arini, Silvia Kocova; Clas, Sophie-Dorothée

2002-01-01

The in vitro disintegration behavior of fast dissolving systems manufactured by the main commercialized technologies was studied using the texture analyzer (TA) instrument. Quantitative parameters were employed to characterize the effect of the major test variables on the disintegration profiles. The average disintegration profiles of the products were compared using the test conditions that minimized these effects and at the same time mimicked the in vivo situation in the patient's mouth. The differences in the disintegration mechanisms of the fast dissolving systems were reflected in the shape of their disintegration profiles and in the parameters derived from the profiles. The differences were explained in relation to the technology and/or formulation characteristics involved in the manufacture of each product. The in vitro disintegration times obtained under the simulated in vivo conditions were correlated with the reported in vivo disintegration times.

Performance of tablet disintegrants: impact of storage conditions and relative tablet density.

PubMed

Quodbach, Julian; Kleinebudde, Peter

2015-01-01

Tablet disintegration can be influenced by several parameters, such as storage conditions, type and amount of disintegrant, and relative tablet density. Even though these parameters have been mentioned in the literature, the understanding of the disintegration process is limited. In this study, water uptake and force development of disintegrating tablets are analyzed, as they reveal underlying processes and interactions. Measurements were performed on dibasic calcium phosphate tablets containing seven different disintegrants stored at different relative humidities (5-97%), and on tablets containing disintegrants with different mechanisms of action (swelling and shape recovery), compressed to different relative densities. Disintegration times of tablets containing sodium starch glycolate are affected most by storage conditions, which is displayed in decreased water uptake and force development kinetics. Disintegration times of tablets with a swelling disintegrant are only marginally affected by relative tablet density, whereas the shape recovery disintegrant requires high relative densities for quick disintegration. The influence of relative tablet density on the kinetics of water uptake and force development greatly depends on the mechanism of action. Acquired data allows a detailed analysis of the influence of storage conditions and mechanisms of action on disintegration behavior.

A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.

PubMed

Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter

2016-08-01

A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Dissolution Studies of Papaverine Hydrochloride from Tablets in Three Pharmacopoeia Apparatuses.

PubMed

Polski, Andrzej; Kasperek, Regina; Rogowska, Magdalena; Iwaniak, Karol; Sobòtka-Polska, Karolina; Poleszak, Ewa

2015-01-01

In tablet production, the most important aspects are the physical properties of the tablets and their dissolution studies, which can be performed in four pharmacopoeial apparatuses. There are differences between them in construction and action, so differences in the results obtained are possible. The aim of the study was to compare the release of a model drug substance (papaverine hydrochloride) from tablets in three pharmacopoeial dissolution apparatus: a basket, a paddle (closed system) and flow-through cell (open system). The one series of tablets were produced by direct compression in a tablet press. The physical properties of the tablets (weight and size uniformity test, friability and hardness tests, disintegration time test), drug content and the release study of papaverine hydrochloride from tablets were studied in three dissolution apparatuses. The content of the active substance was studied spectrophotometrically. All tablets met the pharmacopoeic requirements. Over 80% of the model substance released from the tablets after 14 min in flow through the cell apparatus, while in the basket and paddle apparatuses after about 7 min 30 sec. After 20 min, the amount of the substance released in all apparatuses was over 90%. The release profiles of the drug substance in paddle and basket apparatuses were similar, while in the flow-through cell apparatus it was slightly slower. When the study conditions and composition of the tablets are the same, the release profile of the drug can be affected by the type of dissolution apparatus.

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.

Real-time monitoring of disintegration activity of catalytic core domain of HIV-1 integrase using molecular beacon.

PubMed

Zhang, Da-wei; Zhao, Ming-ming; He, Hong-qiu; Guo, Shun-xing

2013-09-15

HIV-1 integrase, an essential enzyme for retroviral replication, is a validated target for anti-HIV therapy development. The catalytic core domain of integrase (IN-CCD) is capable of catalyzing disintegration reaction. In this work, a hairpin-shaped disintegration substrate was designed and validated by enzyme-linked immunosorbent assay; a molecular beacon-based assay was developed for disintegration reaction of IN-CCD. Results showed that the disintegration substrate could be recognized and catalyzed by IN-CCD, and the disintegration reaction can be monitored according to the increase of fluorescent signal. The assay can be applied to real-time detection of disintegration with advantages of simplicity, high sensitivity, and excellent specificity. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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.

A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

PubMed

Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

2015-11-01

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Comparative study on novel test systems to determine disintegration time of orodispersible films.

PubMed

Preis, Maren; Gronkowsky, Dorothee; Grytzan, Dominik; Breitkreutz, Jörg

2014-08-01

Orodispersible films (ODFs) are a promising innovative dosage form enabling drug administration without the need for water and minimizing danger of aspiration due to their fast disintegration in small amounts of liquid. This study focuses on the development of a disintegration test system for ODFs. Two systems were developed and investigated: one provides an electronic end-point, and the other shows a transferable setup of the existing disintegration tester for orodispersible tablets. Different ODF preparations were investigated to determine the suitability of the disintegration test systems. The use of different test media and the impact of different storage conditions of ODFs on their disintegration time were additionally investigated. The experiments showed acceptable reproducibility (low deviations within sample replicates due to a clear determination of the measurement end-point). High temperatures and high humidity affected some of the investigated ODFs, resulting in higher disintegration time or even no disintegration within the tested time period. The methods provided clear end-point detection and were applicable for different types of ODFs. By the modification of a conventional test system to enable application for films, a standard method could be presented to ensure uniformity in current quality control settings. © 2014 Royal Pharmaceutical Society.

75 FR 17147 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

...] International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts... Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 9: Tablet Friability General Chapter... results of the ICH Q4B evaluation of the Tablet Friability General Chapter harmonized text from each of...

Disintegration of Nannochloropsis sp. cells in an improved turbine bead mill.

PubMed

Pan, Zhidong; Huang, Ying; Wang, Yanmin; Wu, Zhiwei

2017-12-01

The Nannochloropsis sp. cells in aqueous solution were disintegrated in an improved bead mill with turbine agitator. The disintegration rates of cell samples disrupted under various operating parameters (i.e., circumferential speed, bead size, disintegration time, and cell concentration) were analyzed. An experimental strategy to optimize the parameters affecting the cell disintegration process was proposed. The results show that Nannochloropsis sp. cells can be effectively disintegrated in the turbine stirred bead mill under the optimum condition (i.e., circumferential speed of 2.3m/s, concentration of 15vol.%, disintegration time of 40min and bead size of 0.3-0.4mm). The disintegration mechanism was discussed via the selection and breakage functions from population balance modelling. It is revealed that the impact and compression effects of stirring beads are more effective for the disruption of coarser fraction of cells, and the shear effect dominates the production of finer fractions of disintegrated cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

PubMed

Liu, Yali; Li, Peng; Qian, Rong; Sun, Tianyu; Fang, Fangzhi; Wang, Zonghua; Ke, Xue; Xu, Bohui

2018-08-01

The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X 1 ) mannitol/microcrystalline cellulose ratio, (X 2 ) the amount of low-substituted hydroxypropylcellulose and (X 3 ) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.

Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets.

PubMed

Zaheer, Kamran; Langguth, Peter

2018-03-01

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force - time curves revealed a direct relation of maximum disintegration force (F max ) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.

The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs).

PubMed

Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

2015-09-01

Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800-900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT's disintegration time determination is eligible and scientifically justified.

Pharmaceutics, Drug Delivery and Pharmaceutical Technology: A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

PubMed

Low, Ariana; Kok, Si Ling; Khong, Yuetmei; Chan, Sui Yung; Gokhale, Rajeev

2015-11-01

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3893-3903, 2015. Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Process analytical technology to understand the disintegration behavior of alendronate sodium tablets.

PubMed

Xu, Xiaoming; Gupta, Abhay; Sayeed, Vilayat A; Khan, Mansoor A

2013-05-01

Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products. Copyright © 2013 Wiley Periodicals, Inc.

Optimization of thermo-alkaline disintegration of sewage sludge for enhanced biogas yield.

PubMed

Shehu, Muhammad Sani; Abdul Manan, Zainuddin; Alwi, Sharifah Rafidah Wan

2012-06-01

Optimization of thermo-alkaline disintegration of sewage sludge for enhanced biogas yield was carried out using response surface methodology (RSM) and Box-Behnken design of experiment. The individual linear and quadratic effects as well as the interactive effects of temperature, NaOH concentration and time on the degree of disintegration were investigated. The optimum degree of disintegration achieved was 61.45% at 88.50 °C, 2.29 M NaOH (24.23%w/w total solids) and 21 min retention time. Linear and quadratic effects of temperature are most significant in affecting the degree of disintegration. The coefficient of determination (R(2)) of 99.5% confirms that the model used in predicting the degree of disintegration process has a very good fitness with the experimental variables. The disintegrated sludge increased the biogas yield by 36%v/v compared to non-disintegrated sludge. The RSM with Box-Behnken design is an effective tool in predicting the optimum degree of disintegration of sewage sludge for increased biogas yield. Copyright © 2012 Elsevier Ltd. All rights reserved.

Applicability of two automated disintegration apparatuses for rapidly disintegrating (mini)tablets.

PubMed

Sieber, Daniel; Lazzari, Alessia; Quodbach, Julian; Pein, Miriam

2017-03-01

Orally disintegrating (mini)tablets (OD(M)Ts) are of interest in the field of pharmaceutics. Their orodispersible character is defined by the disintegration time, which is measured with a basket apparatus according to the European Pharmacopoeia. This method, however, lacks applicability for ODTs and especially ODMTs. New disintegration apparatuses have been described in literature, but a qualification to assess the applicability has not been described. A qualification procedure for two automated disintegration apparatuses, OD-mate and Hermes apparatus, is introduced. Aspects of the operational qualification as well as precision and accuracy regarding a performance qualification were evaluated for both apparatuses analog to the ICH guideline Q2. While the OQ study is performed separately for each apparatus, accuracy and precision were performed following the same protocol for both testers. Small RSDs (16.9% OD-mate; 15.2% Hermes compared to 32.3% for the pharmacopeial method) were found despite very fast disintegration times (1.5 s for both apparatuses). By comparing these RSDs to practical examples, the authors propose threshold values for repeatability depending on the mean disintegration time. Obtained results from the qualification were used to assess the applicability of both apparatuses.

Investigation of the performance of the disintegration test for dietary supplements.

PubMed

Almukainzi, May; Salehi, Mahnor; Araci Bou-Chacra, Nadia; Löbenberg, Raimar

2010-12-01

The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, <701> and <2040>. Two beakers complying with the harmonized specifications were used, one with a volume of 1,000 mL and one with a 1,500-mL volume. The disintegration data were analyzed using ANOVA for the following factors: beaker size, equipment (App A and B) and condition (with/without disk). Two tablet products were not sensitive to any changes in the test conditions or equipment configurations. One product was only partially sensitive to the test conditions. The other products showed impact on the disintegration time for all test conditions. The results revealed that these tablet products might pass or fail current USP disintegration requirements depending on the equipment configuration. Similar results were obtained for the two investigated capsule formulations. One product might fail current USP disintegration requirements if the large beaker was used, but might pass the disintegration requirements when the small beaker was used. Hydroxy propyl methyl cellulose capsules were mostly influenced if sodium instead of a potassium buffer was used as the immersion medium. The results demonstrate that the current harmonized ICH specifications for the disintegration test are insufficient to make the disintegration test into reliable test for dietary supplements.

[Preparation and quality control of pyridostigmine bromide orally disintegrating tablet].

PubMed

Zhang, Li; Tan, Qun-you; Cheng, Xun-guan; Wang, Hong; Hu, Ni-ni; Zhang, Jing-qing

2012-05-01

To prepare orally disintegrating tablets containing pyridostigmine bromide and optimize formulations. Solid dispersion was prepared using solvent evaporation-deposition method. The formulation was optimized by central composite design-response surface methodology (RSM plus CCD) with disintegration time as a reference parameter. The orally disintegrating tablets showed integrity and were smooth with desirable taste and feel in mouth. The disintegration time was less than 30 s. The cumulative drug dissolution was around 8.5% (around 2.5 mg which was less than bitterness threshold of pyridostigmine bromide of 3 mg) within 5 min in water while the cumulative drug dissolution was higher than 95% within 2 min in 0.1 N HCl. The orally disintegrating tablets are reasonable in formulation, feasible in technology and patient-friendly.

The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs)

PubMed Central

Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

2015-01-01

Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800–900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p < 0.001), and 0.9907 (p < 0.001) respectively. The pharmacopoeial method correlated with the in vivo data much worse (r = 0.8925, p < 0.05). These results have shown that development of novel biorelevant methods of ODT’s disintegration time determination is eligible and scientifically justified. PMID:27134547

Use of a continuous twin screw granulation and drying system during formulation development and process optimization.

PubMed

Vercruysse, J; Peeters, E; Fonteyne, M; Cappuyns, P; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

2015-01-01

Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and tablet quality attributes were obtained during the start-up phase of the 1h run. For the single cell runs, granule and tablet properties were comparable with results obtained during the second part of the 1h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for tablet quality obtained during continuous production using the ConsiGma™-25 system. Copyright © 2014 Elsevier B.V. All rights reserved.

Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates

PubMed Central

Olszynski, Wojciech P.; Adachi, Jonathan D.; Davison, K. Shawn

2014-01-01

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P < 0.05) faster for Apo-alendronate (26 ± 5.6 seconds) and Novo-alendronate (13 ± 1.1 seconds) as compared to brand alendronate (147 ± 50.5 seconds), brand alendronate plus vitamin D (378 ± 60.5 seconds), or brand risedronate (101 ± 20.6 seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies. PMID:25349772

Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates.

PubMed

Olszynski, Wojciech P; Adachi, Jonathan D; Davison, K Shawn

2014-01-01

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P < 0.05) faster for Apo-alendronate (26 ± 5.6 seconds) and Novo-alendronate (13 ± 1.1 seconds) as compared to brand alendronate (147 ± 50.5 seconds), brand alendronate plus vitamin D (378 ± 60.5 seconds), or brand risedronate (101 ± 20.6 seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.

Consumer vinegar test for determining calcium disintegration.

PubMed

Mason, N A; Patel, J D; Dressman, J B; Shimp, L A

1992-09-01

A consumer test and standardized methods were compared for measuring the disintegration of calcium tablets, and the disintegration results were compared with results of dissolution testing to determine the ability of the consumer test of disintegration to predict bioavailability of calcium. Disintegration of 17 calcium supplement products, in tablet form, was studied in Simulated Gastric Fluid Test Solution, USP, without pepsin (GF), in distilled water, and in white distilled vinegar. For disintegration testing with GF and with distilled water, six tablets of each product were placed in an apparatus and immersed in the solution at 37 degrees C for 60 minutes. Six tablets of each product were tested in 200 mL of vinegar at room temperature for 30 minutes. Disintegration was determined by visual observation. Seven products were tested for dissolution in GF or water. Three samples of each product were tested at intervals over 120 minutes for calcium content. Results of testing with an ion-selective electrode were converted to milligrams and compared with the calcium content of the tablets (as claimed on the package label). The mean disintegration times of various calcium products in vinegar ranged from 1.8 to greater than 30 minutes. The mean time in distilled water and GF ranged from 1.6 to greater than 60 minutes and from 1.0 to greater than 60 minutes, respectively. Results were in agreement in 87% to 93% of cases between the consumer vinegar test and the standardized disintegration test methods, a significant correlation. No correlation was found between disintegration time and the extent of dissolution. The disintegration and dissolution of commercially available calcium tablets was highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of Loperamide Dissolution Rate by Liquisolid Compact Technique.

PubMed

Venkateswarlu, Kambham; Preethi, Jami Komala; Chandrasekhar, Kothapalli Bonnoth

2016-09-01

Purpose: The aim of present study was to improve the dissolution rate of poorly soluble drug Loperamide (LPM) by liquisolid compact technique. Methods: Liquisolid compacts of LPM were prepared using Propylene glycol (PG) as a solvent, Avicel pH 102 as carrier, Aerosil as coating material and Sodium Starch Glycolate (SSG) as superdisintegrant. Interactions between the drug and excipients were examined by Fourier Transform Infrared (FTIR) spectroscopy. The dissolution studies for LPM liquisolid formulation, marketed product and pure drug were carried out in pH 1.2 HCl buffer as dissolution media. Results: Results confirmed the absence of chemical interactions between the drug and excipients. From the solubility studies, it was observed the LPM was highly soluble in PG thereby it was selected as a solvent. The dissolution efficiency of LPM at 15 min was increased from 9.99 % for pure drug and 54.57% for marketed product to 86.81% for the tablets prepared by liquisolid compact technique. Stability studies showed no significant change in percent cumulative drug release, hardness, disintegration time, friability and drug content for 3 months. Conclusion: Formulation F2 showed significant increase in dissolution rate compared to the marketed product at pH 1.2 where LPM is largely absorbed. Around 90% of the drug was released from F2 in 30 min compared to the marketed product and it might be due to the increased wetting and surface area of the particles. Hence, the liquisolid compact technique appears to be a promising approach for improving the dissolution rate of poorly soluble drug.

Review of Disintegrants and the Disintegration Phenomena.

PubMed

Desai, Parind Mahendrakumar; Liew, Celine Valeria; Heng, Paul Wan Sia

2016-09-01

Disintegrant is one of the most important components in a typical tablet dosage form. It is responsible for ensuring the break-up of the tablet matrix upon ingestion. Disintegrants act by different mechanisms, and a number of factors may affect their performance. It is important for formulators to understand how disintegrants function so as to be able to judiciously use disintegrants to develop optimized formulations. If the formulator is required to implement the quality by design paradigm while developing a tablet formulation, it would be important to determine the impact of component ranges and process variations on tablet performance and of particular importance, tablet disintegration. Thus, a better understanding of the mechanisms of disintegrants and the tablet disintegration processes can be critical to product design success. This review aims to provide an overview of tablet disintegrants and the disintegration processes with particular focus on the factors affecting the functionalities of disintegrants. An updated compendium of different techniques employed to evaluate disintegrant action and measure disintegration time is also provided. The objective of this review is to assemble the knowledge about disintegrants and the measurement of tablet disintegratability so that the information provided could be of help to tablet formulation development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

PubMed

Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

2014-01-30

Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. Copyright © 2013 Elsevier B.V. All rights reserved.

Disintegration performance of renal multivitamin supplements.

PubMed

Stamatakis, M K; Meyer-Stout, P J

1999-04-01

Vitamins have traditionally been regulated as dietary supplements and have not been required to meet the same rigorous product quality performance standards as drug products. Impaired product performance, such as failure to disintegrate and/or dissolve in the gastrointestinal tract, could limit the absorption of vitamins. Furthermore, patients with renal disease have been reported to experience a wide range in gastrointestinal pH, which could influence a product's performance. The purpose of this study was to determine the effect of pH on the in vitro disintegration of renal multivitamin supplements. Products were studied using the United States Pharmacopeial Convention standard disintegration apparatus. Products were tested in simulated gastric fluid, neutral fluid, and intestinal fluid. Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within compendial limits. Of 11 products tested, 4 products failed the disintegration study test in all pH conditions. Sixty-four percent of the products showed statistically significant differences in disintegration time (DT) based on pH. As pH increased, time to disintegration increased. The DT of commercially available renal multivitamin supplements was highly variable. Poorest product performance was shown in simulated intestinal fluid. The pH significantly affected in vitro disintegration in greater than half the products tested. How this affects dissolution and in vivo performance has yet to be studied.

21 CFR 320.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., where applicable, content uniformity, disintegration times, and/or dissolution rates. (d) Pharmaceutical..., disintegration times and/or dissolution rates. (e) Bioequivalence means the absence of a significant difference...

Dissolution testing of orally disintegrating tablets.

PubMed

Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

2012-07-01

For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

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.

Disintegration of highly soluble immediate release tablets: a surrogate for dissolution.

PubMed

Gupta, Abhay; Hunt, Robert L; Shah, Rakhi B; Sayeed, Vilayat A; Khan, Mansoor A

2009-01-01

The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.

Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.

PubMed

Liew, Kai Bin; Tan, Yvonne Tze Fung; Peh, Kok Khiang

2015-04-01

Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.

Fabrication and optimization of fast disintegrating tablets employing interpolymeric chitosan-alginate complex and chitin as novel superdisintegrants.

PubMed

Goel, Honey; Tiwary, Ashok K; Rana, Vikas

2011-01-01

The objective of the present work was to optimize the formulation of fast disintegrating tablets (FDTs) of ondansetron HCl containing novel superdisintegrants, possessing sufficient mechanical strength and disintegration time comparable to those containing crospovidone or croscarmellose sodium. The FDTs were formulated using a novel superdisintegrant (chitosan-alginate (1:1) interpolymer complex and chitin) to achieve a sweet tasting disintegrating system. The results revealed that chitin (5-20%) increased the porosity and decreased the DT of tablets. At higher concentrations chitin maintained tablet porosity even at 5.5 kg crushing strength. Ondansetron HCl was found to antagonize the wicking action of glycine. Further, evaluation of the mechanism of disintegration revealed that glycine transported the aqueous medium to different parts of the tablets while the chitosan-alginate complex swelled up due to transfer of moisture from glycine. This phenomenon resulted in breakage of the tablet within seconds. For preparing optimized FDTs, the reduced model equations generated from Box-Behnken design (BBD) were solved after substituting the known disintegration time of FDTs containing superdisintegrants in the reduced model equations. The results suggested that excipient system under investigation not only improved the disintegration time but also made it possible to prepare FDTs with higher crushing strength as compared to tablets containing known superdisintegrants.

Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach.

PubMed

Rajkumar, Arthi D; Reynolds, Gavin K; Wilson, David; Wren, Stephen; Hounslow, Michael J; Salman, Agba D

2016-09-01

Tablet disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the tablet will break up in vivo and that active drug will be available for absorption. Variations in tablet properties cause variation in disintegration behaviour. While the standardised pharmacopeial disintegration test can show differences in the speed of disintegration of different tablets, it does not give any mechanistic information about the underlying cause of the difference. With quantifiable disintegration data, and consequently an improved understanding into tablet disintegration, a more knowledge-based approach could be applied to the research and development of future tablet formulations. The aim of the present research was to introduce an alternative method which will enable a better understanding of tablet disintegration using a particle imaging approach. A purpose-built flow cell was employed capable of online observation of tablet disintegration, which can provide information about the changing tablet dimensions and the particles released with time. This additional information can improve the understanding of how different materials and process parameters affect tablet disintegration. Standard USP analysis was also carried out to evaluate and determine whether the flow cell method can suitably differentiate the disintegration behaviour of tablets produced using different processing parameters. Placebo tablets were produced with varying ratios of insoluble and soluble filler (mannitol and MCC, respectively) so that the effect of variation in the formulation can be investigated. To determine the effect of the stress applied during granulation and tableting on tablet disintegration behaviour, analysis was carried out on tablets produced using granular material compressed at 20 or 50bar, where a tableting load of either 15 or 25kN was used. By doing this the tablet disintegration was examined in terms of the tablet porosity by monitoring the tablet area and particle release. It was found that when 20 and 50bar roller compaction pressure was used the USP analysis showed almost identical disintegration times for the consequent tablets. With the flow cell method a greater tablet swelling was observed for the lower pressure followed by steady tablet erosion. Additionally, more particles were released during disintegration due to the smaller granule size distribution within the tablet. When a higher tableting pressure was applied the tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower tablet erosion and particle release were also observed, largely due to the tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the tablet porosity affects the tablet disintegration, whereby a more porous tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and tableting pressure used. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of palatability of 10 commercial amlodipine orally disintegrating tablets by gustatory sensation testing, OD-mate as a new disintegration apparatus and the artificial taste sensor.

PubMed

Uchida, Takahiro; Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Furuno, Hiroyuki; Teraoka, Makoto; Ikezaki, Hidekazu

2013-09-01

The purpose of this study was to evaluate and compare the palatability of 10 formulations (the original manufacturer's formulation and nine generics) of amlodipine orally disintegrating tablets (ODTs) by means of human gustatory sensation testing, disintegration/dissolution testing and the evaluation of bitterness intensity using a taste sensor. Initially, the palatability, dissolution and bitterness intensity of the ODTs were evaluated in gustatory sensation tests. Second, the disintegration times of the ODTs were measured using the OD-mate, a newly developed apparatus for measuring the disintegration of ODTs, and lastly, the bitterness intensities were evaluated using an artificial taste sensor. Using factor analysis, the factors most affecting the palatability of amlodipine ODTs were found to be disintegration and taste. There was high correlation between the disintegration times of the 10 amlodipine ODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of amlodipine ODTs 10, 20 and 30 s after starting the conventional brief dissolution test and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. The OD-mate and the taste sensor may be useful for predicting the disintegration and bitterness intensity of amlodipine ODTs in the mouth. © 2013 Royal Pharmaceutical Society.

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.

Evaluation of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera.

PubMed

Morita, Yutaka; Tsushima, Yuki; Yasui, Masanobu; Termoz, Ryoji; Ajioka, Junko; Takayama, Kozo

2002-09-01

Many kinds of rapidly disintegrating or oral disintegrating tablets (RDT) have been developed to improve the ease of tablet administration, especially for elderly and pediatric patients. In these cases, knowledge regarding disintegration behavior appears important with respect to the development of such a novel tablet. Ordinary disintegration testing, such as the Japanese Pharmacopoeia (JP) method, faces limitations with respect to the evaluation of rapid disintegration due to strong agitation. Therefore, we have developed a novel apparatus and method to determine the dissolution of the RDT. The novel device consists of a disintegrating bath and CCD camera interfaced with a personal computer equipped with motion capture and image analysis software. A newly developed RDT containing various types of binder was evaluated with this protocol. In this method, disintegration occurs in a mildly agitated medium, which allows differentiation of minor distinctions among RDTs of different formulations. Simultaneously, we were also able to detect qualitative information, i.e., morphological changes in the tablet during disintegration. This method is useful for the evaluation of the disintegration of RDT during pharmaceutical development, and also for quality control during production.

The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement.

PubMed

Zen, Nur Izzati Mohamad; Abd Gani, Siti Salwa; Shamsudin, Rosnah; Masoumi, Hamid Reza Fard

2015-01-01

The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets' hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets' hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin.

The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement

PubMed Central

Mohamad Zen, Nur Izzati; Shamsudin, Rosnah

2015-01-01

The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets' hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets' hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin. PMID:26171418

Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation.

PubMed

Surampalli, Gurunath; Nanjwade, Basavaraj K; Patil, P A; Chilla, Rakesh

2016-09-01

The aim of this study was to develop a novel tablet formulation of amorphous candesartan cilexetil (CAN) solid dispersion involving effective P-gp inhibition for optimal drug delivery by direct compression (DC) method. To accomplish DC, formulation blends were evaluated for micromeritic properties. The Carr index, Hausner ratio, flow rate and cotangent of the angle α were determined. The tablets with and without naringin prepared by DC technique were evaluated for average weight, hardness, disintegration time and friability assessments. The drug release profiles were determined to study the dissolution kinetics. In vivo pharmacokinetic studies were conducted in rabbits. Accelerated stability studies were performed for tablets at 40 ± 2 °C/75% RH ± 5% for 6 months. FTIR studies confirmed no discoloration, liquefaction and physical interaction between naringin and drug. The results indicated that tablets prepared from naringin presented a dramatic release (82%) in 30 min with a similarity factor (76.18), which is most likely due to the amorphous nature of drug and the higher micromeritic properties of blends. Our findings noticed 1.7-fold increase in oral bioavailability of tablet prepared from naringin with mean C max and AUC 0-12 h values as 35.81 ± 0.13 μg/mL and 0.14 ± 0.09 μg h/mL, respectively. The tablets with and without naringin prepared by DC technique were physically and chemically stable under accelerated stability conditions upon storage for 6 months. These results are attractive for further development of an oral tablet formulation of CAN through P-gp inhibition using naringin, a natural flavonoid as a pharmaceutical excipient.

Formulation, characterization and physicochemical evaluation of potassium citrate effervescent tablets.

PubMed

Aslani, Abolfazl; Fattahi, Fatemeh

2013-01-01

The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon) and (strawberry - raspberry) had good acceptability. The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.

Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

PubMed Central

Aslani, Abolfazl; Fattahi, Fatemeh

2013-01-01

Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon) and (strawberry - raspberry) had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates. PMID:24312839

[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.

[A study of the properties of compacts from a mixed dry binder on the base of alpha-lactose monohydrate and microcrystalline cellulose].

PubMed

Muzíková, J; Páleník, L

2005-05-01

The paper studies the tensile strength and disintegration time of compacts from the mixed dry binder MicroceLac 100. Tensile strength and disintegration time of tablets were tested in connection with the following factors: compression force, compression rate, addition of magnesium stearate, addition of ascorbic acid, the model active principle. The compression forces employed were 5, 6, and 7 kN, compression rates, 20 and 40 mm/min, stearate concentration 0, 0.4, and 0.8%, ascorbic acid concentration, 25 and 50%. With increasing addition of the stearate, the strength of compacts from MicroceLacu 100 was decreased for both compression rates, but with a higher rate, in a concentration of 0.4%, the decrease in strength was more marked. Disintegration time was increased with compression force and the addition of the stearate, but in all cases it was very short. Increased addition of ascorbic acid further intensified the decrease in the strength of compacts and decreased the disintegration time and the effect of the stearate on it. Disintegration time of compacts with ascorbic acid in a concentration of 50% did not increase with compression force.

Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry.

PubMed

Corá, Luciana A; Romeiro, Fernando G; Paixão, Fabiano C; Américo, Madileine F; Oliveira, Ricardo B; Baffa, Oswaldo; Miranda, José Ricardo A

2006-08-01

To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t50) was quantified from 50% increase of pixels in the imaging area. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t50) calculated for in vitro was 25+/-5 min and for in vivo was 13+/-5 min. In vivo also were determined mean values for GRT (55+/-19 min), SITT (185+/-82 min) and OCTT (240+/-88 min). AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

In situ, real time observation of the disintegration of paracetamol tablets in aqueous solution by magnetic resonance imaging.

PubMed

Tritt-Goc, Jadwiga; Kowalczuk, Joanna

2002-05-01

The disintegration behavior of paracetamol tablets was studied by magnetic resonance imaging (MRI) using the Snapshot FLASH method. The total time of the single experiment is 425 ms and allows the study of the disintegration process in real time. The study was carried out in vitro under acidic gastric pH conditions and may help to predict the behavior of paracetamol tablets in the stomach after oral administration. It was shown that in spite of identical conditions, the disintegration of the tablets under study was different. The distribution of protons of 4-(N-acetyl)aminophenol within the paracetamol tablet was shown to be homogeneous. The study was carried out in a non-destructive way by the SPI MRI method.

Modes of Disintegration of Solid Foods in Simulated Gastric Environment

PubMed Central

Kong, Fanbin

2009-01-01

A model stomach system was used to investigate disintegration of various foods in simulated gastric environment. Food disintegration modes and typical disintegration profiles are summarized in this paper. Mechanisms contributing to the disintegration kinetics of different foods were investigated as related to acidity, temperature, and enzymatic effect on the texture and changes in microstructure. Food disintegration was dominated by either fragmentation or erosion, depending on the physical forces acting on food and the cohesive force within the food matrix. The internal cohesive forces changed during digestion as a result of water penetration and acidic and enzymatic hydrolysis. When erosion was dominant, the disintegration data (weight retention vs. disintegration time) may be expressed with exponential, sigmoidal, and delayed-sigmoidal profiles. The different profiles are the result of competition among the rates of water absorption, texture softening, and erosion. A linear-exponential equation was used to describe the different disintegration curves with good fit. Acidity and temperature of gastric juice showed a synergistic effect on carrot softening, while pepsin was the key factor in disintegrating high-protein foods. A study of the change of carrot microstructure during digestion indicated that degradation of the pectin and cell wall was responsible for texture softening that contributed to the sigmoidal profile of carrot disintegration. PMID:20401314

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

PubMed

Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal relief from breakthrough pain is best attained by administering analgesics with dissolution times and bioavailabilities that closely match the onset and duration of breakthrough pain. The objective of this study was to assess complete disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

The influence of granulation on super disintegrant performance.

PubMed

Zhao, Na; Augsburger, Larry L

2006-02-01

The purpose of this study is to identify the causes of efficiency loss of super disintegrants following granulation or reworking. Two processes, precompression and prewetting, were proposed to simulate the processes during dry and wet granulation, respectively. The disintegration efficiency of the resulting disintegrant granules was tested in model formulations composed of dicalcium phosphate and lactose with the unprocessed disintegrants as controls. No significant difference was shown in the intrinsic swelling and the water uptake abilities of all super disintegrants following dry granulation. However, a significant decrease was observed for both Primojel and Polyplasdone XL10 in the rate of water being absorbed into the tablet matrix following wet granulation, but not for Ac-Di-Sol. United States Pharmacopeia (USP) disintegration testing without disc revealed a significant increase in disintegration time for tablets formulated with dry granulated Primojel and Polyplasdone XL10 and all wet granulated disintegrants. The increase in particle size following granulation appears to be the cause of the loss in disintegration efficiency. In conclusion, Ac-Di-Sol is less affected by both precompression and prewetting. The efficiency of Primojel and Polyplasdone XL10 is highly dependent on their particle size. Descreasing the particle size tends to increase their efficiency. Due to the size increase following granulation, a higher addition level of super disintegrant is required to ensure fast and uniform disintegration of tablets prepared by granulation.

A new formulation for orally disintegrating tablets using a suspension spray-coating method.

PubMed

Okuda, Y; Irisawa, Y; Okimoto, K; Osawa, T; Yamashita, S

2009-12-01

The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants.

Disintegration rate and properties of active pharmaceutical ingredient particles as determined from the dissolution time profile of a pharmaceutical formulation: an inverse problem.

PubMed

Horkovics-Kovats, Stefan

2014-02-01

Dissolution profile of a finished dosage form (FDF) contains hidden information regarding the disintegration of the form and the particle properties of the active pharmaceutical ingredient. Here, an extraction of this information from the dissolution profile without limitation to sink conditions is provided. In the article, mathematical relationships between the continuously measured dissolution profile of an FDF containing uniform or heterogeneous particles and its disintegration rate are developed. Further, the determinability of the disintegration kinetics and particle properties released from an FDF using the derived recurrent procedure was analyzed. On the basis of the theoretical data sets, it was demonstrated that the introduced analysis of dissolution profiles correctly identifies the disintegration rate of FDF containing multiple particle types. Furthermore, for known disintegration rates, the intrinsic lifetime of particles (time needed for total particle dissolution in infinite volume) released from the FDF and their relative amount can be determined. The extractable information from FDF dissolution time profiles can be utilized in designing of the formulation process, resulting in improved understanding of FDF properties, contributing thus to the implementation of quality by design in the FDF development. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

The effect of superdisintegrants on the properties and dissolution profiles of liquisolid tablets containing rosuvastatin.

PubMed

Vraníková, Barbora; Gajdziok, Jan; Doležel, Petr

2017-03-01

The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time. The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®). LSS were prepared by spraying rosuvastatin solution onto Neusilin® US2 and further processing into tablets. Varying amounts of superdisintegrants were used and the differences among LSS were evaluated. The multiple scatter plot method was used to visualize the relationships within the obtained data. All disintegrants do not showed negative effect on the flow properties of powder blends. The type and concentration of superdisintegrant had an impact on the disintegration time and dissolution profiles of tablets. Tablets with Explotab® showed the longest disintegration time and the smallest amount of released drug. Fastest disintegration and dissolution rate were observed in tablets containing Kollidon® CL-F (≥2.5% w/w). Also tablets with Vivasol® (2.5-4.0% w/w) showed fast disintegration and complete drug release. Kollidon® CL-F and Vivasol® in concentration ≥2.5% are suitable superdisintegrants for LSS with enhanced release of drug.

Systematic dynamic viscoelasticity measurements for chitin nanofibers prepared with various concentrations, disintegration times, acidities, and crystalline structures.

PubMed

Suenaga, Shin; Osada, Mitsumasa

2018-04-17

Dynamic viscoelasticities were measured for chitin nanofiber (ChNF) dispersions prepared with various concentrations, disintegration times, acidities, and crystalline structures. The 0.05 w/v% dispersions of pH neutral ChNFs continuously exhibited elastic behavior. The 0.05 w/v% dispersions of acidified ChNFs, on the other hand, transitioned from a colloidal dispersion to a critical gel and then exhibited elastic behavior with increasing ChNF concentration. A double-logarithmic chart of the concentration vs. the storage modulus was prepared and indicated the fractal dimension and the nanostructure in the dispersion. The results determined that the neutral α- and β-ChNFs were dispersed but showed some remaining aggregations and that the acidified β-ChNFs were completely individualized. In addition, the α-chitin steadily disintegrated with increasing disintegration time, and the aspect ratio of the β-chitin decreased as a result of the exscessive disintegration. The storage moduli of the ChNFs were greater than those of chitin solutions, nanorods, and nanowhiskers with the same solids concentrations. Copyright © 2018 Elsevier B.V. All rights reserved.

Hydrophobic polymers for orodispersible films: a quality by design approach.

PubMed

Borges, Ana Filipa; Silva, Branca M A; Silva, Cláudia; Coelho, Jorge F J; Simões, Sérgio

2016-10-01

To develop orodispersible films (ODF) based on hydrophobic polymers with higher stability to ordinary environmental humidity conditions without compromising their fast disintegration time. A quality by design approach was applied to screen three different formulations each one based on a different hydrophobic polymer: polyvinyl acetate, methacrylate-based copolymer and shellac. The screening formulations were characterized regarding their mechanical properties, residual water content, disintegration time and appearance, in order to find a suitable ODF formulation according to established critical quality attributes. The selected critical process parameters for the selection of appropriate ODF formulations were the percentage of the different excipients and the plasticizer type. Three hydrophobic-based matrices with fast disintegration were developed. These were generically composed by a hydrophobic polymer, a stabilizer, a disintegrant and a plasticizer. It verified that the common components within the three different formulations behave differently depending on the system/chemical environment that they were included. It was shown that it is possible to develop oral films based on hydrophobic polymers with fast disintegration time, good texture and appearance, breaking a paradigm of the ODF research field.

An easy-to-use approach for determining the disintegration ability of disintegrants by analysis of available surface area.

PubMed

Iwao, Yasunori; Tanaka, Shoko; Uchimoto, Takeaki; Noguchi, Shuji; Itai, Shigeru

2013-05-01

With the aim of directly predicting the functionality and mechanism of disintegrants during the disintegration and dissolution of tablets, we investigated an analysis method based on available surface area, which is the surface area of a drug in a formulation in direct contact with the external solvent during dissolution. We evaluated the following disintegrants in this study: sodium starch glycolate (Glycolys), crospovidone (Kollidon CL), carboxymethylcellulose calcium (CMC-Ca), low-substituted hydroxypropylcellulose (L-HPC), and croscarmellose sodium (Ac-Di-Sol). When disintegrant was added to a 50% ethenzamide tablet formulation, an increase in the dissolution rate dependent on disintegrant concentration was observed, according to the type of disintegrant. In addition, the available surface area also differed between disintegrants. For Glycolys, CMC-Ca, and Ac-Di-Sol, a rapid increase in available surface area and a large increase in maximum available surface area (Smax) were observed due to high swellability and wicking, even when the disintegrant concentration was only 1.0%. In contrast, for Kollidon CL and LH-21, a gradual increase in available surface area was observed, depending on the disintegrant concentration. To evaluate the disintegrant ability, Δtmax and ΔSmax were calculated by subtracting peak time (tmax) at 5.0% from that at 1.0% and subtracting Smax at 1.0% from that at 5.0%, respectively, and it was found that the water absorption ratio had strong negative correlations with Δtmax and ΔSmax. Therefore, this study demonstrates that analysis of only available surface area and parameters thereby obtained can directly provide useful information, especially about the disintegration ability of disintegrants. Copyright © 2013 Elsevier B.V. All rights reserved.

Disintegration of sublingual tablets: proposal for a validated test method and acceptance criterion.

PubMed

Weda, M; van Riet-Nales, D A; van Aalst, P; de Kaste, D; Lekkerkerker, J F F

2006-12-01

In the Netherlands the market share of isosorbide dinitrate 5 mg sublingual tablets is dominated by 2 products (A and B). In the last few years complaints have been received from health care professionals on product B. During patient use the disintegration of the tablet was reported to be slow and/or incomplete, and ineffectiveness was experienced. In the European Pharmacopoeia (Ph. Eur.) no requirement is present for the disintegration time of sublingual tablets. The purpose of this study was to compare the in vitro disintegration time of products A and B, and to establish a suitable test method and acceptance criterion. A and B were tested with the Ph. Eur. method described in the monograph on disintegration of tablets and capsules as well as with 3 modified tests using the same Ph. Eur. apparatus, but without movement of the basket-rack assembly. In modified test 1 and modified test 2 water was used as medium (900 ml and 50 ml respectively), whereas in modified test 3 artificial saliva was used (50 ml). In addition, disintegration was tested in Nessler tubes with 0.5 and 2 ml of water. Finally, the Ph. Eur. method was also applied to other sublingual tablets with other drug substances on the Dutch market. With modified test 3 no disintegration could be achieved within 20 min. With the Ph. Eur. method and modified tests 1 and 2 product A and B differed significantly (p < 0. 001), with product B having longer disintegration times. These 3 methods were capable of discriminating between products and between batches. The time measured with the Ph. Eur. method was significantly lower compared to modified tests 1 and 2 (p < 0.001) and correlated well with the Nessler tube results. It is concluded that the in vivo complaints on product B could be related to the in vitro data. Furthermore, it is proposed that for immediate release of sublingual tablets the disintegration time should be tested. The Ph. Eur. method is considered suitable for this test. In view of the products currently on the market and taking into consideration requirements in the United States Pharmacopeia and Japanese Pharmacopoeia, an acceptance criterion of not more than 2 min is proposed.

Quantitative evaluation of the disintegration of orally rapid disintegrating tablets by X-ray computed tomography.

PubMed

Otsuka, Makoto; Yamanaka, Azusa; Uchino, Tomohiro; Otsuka, Kuniko; Sadamoto, Kiyomi; Ohshima, Hiroyuki

2012-01-01

To measure the rapid disintegration of Oral Disintegrating Tablets (ODT), a new test (XCT) was developed using X-ray computing tomography (X-ray CT). Placebo ODT, rapid disintegration candy (RDC) and Gaster®-D-Tablets (GAS) were used as model samples. All these ODTs were used to measure oral disintegration time (DT) in distilled water at 37±2°C by XCT. DTs were affected by the width of mesh screens, and degree to which the tablet holder vibrated from air bubbles. An in-vivo tablet disintegration test was performed for RDC using 11 volunteers. DT by the in-vivo method was significantly longer than that using the conventional tester. The experimental conditions for XCT such as the width of the mesh screen and degree of vibration were adjusted to be consistent with human DT values. Since DTs by the XCT method were almost the same as the human data, this method was able to quantitatively evaluate the rapid disintegration of ODT under the same conditions as inside the oral cavity. The DTs of four commercially available ODTs were comparatively evaluated by the XCT method, conventional tablet disintegration test and in-vivo method.

Enhancement of ultrasonic disintegration of sewage sludge by aeration.

PubMed

Zhao, He; Zhang, Panyue; Zhang, Guangming; Cheng, Rong

2016-04-01

Sonication is an effective way for sludge disintegration, which can significantly improve the efficiency of anaerobic digestion to reduce and recycle use of sludge. But high energy consumption limits the wide application of sonication. In order to improve ultrasonic sludge disintegration efficiency and reduce energy consumption, aeration was introduced. Results showed that sludge disintegration efficiency was improved significantly by combining aeration with ultrasound. The aeration flow rate, gas bubble size, ultrasonic density and aeration timing had impacts on sludge disintegration efficiency. Aeration that used in later stage of ultrasonic irradiation with low aeration flow rate, small gas bubbles significantly improved ultrasonic disintegration sludge efficiency. At the optimal conditions of 0.4 W/mL ultrasonic irradiation density, 30 mL/min of aeration flow rate, 5 min of aeration in later stage and small gas bubbles, ultrasonic sludge disintegration efficiency was increased by 45% and one third of ultrasonic energy was saved. This approach will greatly benefit the application of ultrasonic sludge disintegration and strongly promote the treatment and recycle of wastewater sludge. Copyright © 2015. Published by Elsevier B.V.

Maltodextrin: a novel excipient used in sugar-based orally disintegrating tablets and phase transition process.

PubMed

Elnaggar, Yosra Shaaban R; El-Massik, Magda A; Abdallah, Ossama Y; Ebian, Abd Elazim R

2010-06-01

The recent challenge in orally disintegrating tablets (ODT) manufacturing encompasses the compromise between instantaneous disintegration, sufficient hardness, and standard processing equipment. The current investigation constitutes one attempt to fulfill this challenge. Maltodextrin, in the present work, was utilized as a novel excipient to prepare ODT of meclizine. Tablets were prepared by both direct compression and wet granulation techniques. The effect of maltodextrin concentrations on ODT characteristics--manifested as hardness and disintegration time--was studied. The effect of conditioning (40 degrees C and 75% relative humidity) as a post-compression treatment on ODT characteristics was also assessed. Furthermore, maltodextrin-pronounced hardening effect was investigated using differential scanning calorimetry (DSC) and X-ray analysis. Results revealed that in both techniques, rapid disintegration (30-40 s) would be achieved on the cost of tablet hardness (about 1 kg). Post-compression conditioning of tablets resulted in an increase in hardness (3 kg), while keeping rapid disintegration (30-40 s) according to guidance of the FDA for ODT. However, direct compression-conditioning technique exhibited drawbacks of long conditioning time and appearance of the so-called patch effect. These problems were, yet, absent in wet granulation-conditioning technique. DSC and X-ray analysis suggested involvement of glass-elastic deformation in maltodextrin hardening effect. High-performance liquid chromatography analysis of meclizine ODT suggested no degradation of the drug by the applied conditions of temperature and humidity. Overall results proposed that maltodextrin is a promising saccharide for production of ODT with accepted hardness-disintegration time compromise, utilizing standard processing equipment and phenomena of phase transition.

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).

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process.

PubMed

Pandey, Preetanshu; Levins, Christopher; Pafiakis, Steve; Zacour, Brian; Bindra, Dilbir S; Trinh, Jade; Buckley, David; Gour, Shruti; Sharif, Shasad; Stamato, Howard

2018-07-01

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2 (4-1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p < .0001), atomization air pressure (p = .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.

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.

Strength Enhancement and Application Development of Carbon Foam for Thermal Management Systems

DTIC Science & Technology

2004-01-01

STRENGTH ENHANCEMENT AND APPLICATION DEVELOPMENT OF CARBON FOAM FOR THERMAL MANAGEMENT SYSTEMS Mr. Christopher Duston Ceramic Composites, Inc ...inherent weakness and friability of the carbon foams. Ceramic Composites Inc . has demonstrated the ability to increase the compressive strength by 2½ times...250%.iv In Thermal Protection Systems (TPS) there are two approaches under consideration for utilizing carbon foams. Allcomp Inc.v, Materials and

Production and characterization of pellets using Avicel CL611 as spheronization aid.

PubMed

Puah, Sin Yee; Yap, Hsiu Ni; Chaw, Cheng Shu

2014-03-01

The study looked into the feasibility of producing pellet using Avicel CL611 as spheronization aid by the extrusion/spheronization technique. Pellets were formulated to contain either 20% or 40% Avicel CL611 and lactose monohydrate as the other sole ingredient. Water is used as liquid binder. Quality of pellets and extrudates were analyzed for size distribution, shape, surface tensile strength and disintegration profile. More water was needed when higher Avicel CL611 fraction was used during the production of pellets. The pellets of larger size were obtained by increasing the water content. Pellets with aspect ratios of ∼1.1 were produced with high spheronization speed at short residence time. Higher tensile strength was achieved when increasing the water content and the fraction of Avicel CL611 during pellet production. These pellets also took longer time to disintegrate, nonetheless all the pellets disintegrated within 15 min. A positive linear relationship was obtained between the tensile strength and time for pellets to disintegrate. Strong but round pellets that disintegrate rapidly could be produced with Avicel CL611 as spheronization aid using moderately soluble compounds such as lactose.

[Preparation and evaluation of taste masked orally disintegrating tablets with granules made by the wet granulation method].

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu; Onishi, Hiraku

2010-12-01

Using furosemide (FU) as a model drug, we examined the wet granulation method as a way to improve the taste masking and physical characteristics of orally disintegrating tablets (ODTs). In the wet granulation method, yogurt powder (YO) was used as a corrective and maltitol (MA) was used as a binding agent. The taste masked FU tablets were prepared using the direct compression method. Microcrystalline cellulose (Avicel® PH-302) and mannitol were added as excipients at a mixing ratio of 1/1 by weight. Based on the results of sensory test on taste, the prepared granules markedly improved the taste of FU, and a sufficient masking effect was obtained at the YO/FU ratio of 1 or more. Furthermore, it was found that the masking effect achieved by YO granules made with the wet granulation method was similar to or better than that produced by the granules made with dry granulation method. All types of tablets displayed sufficient hardness (over 3.5×10(-2) kN), and rapidly disintegrating tablets were obtained with YO granules produced at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s. Disintegration time lengthened as the mixing ratio of YO to FU increased. In the mixing ratio of FU/YO=1/1, the hardness of tablets with granules made by the wet granulation method exceeded that of tablets with granules made by the dry granulation method, with minimal differences in disintegration time. The hardness and disintegration time of the tablets with granules made by the wet granulation method could be controlled by varying the compression force. In conclusion, YO was found to be a useful additive for masking unpleasant tastes. FU ODTs with improved taste, rapid disintegration and greater hardness could be prepared with YO-containing granules made by the wet granulation method using MA as a binding agent.

Application of freeze-drying technology in manufacturing orally disintegrating films.

PubMed

Liew, Kai Bin; Odeniyi, Michael Ayodele; Peh, Kok-Khiang

2016-01-01

Freeze drying technology has not been maximized and reported in manufacturing orally disintegrating films. The aim of this study was to explore the freeze drying technology in the formulation of sildenafil orally disintegrating films and compare the physical properties with heat-dried orally disintegrating film. Central composite design was used to investigate the effects of three factors, namely concentration of carbopol, wheat starch and polyethylene glycol 400 on the tensile strength and disintegration time of the film. Heat-dried films had higher tensile strength than films prepared using freeze-dried method. For folding endurance, freeze-dried films showed improved endurance than heat-dried films. Moreover, films prepared using freeze-dried methods were thicker and had faster disintegration time. Formulations with higher amount of carbopol and starch showed higher tensile strength and thickness whereas formulations with higher PEG 400 content showed better flexibility. Scanning electron microscopy showed that the freeze-dried films had more porous structure compared to the heat-dried film as a result of the release of water molecule from the frozen structure when it was subjected to freeze drying process. The sildenafil film was palatable. The dissolution profiles of freeze-dried and heat-dried films were similar to Viagra® with f2 of 51.04 and 65.98, respectively.

Methylphenidate disintegration from oral formulations for intravenous use by experienced substance users.

PubMed

Bjarnadottir, G D; Johannsson, M; Magnusson, A; Rafnar, B O; Sigurdsson, E; Steingrimsson, S; Asgrimsson, V; Snorradottir, I; Bragadottir, H; Haraldsson, H M

2017-09-01

Methylphenidate (MPH) is a prescription stimulant used to treat attention-deficit hyperactivity disorder. MPH is currently the preferred substance among most intravenous (i.v.) substance users in Iceland. Four types of MPH preparations were available in Iceland at the time of study: Immediate-release (IR), sustained-release (SR), osmotic controlled-release oral delivery (OROS) tablet and osmotic-controlled release (OCR). MPH OROS has previously been rated the least desirable by i.v. users and we hypothesized that this was associated with difficulty of disintegrating MPH from OROS formulation. The aim of the study was to measure the amount of MPH and the viscosity of the disintegrated solutions that were made from the four MPH formulations by four i.v.-users and non-users. A convenience sample of four i.v. substance users and 12 non-users. Non-users imitated the methods applied by experienced i.v. substance users for disintegrated MPH formulations. Both groups managed to disintegrate over 50% of MPH from IR and SR formulations but only 20% from OROS (p<0.0001). The viscosity of the disintegrated MPH was significantly higher for MPH OROS and MPH OCR and the preparation was significantly more time-consuming than for the other MPH samples. No differences were observed between users and non-users. To our knowledge, this is the first investigation of viscosity and the amount of disintegrated MPH from prescription drugs for i.v. use. The results indicate that the ease of disintegration, amount of MPH and viscosity may explain the difference in popularity for i.v. use between different MPH formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry.

PubMed

Corá, Luciana A; Romeiro, Fernando G; Américo, Madileine F; Oliveira, Ricardo Brandt; Baffa, Oswaldo; Stelzer, Murilo; Miranda, José Ricardo de Arruda

2006-01-01

The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations.

Effect of deflocculation on photo induced thin layer titanium dioxide disintegration of dairy waste activated sludge for cost and energy efficient methane production.

PubMed

Sharmila, V Godvin; Dhanalakshmi, P; Rajesh Banu, J; Kavitha, S; Gunasekaran, M

2017-11-01

In the present study, the deflocculated sludge was disintegrated through thin layer immobilized titanium dioxide (TiO 2 ) as photocatalyst under solar irradiation. The deflocculation of sludge was carried out by 0.05g/g SS of sodium citrate aiming to facilitate more surface area for subsequent TiO 2 mediated disintegration. The proposed mode of disintegration was investigated by varying TiO 2 dosage, pH and time. The maximum COD solubilization of 18.4% was obtained in the optimum 0.4g/L of TiO 2 dosage with 5.5 pH and exposure time of 40min. Anaerobic assay of disintegrated samples confirms the role of deflocculation as methane yield was found to be higher in deflocculated (235.6mL/gVS) than the flocculated sludge (146.8mL/gVS). Moreover, the proposed method (Net cost for control - Net cost for deflocculation) saves sludge management cost of about $132 with 53.8% of suspended solids (SS) reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disintegration impact on sludge digestion process.

PubMed

Dauknys, Regimantas; Rimeika, Mindaugas; Jankeliūnaitė, Eglė; Mažeikienė, Aušra

2016-11-01

The anaerobic sludge digestion is a widely used method for sludge stabilization in wastewater treatment plant. This process can be improved by applying the sludge disintegration methods. As the sludge disintegration is not investigated enough, an analysis of how the application of thermal hydrolysis affects the sludge digestion process based on full-scale data was conducted. The results showed that the maximum volatile suspended solids (VSS) destruction reached the value of 65% independently on the application of thermal hydrolysis. The average VSS destruction increased by 14% when thermal hydrolysis was applied. In order to have the maximum VSS reduction and biogas production, it is recommended to keep the maximum defined VSS loading of 5.7 kg VSS/m(3)/d when the thermal hydrolysis is applied and to keep the VSS loading between 2.1-2.4 kg VSS/m(3)/d when the disintegration of sludge is not applied. The application of thermal hydrolysis leads to an approximately 2.5 times higher VSS loading maintenance comparing VSS loading without the disintegration; therefore, digesters with 1.8 times smaller volume is required.

ON IMPROVING THE DISINTEGRATION OF AYURVEDIC PILLS CONTAINING GUGGULU

PubMed Central

Chaube, Anjana; Dixit, S.K.; Sharma, P.V.

1995-01-01

An attempt is made in this communication to report a better way of preparing guggulu – containing pills. This technique improves the disintegration time of the preparation, thus enhancing its therapeutic value. PMID:22556694

Time-dependent cell disintegration kinetics in lung tumors after irradiation

NASA Astrophysics Data System (ADS)

Chvetsov, Alexei V.; Palta, Jatinder J.; Nagata, Yasushi

2008-05-01

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T1/2. The half-life T1/2 is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T1/2 of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations.

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

A new apparatus for real-time assessment of the particle size distribution of disintegrating tablets.

PubMed

Quodbach, Julian; Kleinebudde, Peter

2014-11-01

The aim of this study is the introduction of a novel apparatus that is capable of continuously measuring the particle size reduction of disintegrating tablets and analysis of the obtained results. The apparatus is constructed such that no particles pass directly through the pumping system. Thereby, the overall energy input into the particle suspension is reduced, and continuous measurement is possible without rapid destruction of the generated particles. The detected particle sizes at the beginning and at the end of the measurement differ greatly, depending on the applied disintegrant. The median particle sizes at the end of the measurement vary between 621.5 and 178.0 μm for different disintegrants. It is demonstrated that the particle size reduction follows an exponential function and that the fit parameters can be used to describe the disintegration behavior. A strong correlation between the median particle size of crospovidone disintegrants and generated particle size of the tablets is observed. This could be due to a more homogeneous distribution of the disintegrant particles in the tablets. Similar trends are observed for sodium starch glycolate and croscarmellose sodium. The new apparatus provides an innovative method to describe disintegrant effectiveness and efficiency. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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.

Modulation of the wettability of excipients by surfactant and its impacts on the disintegration and release of tablets.

PubMed

Yang, Baixue; Xu, Lu; Wang, Qiuxiao; Li, Sanming

2016-12-01

To investigate the modulation of the wettability of excipients by different types of surfactants and its impacts on the disintegration of tablets and drug release. The critical micelle concentration (CMC) of surfactants, including sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), dodecyl trimethyl ammonium bromide (DTAB), cetyltrimethyl ammonium bromide (CTAB) and polysorbate (Tween-20 and Tween-80), was obtained using the platinum ring method. Contact angles of surfactant solutions on the excipient compacts and double-distilled water on the mixture of surfactant and the other excipient (magnesium stearate (MgSt) or sodium alginate (SA)) were measured by the sessile drop technique. Besides, surface free energy of excipients was calculated by the Owens method. Finally, the disintegration of tablets and in vitro dissolution testing were performed according to the method described in USP. The wettability of excipients could be enhanced to different extent with low concentration of surfactant solutions and maintained stable basically after CMC. For MgSt (hydrophobic excipient), the shorter the hydrophobic chain (C 12 , including SDS and DTAB), the better the wettability with the addition of surfactant in the formulation, leading to the shorter disintegration time of tablets and higher drug release rate. In contrast, the wettability of SA (hydrophilic excipient) was reduced by adding surfactant, resulting in the longer disintegration time of tablets and lower release rate. The modulation of the wetting of pharmaceutical excipients by surfactant had changed the disintegration time of tablets and drug release rate to a greater extent.

Bio-predictive tablet disintegration: effect of water diffusivity, fluid flow, food composition and test conditions.

PubMed

Radwan, Asma; Wagner, Manfred; Amidon, Gordon L; Langguth, Peter

2014-06-16

Food intake may delay tablet disintegration. Current in vitro methods have little predictive potential to account for such effects. The effect of a variety of factors on the disintegration of immediate release tablets in the gastrointestinal tract has been identified. They include viscosity of the media, precipitation of food constituents on the surface of the tablet and reduction of water diffusivity in the media as well as changes in the hydrodynamics in the surrounding media of the solid dosage form. In order to improve the predictability of food affecting the disintegration of a dosage form, tablet disintegration in various types of a liquefied meal has been studied under static vs. dynamic (agitative) conditions. Viscosity, water diffusivity, osmolality and Reynolds numbers for the different media were characterized. A quantitative model is introduced which predicts the influence of the Reynolds number in the tablet disintegration apparatus on the disintegration time. Viscosity, water diffusivity and media flow velocity are shown to be important factors affecting dosage form disintegration. The results suggest the necessity of considering these parameters when designing a predictive model for simulating the in vivo conditions. Based on these experiments and knowledge on in vivo hydrodynamics in the GI tract, it is concluded that the disintegration tester under current pharmacopoeial conditions is operated in an unphysiological mode and no bioprediction may be derived. Recommendations regarding alternative mode of operation are made. Copyright © 2013 Elsevier B.V. All rights reserved.

Fast disintegrating tablets: Opportunity in drug delivery system

PubMed Central

Parkash, Ved; Maan, Saurabh; Deepika; Yadav, Shiv Kumar; Hemlata; Jogpal, Vikas

2011-01-01

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed. PMID:22247889

Preparation of orally disintegrating tablets with taste-masking function: masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules.

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu

2010-01-01

We investigated several methods of taste masking in the preparation of orally disintegrating tablets (ODTs), using furosemide (FU) as a model drug. Four types of FU preparations were prepared: granules with maltitol (MA), granules with yogurt powder (YO), a physical mixture of FU and MA, and a physical mixture of FU and YO. All taste-masking granules were prepared using the dry granulation method. The taste of each type of preparation was evaluated. All four preparations markedly improved the taste of the FU tablets, but the mixing ratios of the correctives did not affect the masking effect. No difference in masking effect was found between MA and YO in the physical mixtures, but the masking effect in the granules with YO was superior to that of the granules with MA. Taste-masked FU tablets were prepared using the direct compression method; crystalline cellulose (Avicel PH-302) and mannitol were added as excipients at the mixing ratio of 1/1. All four types of tablets displayed sufficient hardness, but MA-containing tablets were harder than YO-containing tablets. The hardness of the tablets prepared from YO granules increased as the YO content increased. The most rapidly disintegrating tablets were those of YO granules prepared at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s, followed by the tablets of MA granules prepared at a mixing ratio of FU/MA=1/1. The disintegration times of the tablets made from physical mixtures, in contrast, were longer than 200 s. Disintegration time lengthened as the mixing ratio of YO or MA increased. The hardness and disintegration time of these tablets could be controlled by varying the compression pressure. We found that YO is more useful than MA in masking unpleasant tastes and confirmed that orally disintegrating tablets with taste-masking function can be prepared using granules of YO prepared using the dry granulation method as a new corrective.

Preparation, characterization and in vitro evaluation of a polyvinyl alcohol/sodium alginate based orodispersible film containing sildenafil citrate.

PubMed

Shi, Li-Li; Xu, Wei-Juan; Cao, Qing-Ri; Yang, Mingshi; Cui, Jing-Hao

2014-05-01

In this work, we developed a sildenafil citrate (SC)-loaded polyvinyl alcohol (PVA)/sodium alginate (ALG-Na) based orodispersible film (ODF) using a solvent casting method. Formulation factors such as the type and amount of plasticizers and disintegrants were optimized on the basis of characteristics of blank ODF, including the disintegration time, elastic modulus (EM) and percentage of elongation (E%). SC-loaded ODF with a loading capacity up to 25 mg in an area of 6 cm2 was prepared and evaluated in terms of mechanical properties, disintegration time and dissolution rate. The surface morphology of ODF was visualized under a scanning electron microscope (SEM). The physicochemical properties of ODF were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The blank ODF composed of PVA, polyethylene glycol 400 (PEG 400) and ALG-Na (20:5:2, w/w) had a remarkably short disintegration time of about 20 s. However, the loading of drug extended the disintegration time (100 s) of ODF, while it still maintained satisfactory mechanical properties. SC was homogenously dispersed throughout the films and the crystalline form of drug changed, with strong hydrogen bonding between the drug and carriers. The PVA/ALG-Na based ODF containing SC prepared by the simple solvent casting method might be an alternative to conventional SC tablets for the treatment of male erectile dysfunction.

The impact of temporal variability of excess sludge characteristics on the effects obtained in the process of its ultrasonic disintegration.

PubMed

Tytła, Malwina; Zielewicz, Ewa

2017-09-13

This paper aimed to indicate the characteristics of excess sludge, which have the greatest impact on the effects obtained during its ultrasonic disintegration (UD). The direct and technological effects observed after sludge disintegration and anaerobic digestion (AD) depend on the factors affecting the quality of its matrix and simply on the parameters of a disintegrator. Sludge samples originate from a Central Waste Water Treatment Plant in Gliwice, and were collected after mechanical thickening by a monthly period. This approach allowed to observe the temporal changes of sludge characteristics, in a continuous manner. To evaluate the achieved disintegration effects, the following indicators were used: degree of disintegration (DD COD ) and the author's indicators describing the direct and technological effects of UD (ID i , IT i , IT d ), based on the changes in the sludge characteristics. Disintegration was carried out by means of an ultrasonic device equipped with a thin sonotrode. AD was conducted under mesophilic conditions for 20 days. Statistical analysis confirmed that the most important parameters of sludge, which determine obtained effects, were total and volatile solids, capillary suction time, concentration of chemical oxygen demand and pH value. The investigations have also showed that the increase in sludge temperature during its disintegration has a significant impact on the magnitude of other effects obtained in the process.

Influence of pH on in vitro disintegration of phosphate binders.

PubMed

Stamatakis, M K; Alderman, J M; Meyer-Stout, P J

1998-11-01

Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.

Fast disintegrating films containing anastrozole as a dosage form for dysphagia patients.

PubMed

Satyanarayana, Dixit Anil; Keshavarao, Kulkarni Parthasarathi

2012-12-01

The objective of the present research was to ensure safety during oral administration of medications to dysphagia patients, by preparing fast disintegrating films (FDF) containing anastrozole (ANS) which disintegrate rapidly when placed on the tongue. Films were prepared by solvent-casting method using various polymers such as hydroxyl propyl methyl cellulose (HPMC E5 LV), hydroxy propyl cellulose (HPC), poly vinyl alcohol (PVA) and sodium alginate (Na Alginate). Among the formulations examined, film prepared using HPMC E5 LV (F1) exhibited shorter disintegration time (15 sec) with satisfactory mechanical properties. Fourier transformer infrared (FTIR) & differential scanning calorimetry (DSC) analysis revealed no chemical incompatibility between drug and excipients used in the formulation. Surface morphology revealed even distribution of ANS in the film. Dissolution of drug from F1 formulation was rapid with more than 90% drug release in 240 sec. Pharmacokinetic parameters showed no statistical difference between F1 (test) and drug solution (control) indicating comparable plasma level-time profiles. The film showed an excellent stability for 24 weeks when stored at refrigerated temperature (2-8°C). These findings suggest that the fast disintegrating film as a promising candidate for delivery of ANS in dysphagic patients.

Release kinetics of papaverine hydrochloride from tablets with different excipients.

PubMed

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

PubMed Central

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

Abstract The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release. PMID:25853076

Ultrasonic waste activated sludge disintegration for improving anaerobic stabilization.

PubMed

Tiehm, A; Nickel, K; Zellhorn, M; Neis, U

2001-06-01

The pretreatment of waste activated sludge by ultrasonic disintegration was studied in order to improve the anaerobic sludge stabilization. The ultrasound frequency was varied within a range from 41 to 3217 kHz. The impact of different ultrasound intensities and treatment times was examined. Sludge disintegration was most significant at low frequencies. Low-frequency ultrasound creates large cavitation bubbles which upon collapse initiate powerful jet streams exerting strong shear forces in the liquid. The decreasing sludge disintegration efficiency observed at higher frequencies was attributed to smaller cavitation bubbles which do not allow the initiation of such strong shear forces. Short sonication times resulted in sludge floc deagglomeration without the destruction of bacteria cells. Longer sonication brought about the break-up of cell walls, the sludge solids were distintegrated and dissolved organic compounds were released. The anaerobic digestion of waste activated sludge following ultrasonic pretreatment causing microbial cell lysis was significantly improved. There was an increase in the volatile solids degradation as well as an increase in the biogas production. The increase in digestion efficiency was proportional to the degree of sludge disintegration. To a lesser degree the deagglomeration of sludge flocs also augmented the anaerobic volatile solids degradation.

Formulation of multiparticulate systems as lyophilised orally disintegrating tablets.

PubMed

Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R

2011-11-01

The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Friability Testing as a New Stress-Stability Assay for Biopharmaceuticals.

PubMed

Torisu, Tetsuo; Maruno, Takahiro; Yoneda, Saki; Hamaji, Yoshinori; Honda, Shinya; Ohkubo, Tadayasu; Uchiyama, Susumu

2017-10-01

A cycle of dropping and shaking a vial containing antibody solution was reported to induce aggregation. In this study, antibody solutions in glass prefillable syringes with or without silicone oil lubrication were subjected to the combined stresses of dropping and shaking, using a friability testing apparatus. Larger numbers of subvisible particles were generated, regardless of silicone oil lubrication, upon combination stress exposure than that with shaking stress alone. Nucleation of antibody molecules upon perturbation by an impact of dropping and adsorption of antibody molecules to the syringe surface followed by film formation and antibody film desorption were considered key steps in the particle formation promoted by combination stress. A larger number of silicone oil droplets was released when silicone oil-lubricated glass syringes containing phosphate buffer saline were exposed to combination stress than that observed with shaking stress alone. Polysorbate 20, a non-ionic surfactant, effectively reduced the number of protein particles, but failed to prevent silicone oil release upon combination stress exposure. This study indicates that stress-stability assays using the friability testing apparatus are effective for assessing the stability of biopharmaceuticals under the combined stresses of dropping and shaking, which have not been tested in conventional stress-stability assays. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Interaction of lactoferrin and lysozyme with casein micelles.

PubMed

Anema, Skelte G; de Kruif, C G Kees

2011-11-14

On addition of lactoferrin (LF) to skim milk, the turbidity decreases. The basic protein binds to the caseins in the casein micelles, which is then followed by a (partial) disintegration of the casein micelles. The amount of LF initially binding to casein micelles follows a Langmuir adsorption isotherm. The kinetics of the binding of LF could be described by first-order kinetics and similarly the disintegration kinetics. The disintegration was, however, about 10 times slower than the initial adsorption, which allowed investigating both phenomena. Kinetic data were also obtained from turbidity measurements, and all data could be described with one equation. The disintegration of the casein micelles was further characterized by an activation energy of 52 kJ/mol. The initial increase in hydrodynamic size of the casein micelles could be accounted for by assuming that it would go as the cube root of the mass using the adsorption and disintegration kinetics as determined from gel electrophoresis. The results show that LF binds to casein micelles and that subsequently the casein micelles partly disintegrate. All micelles behave in a similar manner as average particle size decreases. Lysozyme also bound to the casein micelles, and this binding followed a Langmuir adsorption isotherm. However, lysozyme did not cause the disintegration of the casein micelles.

Evaluation of Gum of Moringa oleifera as a Binder and Release Retardant in Tablet Formulation

PubMed Central

Panda, D. S.; Choudhury, N. S. K.; Yedukondalu, M.; Si, S.; Gupta, R.

2008-01-01

The present study was undertaken to find out the potential of gum from Moringa oleifera to act as a binder and release retardant in tablet formulations. The effect of calcium sulphate dihydrate (water insoluble) and lactose (water soluble) diluent on the release of propranolol hydrochloride was studied. The DSC thermograms of drug, gum and mixture of gum/drug indicated no chemical interaction. Tablets (F1, F2, F3, and F4) were prepared containing calcium sulphate dihydrate as diluent, propranolol hydrochloride as model drug using 10%, 8%, 6% and 4% w/v of gum solution as binder. Magnesium stearate was used as lubricant. Physical and technological properties of granules and tablets like flow rate, Carr index, Hausner ratio, angle of repose, hardness, friability and disintegration time were determined and found to be satisfactory. Tablets were prepared by wet granulation method containing calcium sulphate dihydrate as excipient, propranolol hydrochloride as model drug using 10%, 20% and 30% of gum as release retardant, magnesium stearate was used as lubricant. Similarly tablets were prepared replacing lactose with calcium sulphate dihydrate. Despite of the widely varying physico-chemical characteristics of the excipients, the drug release profiles were found to be similar. The drug release increased with increasing proportions of the excipient and decreased proportion of the gum irrespective of the solubility characteristics of the excipient. The values of release exponent ‘n’ are between 0.37 and 0.54. This implies that the release mechanism is Fickian. There is no evidence that the dissolution or erosion of the excipient has got any effect on the release of the drug. The t50% values for tablets containing calcium sulphate dihydrate were on an average 10%-15% longer than the tablets containing lactose as excipient. These relatively small differences in t50% values suggest that the nature of excipient used appeared to play a minor role in regulating the release, while the gum content was a major factor. PMID:21394258

Formulation of an aloe-based product according to Iranian traditional medicine and development of its analysis method.

PubMed

Moein, Elham; Hajimehdipoor, Homa; Toliyat, Tayebeh; Choopani, Rasool; Hamzeloo-Moghadam, Maryam

2017-08-29

Currently, people are more interested to traditional medicine. The traditional formulations should be converted to modern drug delivery systems to be more acceptable for the patients. In the present investigation, a poly herbal medicine "Ayarij-e-Faiqra" (AF) based on Iranian traditional medicine (ITM) has been formulated and its quality control parameters have been developed. The main ingredients of AF including barks of Cinnamomum zeylanicum Blume and Cinnamomum cassia J. Presl, the rhizomes of Nardostachys jatamansi DC., the fruits of Piper cubeba L.f., the flowers of Rosa damascena Herrm., the oleo gum resin of Pistacia terebinthus L. and Aloe spp. dried juice were powdered and used for preparing seven tablet formulations of the herbal mixture. Flowability of the different formulated powders was examined and the best formulations were selected (F6&F7). The tablets were prepared from the selected formulations compared according to the physical characteristics and finally, F7 was selected and coated. Physicochemical characters of core and coated AF tablets were determined and the HPLC method for quantitation of aloin as a marker of tablets was selected and verified according to selectivity, linearity, precision, recovery, LOD and LOQ. The results showed that core and coated AF tablets were in agreement with USP requirements for herbal drugs. They had acceptable appearance, disintegration time, friability, hardness, dissolution behavior, weight variation and content uniformity. The amount of aloin in tablets was found 123.1 mg/tab. The HPLC method for aloin determination in AF tablets was verified according to selectivity, linearity (5-500 μg/ml, r 2 :0.9999), precision (RSD: 1.62%), recovery (108.0%), LOD & LOQ (0.0053 & 0.0161 μg/ml). The formulated tablets could be a good substitute for powder and capsules of AF in ITM clinics with a feasible and precise method for its quality control. Ayarij-e-Faiqra formulation.

Formulation design of ranitidine hydrochloride to reduce its moisture absorption characteristics.

PubMed

Khan, Shagufta; Giradkar, Praful; Yeole, Pramod

2009-01-01

This investigation examined the effect of a ranitidine hydrocholoride (RHCl)-ion exchange resin complexation on the drug's moisture uptake behavior. Drug resin complexes (DRCs) were prepared using the batch method with (i) two weak cation exchange resins, Polacrilex with exchangeable H+ and Polacrillin potassium; and (ii) a strong cation exchange resin;Sodium polystyrene sulfonate. RHCl, simple resins, and DRCs were subjected to storage stability under 40 +/- 2 degrees C and 75 +/- 5% relative humidity (RH) for 16 h, and the resulting percent increase in weight was calculated. DRCs gained less moisture than the simple drug and free resins. Out of the three complexes tested, DRC containing Polacrilex resin showed the most promising effect in protecting RHCl against moisture uptake with an increase in weight of 10.22 +/- 17% (free RHCl gained 28.11%) and was thereby selected for tablet formulation. Tablets were prepared using simple RHCl with Starch 1500 (F1); low moisture-grade Starch 1500 LM (F2); RHCl as DRC with Starch 1500 (F3); and, Starch 1500 LM (F4). Tablets were tested for equilibrium moisture content (EMC) under different humidity conditions and hygroscopicity in the presence and absence of light. In addition, stability studies were run over the duration of 6 months in conditions under 40 +/- 2 degrees C and 75 +/- 5% RH. The EMC of tablets at 80% RH decreased in the following order: F1 > F2 > marketed coated tablet > F3 > F4. The results of hygroscopicity testing revealed that both rate and extent of moisture gain in the presence or absence of light by F3 and F4 were significantly less than F1, F2, and marketed coated tablet (P < 0.05). Stability studies showed insignificant changes in weight, breaking force, friability, and disintegration time for tablets containing resin, while significant changes in these properties were found in tablets without resin. Thus, Polacrilex resin with exchangeable H+ was found to be the best for protecting RHCl against moisture uptake.

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements.

PubMed

Markl, Daniel; Sauerwein, Johanna; Goodwin, Daniel J; van den Ban, Sander; Zeitler, J Axel

2017-05-01

The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. The disintegration time (R 2  = 0.86) and API dissolved after 15 min (R 2  = 0.96) linearly correlates with the effective refractive index, n eff , measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff , we observed a better correlation with dissolution after 20 min (R 2  = 0.96) and a weaker correlation with disintegration (R 2  = 0.83) compared to n eff . The measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to measure content uniformity and the fact that the method requires no chemometric models this technology shows clear promise to be established as a process analyser to non-destructively predict critical quality attributes of tablets.

Composition, disintegrative properties, and labeling compliance of commercially available taurine and carnitine dietary products.

PubMed

Bragg, Rebecca R; Freeman, Lisa M; Fascetti, Andrea J; Yu, Zengshou

2009-01-15

To test the quality, disintegration properties, and compliance with labeling regulations for representative commercially available taurine and carnitine dietary products. Evaluation study. 11 commercially available taurine and 10 commercially available carnitine products. For each product, the amount of taurine or carnitine was determined and compared with the label claim. All products were evaluated for concentrations of mercury, arsenic, and selenium. Disintegration properties of 5 taurine and 8 carnitine products were determined in vitro. Labels were evaluated for compliance with FDA guidelines. 10 of 11 taurine and 10 of 10 carnitine products were within 10% of the stated label claim. Three of 11 taurine and 6 of 10 carnitine products were within 5% of the stated label claim. The median percentage difference between laboratory analysis and label claim was -5.7% (range, -26.3% to 2.5%) for taurine and 3.6% (range, -2.6% to 8.8%) for carnitine. No substantial amount of contamination with mercury, arsenic, or selenium was found in any of the products. During disintegration testing, 1 of 5 taurine products and 5 of 8 carnitine products did not disintegrate within 45 minutes during at least 1 test. Disintegration time for those that did disintegrate ranged from 1.7 to 37.0 minutes. All product labels conformed with FDA regulations. Taurine and carnitine products evaluated in this study closely adhered to manufacturer claims and labeling guidelines. However, disintegration testing suggested high variability in some products, possibly limiting uptake and use by animals that receive them.

Test of cold asphalt storability based on alternative approaches

NASA Astrophysics Data System (ADS)

Abaffyová, Zora; Komačka, Jozef

2017-09-01

Cold asphalt products for potholes repairs should be workable (soft enough) for long time to ensure their applicability. Storability is assessed indirectly using various tests of workability. Therefore, simple test methods (self-compaction and disintegration test) was developed and verified to investigate changes of storability of this group of cold asphalts. Selfcompaction of the tested mixture in the upturned Abram’s cone for the cement concrete slump test and in the mould for the California Bearing Ratio test was assessed in first stage. After that the video record of disintegration test was taken. During this test, the mould was lifted up and the mixture fell off the mould (Abram’s cone) or disintegrate (CBR mould). The drop of surface after 10 min self-compaction and netto time related to falling out or disintegration of the mixture were used to evaluate the mixture from storability point of view. It was found out the self-compaction test has not a potential to reveal and prove changes of mixture properties. Based on the disintegration test results it can be stated this test at 5 °C using the upturned Abram’s cone could be a suitable approach to determine qualitative changes of a cold mixture from storability point of view.

High-Throughput Synthetic Chemistry Enabled by Organic Solvent Disintegrating Tablet.

PubMed

Li, Tingting; Xu, Lei; Xing, Yanjun; Xu, Bo

2017-01-17

Synthetic chemistry remains a time- and labor-intensive process of inherent hazardous nature. Our organic solvent disintegrating tablet (O-Tab) technology has shown potential to make industrial/synthetic chemistry more efficient. As is the case with pharmaceutical tablets, our reagent-containing O-Tabs are mechanically strong, but disintegrate rapidly when in contact with reaction media (organic solvents). For O-Tabs containing sensitive chemicals, they can be further coated to insulate them from air and moisture. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A study of the properties of compacts from silicified microcrystalline celluloses.

PubMed

Muzíková, Jitka; Nováková, Petra

2007-07-01

The paper deals with a study of tensile strength and disintegration time of compacts made from silicified microcrystalline celluloses, Prosolv SMCC 90, and Prosolv HD 90, in dependence on compression force, addition of two types of lubricants, and two active ingredients. The lubricants were magnesium stearate and sodium stearyl fumarate in a concentration of 0.5%, the active ingredients being ascorbic acid and acetylsalicylic acid in a concentration of 50%. Prosolv SMCC 90 proved to be better compatible than Prosolv HD 90; the compacts were of higher strength, which was markedly increased with increasing compression force. Prosolv HD 90 was more sensitive to additions of lubricants, and a greater decrease in strength was recorded due to the influence of sodium stearyl fumarate. The effect of lubricants on the strength of compacts in the presence of active ingredients was not identical. The disintegration time of compacts from Prosolv HD 90 without as well as with lubricants was shorter than from Prosolv SMCC 90 and was increasing with increasing compression force. Disintegration time was increased with added lubricants, and it was markedly shortened by addition of active ingredients. Compacts containing ascorbic acid possessed a shorter disintegration time than those containing acetylsalicylic acid, and it was not markedly influenced by the presence of lubricants.

"Real-time" disintegration analysis and D-optimal experimental design for the optimization of diclofenac sodium fast-dissolving films.

PubMed

El-Malah, Yasser; Nazzal, Sami

2013-01-01

The objective of this work was to study the dissolution and mechanical properties of fast-dissolving films prepared from a tertiary mixture of pullulan, polyvinylpyrrolidone and hypromellose. Disintegration studies were performed in real-time by probe spectroscopy to detect the onset of film disintegration. Tensile strength and elastic modulus of the films were measured by texture analysis. Disintegration time of the films ranged from 21 to 105 seconds whereas their mechanical properties ranged from approximately 2 to 49 MPa for tensile strength and 1 to 21 MPa% for young's modulus. After generating polynomial models correlating the variables using a D-Optimal mixture design, an optimal formulation with desired responses was proposed by the statistical package. For validation, a new film formulation loaded with diclofenac sodium based on the optimized composition was prepared and tested for dissolution and tensile strength. Dissolution of the optimized film was found to commence almost immediately with 50% of the drug released within one minute. Tensile strength and young's modulus of the film were 11.21 MPa and 6, 78 MPa%, respectively. Real-time spectroscopy in conjunction with statistical design were shown to be very efficient for the optimization and development of non-conventional intraoral delivery system such as fast dissolving films.

Disintegration Test of Health Food Products Containing Ginkgo Biloba L. or Vitex Agnus-Castus L. in the Japanese Market.

PubMed

Sato-Masumoto, Naoko; Masada, Sayaka; Takahashi, Satoshi; Terasaki, Sachiko; Yokota, Yoichi; Hakamatsuka, Takashi; Goda, Yukihiro

2015-04-23

For many years now, a number of Western herbs have been widely used in health food products in Japan and as pharmaceuticals in Europe. There are few or no mandated criteria concerning the quality of these herbal health food products, thus clarification is warranted. Here, we performed disintegration tests of 26 pharmaceutical and health food products containing the Western herbs ginkgo leaf and chaste tree fruit, in accord with the Japanese Pharmacopoeia. All eight pharmaceutical herbal products found in the European market completely disintegrated within the defined test time, and 11 of the 18 tested herbal products distributed as health foods in Japan disintegrated. Among the incompatible products identified in the Pharmacopoeia test, some products remained intact after incubation in water for 60 min. To ensure the efficacy of Western herbal products sold as health food in Japan, quality control, including disintegration, is therefore recommended, even though these products are not regulated under the Pharmaceutical Affairs Law.

Disintegration Test of Health Food Products Containing Ginkgo Biloba L. or Vitex Agnus-Castus L. in the Japanese Market

PubMed Central

Sato-Masumoto, Naoko; Masada, Sayaka; Takahashi, Satoshi; Terasaki, Sachiko; Yokota, Yoichi; Hakamatsuka, Takashi; Goda, Yukihiro

2015-01-01

For many years now, a number of Western herbs have been widely used in health food products in Japan and as pharmaceuticals in Europe. There are few or no mandated criteria concerning the quality of these herbal health food products, thus clarification is warranted. Here, we performed disintegration tests of 26 pharmaceutical and health food products containing the Western herbs ginkgo leaf and chaste tree fruit, in accord with the Japanese Pharmacopoeia. All eight pharmaceutical herbal products found in the European market completely disintegrated within the defined test time, and 11 of the 18 tested herbal products distributed as health foods in Japan disintegrated. Among the incompatible products identified in the Pharmacopoeia test, some products remained intact after incubation in water for 60 min. To ensure the efficacy of Western herbal products sold as health food in Japan, quality control, including disintegration, is therefore recommended, even though these products are not regulated under the Pharmaceutical Affairs Law. PMID:28930200

Modified ADM1 disintegration/hydrolysis structures for modeling batch thermophilic anaerobic digestion of thermally pretreated waste activated sludge.

PubMed

Ramirez, Ivan; Mottet, Alexis; Carrère, Hélène; Déléris, Stéphane; Vedrenne, Fabien; Steyer, Jean-Philippe

2009-08-01

Anaerobic digestion disintegration and hydrolysis have been traditionally modeled according to first-order kinetics assuming that their rates do not depend on disintegration/hydrolytic biomass concentrations. However, the typical sigmoid-shape increase in time of the disintegration/hydrolysis rates cannot be described with first-order models. For complex substrates, first-order kinetics should thus be modified to account for slowly degradable material. In this study, a slightly modified IWA ADM1 model is presented to simulate thermophilic anaerobic digestion of thermally pretreated waste activated sludge. Contois model is first included for disintegration and hydrolysis steps instead of first-order kinetics and Hill function is then used to model ammonia inhibition of aceticlastic methanogens instead of a non-competitive function. One batch experimental data set of anaerobic degradation of a raw waste activated sludge is used to calibrate the proposed model and three additional data sets from similar sludge thermally pretreated at three different temperatures are used to validate the parameters values.

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

PubMed

Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

2007-09-01

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

Important operational parameters of membrane bioreactor-sludge disintegration (MBR-SD) system for zero excess sludge production.

PubMed

Yoon, Seong-Hoon

2003-04-01

In order to prevent excess sludge production during wastewater treatment, a membrane bioreactor-sludge disintegration (MBR-SD) system has been introduced, where the disintegrated sludge is recycled to the bioreactor as a feed solution. In this study, a mathematical model was developed by incorporating a sludge disintegration term into the conventional activated sludge model and the relationships among the operational parameters were investigated. A new definition of F/M ratio for the MBR-SD system was suggested to evaluate the actual organic loading rate. The actual F/M ratio was expected to be much higher than the apparent F/M ratio in MBR-SD. The kinetic parameters concerning the biodegradability of organics hardly affect the system performance. Instead, sludge solubilization ratio (alpha) in the SD process and particulate hydrolysis rate constant (k(h)) in biological reaction determine the sludge disintegration number (SDN), which is related with the overall economics of the MBR-SD system. Under reasonable alpha and k(h) values, SDN would range between 3 and 5 which means the amount of sludge required to be disintegrated would be 3-5 times higher for preventing a particular amount of sludge production. Finally, normalized sludge disintegration rate (q/V) which is needed to maintain a certain level of MLSS in the MBR-SD system was calculated as a function of F/V ratio.

Satellite disintegration dynamics

NASA Technical Reports Server (NTRS)

Dasenbrock, R. R.; Kaufman, B.; Heard, W. B.

1975-01-01

The subject of satellite disintegration is examined in detail. Elements of the orbits of individual fragments, determined by DOD space surveillance systems, are used to accurately predict the time and place of fragmentation. Dual time independent and time dependent analyses are performed for simulated and real breakups. Methods of statistical mechanics are used to study the evolution of the fragment clouds. The fragments are treated as an ensemble of non-interacting particles. A solution of Liouville's equation is obtained which enables the spatial density to be calculated as a function of position, time and initial velocity distribution.

Energy potential of the modified excess sludge

NASA Astrophysics Data System (ADS)

Zawieja, Iwona

2017-11-01

On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4), it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

Dabrowski's Theory of Positive Disintegration and Giftedness: Overexcitability Research Findings

ERIC Educational Resources Information Center

Mendaglio, Sal; Tillier, William

2006-01-01

During the past 20 years, a significant body of literature has emerged focusing on the application of Dabrowski's theory of positive disintegration (TPD) to the study of gifted individuals. Although much of this literature is prescriptive, some research reports spanning this time period are available. A perusal of research on TPD's applicability…

Prevalence of Childhood Disintegrative Disorder.

ERIC Educational Resources Information Center

Fombonne, Eric

2002-01-01

A review of 32 epidemiological surveys of autism and pervasive developmental disorders found four surveys yielded estimates for childhood disintegrative disorder (CDD) ranging from 1.1 to 6.4 per 100,000. It is concluded that CDD is very rare and its prevalence is 60 times less than that of autistic disorder. (Contains references.) (Author/CR)

Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium.

PubMed

Shah, Rakhi B; Collier, Jarrod S; Sayeed, Vilayat A; Bryant, Arthur; Habib, Muhammad J; Khan, Mansoor A

2010-09-01

Levothyroxine is a narrow therapeutic index, and to avoid adverse effect associated with under or excessive dosage, the dose response is carefully titrated. The tablets are marketed with a score providing an option to split. However, there are no systematic studies evaluating the effect of splitting on dose accuracy, and current study was undertaken to evaluate effects of splitting and potential causes for uniformity failures by measuring assay and content uniformity in whole and split tablets. Stability was evaluated by assaying drug for a period of 8 weeks. Effect of formulation factors on splittability was evaluated by a systematic investigation of formulation factors by preparing levothyroxine tablets in house by varying the type of excipients (binder, diluent, disintegrant, glidant) or by varying the processing factors (granulating liquid, mixing type, compression pressure). The tablets were analyzed using novel analytical tool such as near infrared chemical imaging to visualize the distribution of levothyroxine. Assay was not significantly different for whole versus split tablets irrespective of method of splitting (hand or splitter), and splitting also had no measurable impact on the stability. Split tablets either by hand or splitter showed higher rate of content uniformity failures as compared to whole tablets. Tablet splitter produced more fragmentation and, hence, more content uniformity and friability failures. Chemical imaging data revealed that the distribution of levothyroxine was heterogeneous and was dependent on type of binder and the process used in the manufacture of tablets. Splitting such tablets could prove detrimental if sub- or super-potency becomes an issue.

Comparison of sublingual tablets with nitroglycerin complexed with beta-cyclodextrin or titrated with crosspovidone--technological approach.

PubMed

Centkowska, Katarzyna; Sznitowska, Małgorzata

2008-01-01

Fast disintegrating sublingual tablets containing nitroglycerin either complexed with beta-cyclodextrin (NTG-CD) or titrated with crosspovidone (NTG-CP) were prepared using Starch 1500 or StarLac as disintegrants. Regarding disintegration time and stability of the active substance Starch 1500 was more appropriate for NTG-CD while for NTG-CP StarLac was suitable. Stability of NTG was better in NTG-CD tablets than in NTG-CP tablets, however, within 12 months of storage at 25 degrees C the loss of NTG in all formulations was still greater than 10%.

Alkaline treatment of high-solids sludge and its application to anaerobic digestion.

PubMed

Li, Chenchen; Li, Huan; Zhang, Yuyao

2015-01-01

High-solids anaerobic digestion is a promising new process for sludge reduction and bioenergy recovery, requiring smaller digestion tanks and less energy for heating, but a longer digestion time, than traditional low-solids anaerobic digestion. To accelerate this process, alkaline sludge disintegration was tested as a pretreatment method for anaerobic digestion of high-solids sludge. The results showed that alkaline treatment effectively disintegrated both low-solids sludge and high-solids sludge, and treatment duration of 30 min was the most efficient. The relation between sludge disintegration degree and NaOH dose can be described by a transmutative power function model. At NaOH dose lower than 0.2 mol/L, sludge disintegration degree remained virtually unchanged when sludge total solids (TS) content increased from 2.0 to 11.0%, and decreased only slightly when sludge TS increased to 14.2%. Although high-solids sludge required a slightly higher molarity of NaOH to reach the same disintegration level of low-solids sludge, the required mass of NaOH actually decreased due to sludge thickening. From the view of NaOH consumption, sludge TS of 8-12% and a NaOH dose of 0.05 mol/L were optimum conditions for alkaline pretreatment, which resulted in a slight increase in accumulative biogas yield, but a decrease by 24-29% in digestion time during the subsequent anaerobic digestion.

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

In vivo determination of the time and location of mucoadhesive drug delivery systems disintegration in the gastrointestinal tract.

PubMed

Kremser, Christian; Albrecht, Karin; Greindl, Melanie; Wolf, Christian; Debbage, Paul; Bernkop-Schnürch, Andreas

2008-06-01

The objective of this study was to use magnetic resonance imaging (MRI) to detect the time when and the location at which orally delivered mucoadhesive drugs are released. Drug delivery systems comprising tablets or capsules containing a mucoadhesive polymer were designed to deliver the polymer to the intestine in dry powder form. Dry Gd-DTPA [diethylenetriaminepentaacetic acid gadolinium(III) dihydrogen salt hydrate] powder was added to the mucoadhesive polymer, resulting in a susceptibility artifact that allows tracking of the application forms before their disintegration and that gives a strong positive signal on disintegration. Experiments were performed with rats using T(1)-weighted spin-echo imaging on a standard 1.5-T MRI system. The susceptibility artifact produced by the dry Gd-DTPA powder in tablets or capsules was clearly visible within the stomach of the rats and could be followed during movement towards the intestine. Upon disintegration, a strong positive signal was unambiguously observed. The time between ingestion and observation of a positive signal was significantly different for different application forms. Quantification of the remaining mucoadhesive polymer in the intestine 3 h after observed release showed significant differences in mucoadhesive effectiveness. MRI allows detection of the exact time of release of the mucoadhesive polymer in vivo, which is a prerequisite for a reliable quantitative comparison between different application forms.

A Practical Framework Toward Prediction of Breaking Force and Disintegration of Tablet Formulations Using Machine Learning Tools.

PubMed

Akseli, Ilgaz; Xie, Jingjin; Schultz, Leon; Ladyzhynsky, Nadia; Bramante, Tommasina; He, Xiaorong; Deanne, Rich; Horspool, Keith R; Schwabe, Robert

2017-01-01

Enabling the paradigm of quality by design requires the ability to quantitatively correlate material properties and process variables to measureable product performance attributes. Conventional, quality-by-test methods for determining tablet breaking force and disintegration time usually involve destructive tests, which consume significant amount of time and labor and provide limited information. Recent advances in material characterization, statistical analysis, and machine learning have provided multiple tools that have the potential to develop nondestructive, fast, and accurate approaches in drug product development. In this work, a methodology to predict the breaking force and disintegration time of tablet formulations using nondestructive ultrasonics and machine learning tools was developed. The input variables to the model include intrinsic properties of formulation and extrinsic process variables influencing the tablet during manufacturing. The model has been applied to predict breaking force and disintegration time using small quantities of active pharmaceutical ingredient and prototype formulation designs. The novel approach presented is a step forward toward rational design of a robust drug product based on insight into the performance of common materials during formulation and process development. It may also help expedite drug product development timeline and reduce active pharmaceutical ingredient usage while improving efficiency of the overall process. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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.

The Dynamic Mu Transpososome: MuB activation prevents disintegration

PubMed Central

Lemberg, Kathryn M.; Schweidenback, Caterina T. H.; Baker, Tania A.

2007-01-01

Summary DNA transposases use a single active center to sequentially cleave the transposable element DNA and join this DNA to a target site. Recombination requires controlled conformational changes within the transposase to ensure that these chemically distinct steps occur at the right time and place, and that the reaction proceeds in the net forward direction. Mu transposition is catalyzed by a stable complex of MuA transposase bound to paired Mu DNA ends (a transpososome). We find that Mu transpososomes efficiently catalyze disintegration when recombination on one end of the Mu DNA is blocked. The MuB activator protein controls the integration vs. disintegration equilibrium. When MuB is present, disintegration occurs slowly and transpososomes that have disintegrated catalyze subsequent rounds of recombination. In the absence of MuB, disintegration goes to completion. These results together with experiments mapping the MuA-MuB contacts during DNA joining suggest that MuB controls progression of recombination by specifically stabilizing a concerted transition to the ‘joining’ configuration of MuA. Thus, we propose that MuB's interaction with the transpososome actively promotes coupled joining of both ends of the element DNA into the same target site and thus may provide a mechanism to antagonize formation of single-end transposition products. PMID:17988683

Hot-stage microscopy for determination of API particles in a formulated tablet.

PubMed

Simek, Michal; Grünwaldová, Veronika; Kratochvíl, Bohumil

2014-01-01

Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets.

A critical review on tablet disintegration.

PubMed

Quodbach, Julian; Kleinebudde, Peter

2016-09-01

Tablet disintegration is an important factor for drug release and can be modified with excipients called tablet disintegrants. Tablet disintegrants act via different mechanisms and the efficacy of these excipients is influenced by various factors. In this review, the existing literature on tablet disintegration is critically reviewed. Potential disintegration mechanisms, as well as impact factors on the disintegration process will be discussed based on experimental evidence. Search terms for Scopus and Web of Science included "tablet disintegration", "mechanism tablet disintegration", "superdisintegrants", "disintegrants", "swelling force", "disintegration force", "disintegration mechanisms", as well as brand names of commonly applied superdisintegrants. References of identified papers were screened as well. Experimental data supports swelling and shape recovery as main mechanisms of action of disintegrants. Other tablet excipients and different manufacturing techniques greatly influence the disintegration process. The use of different excipients, experimental setups and manufacturing techniques, as well as the demand for original research led to a distinct patchwork of knowledge. Broader, more systematic approaches are necessary not only to structure the past but also future findings.

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.

How EPA's Asbestos Regulations Apply to Transite Siding

EPA Pesticide Factsheets

Letters that provide guidance on asbestos National Emissions Standard of Hazardous Air Pollutants (NESHAP) applicability to transite sliding in demolitions, specifically regarding friability, and removal requirements prior to, and after, demolition.

Disintegration of comet nuclei

NASA Astrophysics Data System (ADS)

Ksanfomality, Leonid V.

2012-02-01

The breaking up of comets into separate pieces, each with its own tail, was seen many times by astronomers of the past. The phenomenon was in sharp contrast to the idea of the eternal and unchangeable celestial firmament and was commonly believed to be an omen of impending disaster, especially for comets with tails stretching across half the sky. It is only now that we have efficient enough space exploration tools to see comet nuclei and even - in the particular case of small comet Hartley-2 in 2010 - to watch their disintegration stage. There are also other suspected candidates for disintegration in the vast family of comet nuclei and other Solar System bodies.

Optimization of magnetic field-assisted ultrasonication for the disintegration of waste activated sludge using Box-Behnken design with response surface methodology.

PubMed

Guan, Su; Deng, Feng; Huang, Si-Qi; Liu, Shu-Yang; Ai, Le-Xian; She, Pu-Ying

2017-09-01

This study investigated for the first time the feasibility of using a magnetic field for sludge disintegration. Approximately 41.01% disintegration degree (DD) was reached after 30min at 180mT magnetic field intensity upon separate magnetic field treatment. Protein and polysaccharide contents significantly increased. This test was optimized using a Box-Behnken design (BBD) with response surface methodology (RSM) to fit the multiple equation of the DD. The maximum DD was 43.75% and the protein and polysaccharide contents increased to 56.71 and 119.44mg/L, respectively, when the magnetic field strength was 119.69mT, reaction time was 30.49min, and pH was 9.82 in the optimization experiment. We then analyzed the effects of ultrasound alone. We are the first to combine magnetic field with ultrasound to disintegrate waste-activated sludge (WAS). The optimum effect was obtained with the application of ultrasound alone at 45kHz frequency, with a DD of about 58.09%. By contrast, 62.62% DD was reached in combined magnetic field and ultrasound treatment. This combined test was also optimized using BBD with RSM to fit the multiple equation of DD. The maximum DD of 64.59% was achieved when the magnetic field intensity was 197.87mT, ultrasonic frequency was 42.28kHz, reaction time was 33.96min, and pH was 8.90. These results were consistent with those of particle size and electron microscopy analyses. This research proved that a magnetic field can effectively disintegrate WAS and can be combined with other physical techniques such as ultrasound for optimal results. Copyright © 2017 Elsevier B.V. All rights reserved.

[Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis].

PubMed

Iwao, Yasunori

2015-01-01

With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg-St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5% showed downward curvature indicating a gradual decrease in surface area over time. Conversely, with TR-FB, even when its concentration was increased, the S(t) profile for APAP had a maximum value. The differences between Mg-St and TR-FB could be explained by the differences in extensibility deriving from their morphology. Next, we evaluated the effect of disintegtant concentration using five disintegrants. When disintegrant was added to ethenzamide tablet formulation, an increase in the dissolution rate and S(t) dependent on disintegrant concentration was observed, according to the type of disintegrant. It was found that the water absorption ability of disintegrants had strong correlations with the parameters of S(t). Taken together, this study demonstrates that analysis of S(t) can directly provide useful information, especially about the functionality of pharmaceutical excipients.

Ultrasound pretreatment of filamentous algal biomass for enhanced biogas production.

PubMed

Lee, Kwanyong; Chantrasakdakul, Phrompol; Kim, Daegi; Kong, Mingeun; Park, Ki Young

2014-06-01

The filamentous alga Hydrodictyon reticulatum harvested from a bench-scale wastewater treatment pond was used to evaluate biogas production after ultrasound pretreatment. The effects of ultrasound pretreatment at a range of 10-5000 J/mL were tested with harvested H. reticulatum. Cell disruption by ultrasound was successful and showed a higher degree of disintegration at a higher applied energy. The range of 10-5000 J/mL ultrasound was able to disintegrated H. reticulatum and the soluble COD was increased from 250 mg/L to 1000 mg/L at 2500 J/mL. The disintegrated algal biomass was digested for biogas production in batch experiments. Both cumulative gas generation and volatile solids reduction data were obtained during the digestion. Cell disintegration due to ultrasound pretreatment increased the specific biogas production and degradation rates. Using the ultrasound approach, the specific methane production at a dose of 40 J/mL increased up to 384 mL/g-VS fed that was 2.3 times higher than the untreated sample. For disintegrated samples, the volatile solids reduction was greater with increased energy input, and the degradation increased slightly to 67% at a dose of 50 J/mL. The results also indicate that disintegration of the algal cells is the essential step for efficient anaerobic digestion of algal biomass. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimization of disintegration behavior of biodegradable poly (hydroxy butanoic acid) copolymer mulch films in soil environment

NASA Astrophysics Data System (ADS)

Mahajan, Viabhav

Biodegradation of polymeric films used for mulch film applications in agriculture not only eliminates problems of sorting out and disposal of plastics films, but also ensures increased yields in crop growth and cost reduction. One such polymer which is completely biodegradable in the soil is poly 3-hydroxy butanoic acid copolymer, which is a promising alternative to non-biodegradable incumbent polyethylene mulch films. The purpose of mulch film made of poly 3-hydroxy butanoic acid copolymers is to sustain itself during the crop growth and disintegrate and eventually biodegrade back to nature after the crop cycle is over. The disintegration phase of the biodegradation process was evaluated for poly 3-hydroxy butanoic acid copolymer incorporated with no additive, antimicrobial additives, varying amount of crystallinities, another biodegradable polymer, and in different soils, with or without varying soil moisture content. The tools used for quantification were weight loss and visual observation. The test method was standardized using repeatability tests. The onset of disintegration was optimized with addition of right anti-microbial additives, higher crystallinity of film, blending with other biodegradable polymers, compared to virgin poly 3-hydroxy butanoic acid copolymer film. The onset of disintegration time was reduced when soil moisture content was reduced. After the onset of disintegration, the polymer film was physically and mechanically deteriorated, withering away in soil, which is possible to tailor with the crop growth cycle.

Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.

PubMed

Tomuta, Ioan; Iovanov, Rares; Bodoki, Ede; Vonica, Loredana

2014-04-01

Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets. The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets. The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method. The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets. The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time). The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.

Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

PubMed

Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

2017-10-01

The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

Formulation and in vitro characterization of novel sildenafil citrate-loaded polyvinyl alcohol-polyethylene glycol graft copolymer-based orally dissolving films.

PubMed

Xu, Li-Li; Shi, Li-Li; Cao, Qing-Ri; Xu, Wei-Juan; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

2014-10-01

This work was aimed to develop novel sildenafil citrate (SC)-loaded polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer (Kollicoat(®) IR)-based orally dissolving films (ODFs) using a solvent casting method. Formulation factors such as plasticizers and disintegrants were optimized on the basis of characteristics of blank ODFs. The SC-loaded ODF with a loading capacity up to 6.25mg in an area of 6 cm(2) was prepared and evaluated in terms of mechanical properties, disintegration time and dissolution rate. The physicochemical properties of drug-loaded ODF were also investigated using the scanning electron microscope (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The blank ODF composed of Kollicoat(®) IR, sodium alginate (ALG-Na) and glycerol (10:2:1.5, w/w) had a remarkably short disintegration time of about 20s. The SC-loaded ODF showed a delayed disintegration time (about 25s), but exhibited improved mechanical properties when compared to the blank ODF. SC was homogeneously dispersed throughout the ODF and the crystalline form of drug had been partly changed, existing strong hydrogen bonding between the drug and carriers. The Kollicoat(®) IR/ALG-Na based ODFs containing SC might be an alternative to conventional tablet for the treatment of male erectile dysfunction. Copyright © 2014 Elsevier B.V. All rights reserved.

Friable but treatable: coronary artery dissections in Ehlers-Danlos syndrome.

PubMed

Zago, Alexandre C; Matte, Bruno S

2013-01-01

Vascular Ehlers-Danlos syndrome is a rare connective tissue disorder associated with arterial dissection or rupture. Percutaneous coronary intervention (PCI) is often critical in patients with this syndrome because their coronary arteries are prone to dissection, enhancing the risk of stent borders dissection when conventional stent deployment pressures are used. Coronary artery bypass graft (CABG) treatment for these patients may also raise concerns because the left internal mammary artery is probably friable. Therefore, coronary artery revascularization in vascular Ehlers-Danlos syndrome either using PCI or CABG is challenging due to the arteries friability. A small number of cases have been published describing the friability of the vessels and associated complications; nevertheless, the optimum treatment remains unclear. We report the case of a 54-year-old woman treated successfully with PCI and CABG in two different acute coronary syndrome episodes, in which specific technical issues related to both procedures were decisive. Copyright © 2011 Wiley Periodicals, Inc.

INFLUENCE OF TYPE AND NEUTRALISATION CAPACITY OF ANTACIDS ON DISSOLUTION RATE OF CIPROFLOXACIN AND MOXIFLOXACIN FROM TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2009-01-01

Dissolution rate of two fluoroquinolone antibiotics (ciprofloxacin and moxifloxacin) was analysed in presence/absence of three antacid formulations. Disintegration time and neutralisation capacity of antacid tablets were also checked. Variation in disintegration time indicated the importance of this parameter, and allowed evaluation of the influence of postponed antacid-fluoroquinolone contact. The results obtained in this study showed decreased dissolution rate of fluoroquinolone antibiotics from tablets in simultaneous presence of antacids, regardless of their type and neutralisation capacity. PMID:19284403

Dynein-ADP as a force-generating intermediate revealed by a rapid reactivation of flagellar axoneme.

PubMed Central

Tani, T; Kamimura, S

1999-01-01

Fragmented flagellar axonemes of sand dollar spermatozoa were reactivated by rapid photolysis of caged ATP. After a time lag of 10 ms, axonemes treated with protease started sliding disintegration. Axonemes without protease digestion started nanometer-scale high-frequency oscillation after a similar time lag. Force development in the sliding disintegration was measured with a flexible glass needle and its time course was corresponded well to that of the dynein-ADP intermediate production estimated using kinetic rates previously reported. However, with a high concentration ( approximately 80 microM) of vanadate, which binds to the dynein-ADP intermediate and forms a stable complex of dynein-ADP-vanadate, the time course of force development in sliding disintegration was not affected at all. In the case of high frequency oscillation, the time lag to start the oscillation, the initial amplitude, and the initial frequency were not affected by vanadate, though the oscillation once started was damped more quickly at higher concentrations of vanadate. These results suggest that during the initial turnover of ATP hydrolysis, force generation of dynein is not blocked by vanadate. A vanadate-insensitive dynein-ADP is postulated as a force-generating intermediate. PMID:10465762

Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using kappa-carrageenan as a pelletizing agent.

PubMed

Kilor, Vaishali A; Sapkal, Nidhi P; Awari, Jasmine G; Shewale, Bharti D

2010-03-01

In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion-spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like beta-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% kappa-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of kappa-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.

Spherical composite particles of rice starch and microcrystalline cellulose: a new coprocessed excipient for direct compression.

PubMed

Limwong, Vasinee; Sutanthavibul, Narueporn; Kulvanich, Poj

2004-03-12

Composite particles of rice starch (RS) and microcrystalline cellulose were fabricated by spray-drying technique to be used as a directly compressible excipient. Two size fractions of microcrystalline cellulose, sieved (MCS) and jet milled (MCJ), having volumetric mean diameter (D50) of 13.61 and 40.51 microm, respectively, were used to form composite particles with RS in various mixing ratios. The composite particles produced were evaluated for their powder and compression properties. Although an increase in the microcrystalline cellulose proportion imparted greater compressibility of the composite particles, the shape of the particles was typically less spherical with rougher surface resulting in a decrease in the degree of flowability. Compressibility of composite particles made from different size fractions of microcrystalline cellulose was not different; however, using MCJ, which had a particle size range close to the size of RS (D50 = 13.57 microm), provided more spherical particles than using MCS. Spherical composite particles between RS and MCJ in the ratio of 7:3 (RS-MCJ-73) were then evaluated for powder properties and compressibility in comparison with some marketed directly compressible diluents. Compressibility of RS-MCJ-73 was greater than commercial spray-dried RS (Eratab), coprocessed lactose and microcrystalline cellulose (Cellactose), and agglomerated lactose (Tablettose), but, as expected, lower than microcrystalline cellulose (Vivapur 101). Flowability index of RS-MCJ-73 appeared to be slightly lower than Eratab but higher than Vivapur 101, Cellactose, and Tablettose. Tablets of RS-MCJ-73 exhibited low friability and good self-disintegrating property. It was concluded that these developed composite particles could be introduced as a new coprocessed direct compression excipient.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics.

PubMed

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

2012-04-01

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure. Copyright © 2011 Elsevier B.V. All rights reserved.

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

PubMed

Vaithianathan, Soundarya; Raman, Siddarth; Jiang, Wenlei; Ting, Tricia Y; Kane, Maureen A; Polli, James E

2015-07-06

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

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.

[Comparison in dissolution behavior of ethical and over-the counter scopolamine butylbromide].

PubMed

Suzuki, Ichie; Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

2011-01-01

Marketing authorization holders do not disclose any information on the pharmaceutical properties of over-the-counter drugs (OTC). When a drug is switched from a prescription drug to OTC, pharmacists can acquire that information from the corresponding ethical drug (ED) through the package insert, interview form, and so on. However, the pharmaceutical equivalence between ED and OTC is unclear. In this study, we examined the drug dissolution behavior of both ED and OTCs containing scopolamine butylbromide. Dissolution tests were performed by the paddle method using Japanese Pharmacopeia (JP) XV test fluids at pH 1.2, 4.0 and 6.8 and water based on the guidelines for bioequivalence studies of generic products. The dissolution profiles of OTCs differed significantly from ED showing a similarity factor (f2) value ranging from 8.9 to 42.9. Time until 85% dissolution ranged from 23 to 95 min and from 17 to 174 min at pH 1.2 and pH 6.8, respectively. Then JP XV disintegration tests were conducted to investigate differences in the disintegration process. The disintegration time of preparations showing delayed dissolution was prolonged compared to that of others, suggesting that the disintegration of the tablet or capsule is one of the important factors affecting the drug dissolution. These differences in the disintegration and drug dissolution might cause differences in the bioavailability of the drug. For patient safety, more detailed product information of OTCs should be supplied by the manufacturer, and not be assumed from that of corresponding ED.

Potential of activated sludge disintegration.

PubMed

Boehler, M; Siegrist, H

2006-01-01

The disposal of sewage sludge and the agricultural use of stabilised sludge are decreasing due to more stringent regulations in Europe. An increasing fraction of sewage sludge must therefore be dewatered, dried, incinerated and the ashes disposed of in landfills. These processes are cost-intensive and also lead to the loss of valuable phosphate resources incorporated in the sludge ash. The implementation of processes that could reduce excess sludge production and recycle phosphate is therefore recommended. Disintegration of biological sludge by mechanical, thermal and physical methods could significantly reduce excess sludge production, improve the settling properties of the sludge and reduce bulking and scumming. The solubilised COD could also improve denitrification if the treated sludge is recycled to the anoxic zone. However, disintegration partly inhibits and kills nitrifiers and could therefore shorten their effective solid retention time, thus reducing the safety of the nitrification. This paper discusses the potential of disintegration on sludge reduction, the operating stability of nitrification, the improvement of denitrification and also presents an energy and cost evaluation.

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.

Evaluation about wettability, water absorption or swelling of excipients through various methods and the correlation between these parameters and tablet disintegration.

PubMed

Yang, Baixue; Wei, Chen; Yang, Yang; Wang, Qifang; Li, Sanming

2018-04-06

To evaluate parameters about wettability, water absorption or swelling of excipients in forms of powders or dosage through various methods systematically and explore its correlation with tablet disintegration. The water penetration and swelling of powders with different proportions of excipients including microcrystalline cellulose (MCC), mannitol, low-substituted hydroxypropyl cellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), carboxymethyl starch sodium (CMS-Na), croscarmellose sodium (CCMC-Na) and magnesium stearate (MgSt) were determined by Washburn capillary rise. Both contact angle of water on the excipient compacts and surface swelling volume were measured by sessile drop technique. Moreover, the test about water absorption and swelling of compacts was fulfilled by a modified method. Eventually, the disintegration of tablets with or without loratadine was performed according to the method described in USP. These parameters were successfully identified by the methods above, which proved that excipient wettability or swelling properties varied with the structure of excipients. For example, MgSt could improve the water uptake, while impeded tablet swelling. Furthermore, in the present study it is verified that tablet disintegration was closely related to these parameters, especially wetting rate and initial water absorption rate. The higher wetting rate of water on tablet or initial water absorption rate, the faster swelling it be, resulting in the shorter tablet disintegration time. The methods utilized in the present study were feasible and effective. The disintegration of tablets did relate to these parameters, especially wetting rate and initial water absorption rate.

Key acceptability attributes of orodispersible films.

PubMed

Scarpa, Mariagiovanna; Paudel, Amrit; Kloprogge, Frank; Hsiao, Wen Kai; Bresciani, Massimo; Gaisford, Simon; Orlu, Mine

2018-04-01

The features rendering orodispersible films (ODFs) patient-centric formulations are widely discussed in the scientific literature. However there is a lack of research studies exploring ODF characteristics with a potential impact on end-user acceptability. The aim of this study was to identify the key ODF characteristics affecting end-user acceptability by developing in vitro test methods for the prediction of ODFs acceptability and correlate these formulation characteristics with the data obtained from a human panel study. Four drug-free single-polymer films were prepared by solvent casting. Solutions of poly(vinyl) alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395 KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop methods were used to assess disintegration time. A human panel of 24 healthy young adults was employed to identify end-user acceptability criteria of the four study film samples. Texture analysis data of ODF tack were not found to be in agreement with the in vivo perceived stickiness in the mouth. However, measurement of the area under the adhesive force curve obtained by DMA correlated with in vivo perceived stickiness data for all samples. The disintegration times obtained by drop method were more comparable to human panel data than the petri dish method. Hence DMA and drop methods proved to be promising methodologies for the prediction of the end-user acceptability. The type and molecular weight of the film-forming polymer had a strong influence on stickiness perception, whereas only polymeric molecular weight influenced perceived disintegration time. The human panel study showed that Participant Reported Outcomes (PROs) for the perceived stickiness in the mouth and disintegration time of test films received significantly different scores between samples, and thus were identified as the key attributes with the potential to affect the end-user acceptability. ODF stickiness and disintegration time should therefore be evaluated at an early stage of the drug product design. Copyright © 2018 Elsevier B.V. All rights reserved.

The Ongoing Evolution of the K2-22 System

NASA Astrophysics Data System (ADS)

Colon, Knicole D.; Zhou, George; Shporer, Avi; Collins, Karen A.; Bieryla, Allyson; Latham, David W.; Espinoza, Nestor; Murgas, Felipe; Pattarakijwanich, Petchara; Awiphan, Supachai; TECH Collaboration

2018-06-01

Of the thousands of exoplanets known, only three disintegrating planets have been identified. These disintegrating planets appear to have tails of dusty material that produce asymmetric transit shapes. K2-22b is one of these few disintegrating planets discovered to date, and its light curve not only displays highly variable transit depths but also uniquely displays evidence of a leading dust tail. Here, we present results from a large ground-based photometric observing campaign of the K2-22 system that took place between December 2016 and May 2017, which we use to investigate the evolution of the transit of K2-22b. Last observed in early 2015, in these new observations we recover the transit around the expected time and measure a typical depth of <1%. We find that the transit depth has decreased compared to observations from 2014 and 2015, where the maximum transit depth measured at that time was ~1.3%. These new observations support ongoing variability in the transit depth, shape, and time of K2-22b, although the overall shallowness of the transit makes a detailed analysis of the transit shape and timing difficult. In addition, we find no strong evidence of wavelength-dependent transit depths for epochs where we have simultaneous coverage at multiple wavelengths. Given the observed decrease in the transit depth between 2015 and 2017, we encourage continued high-precision photometric monitoring of this system in order to further constrain the evolution timescale and to aid comparative studies with the other few disintegrating planets known.

Performance evaluation of a bipolar electrolysis/electrocoagulation (EL/EC) reactor to enhance the sludge dewaterability.

PubMed

Gharibi, Hamed; Sowlat, Mohammad Hossein; Mahvi, Amir Hossein; Keshavarz, Morteza; Safari, Mohammad Hossein; Lotfi, Saeedeh; Bahram Abadi, Mahnaz; Alijanzadeh, Azim

2013-01-01

The present study aimed to evaluate the performance of a bipolar electrolysis/electrocoagulation reactor designed to enhance the sludge dewaterability. The reactor was 15 L in volume, with two series of plates used in it; Ti/RuO(2) plates for the electrolysis of the sludge, and also aluminum and iron plates for electrocoagulation process. The dewaterability of the sludge was determined in terms of its capillary suction time (CST) and specific resistance to filtration (SRF), while the degree of sludge disintegration was determined based on the value of degree of sludge disintegration (DD(SCOD)). The maximum reduction in CST and SRF was observed at a detention time of 20 min and a voltage of 30 V. However, increasing of both detention time and voltage significantly increased the values of CST and SRF even to an extent that they both exceeded those of the untreated sludge. The optimal degree of sludge disintegration achieved by the present study was 2.5%, which was also achieved at a detention time of 20 min and a voltage of 30V. As reported previously, increased DD(SCOD) values led to increasing CST and SRF values, due primarily to the disruption of the sludge flocs. According to the results from the present study, it can be concluded that simultaneous application of electrocoagulation and electrolysis is effective in enhancing the sludge dewaterability, because electrocoagulation helps to achieve a higher degree of sludge disintegration while maintaining the desired sludge dewaterability. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reduction of excess sludge production using mechanical disintegration devices.

PubMed

Strünkmann, G W; Müller, J A; Albert, F; Schwedes, J

2006-01-01

The usability of mechanical disintegration techniques for the reduction of excess sludge production in the activated sludge process was investigated. Using three different disintegration devices (ultrasonic homogeniser, stirred media mill, high pressure homogeniser) and different operational parameters of the disintegration, the effect of mechanical disintegration on the excess sludge production and on the effluent quality was studied within a continuously operated, laboratory scale wastewater treatment system with pre-denitrification. Depending on the operational conditions and the disintegration device used, a reduction of excess sludge production of up to 70% was achieved. A combination of mechanical disintegration with a membrane bioreactor process with high sludge age is more energy effective concerning reduction of sludge production than with a conventional activated sludge process at lower sludge ages. Depending on the disintegration parameters, the disintegration has no, or only minor, negative effect on the soluble effluent COD and on the COD-removal capacity of the activated sludge process. Nitrogen-removal was slightly deteriorated by the disintegration, whereas the system used was not optimised for nitrogen removal before disintegration was implemented.

A comprehensive in vitro and in vivo evaluation of thiolated matrix tablets as a gastroretentive delivery system.

PubMed

Senyigit, Zeynep Ay; Vetter, Anja; Guneri, Tamer; Bernkop-Schnürch, Andreas

2011-08-01

The aim of this study was to investigate the potential of thiolated matrix tablets for gastroretentive delivery systems. Poly(acrylic acid)-cysteine (PAA-Cys) and chitosan-4-thiobuthylamidine (chitosan-TBA) were evaluated as anionic and cationic thiolated polymers and riboflavin was used as a model drug. Tablets were prepared by direct compression and each formulation was characterized in terms of disintegration, swelling, mucoadhesion, and drug release properties. Thereafter, the gastric residence times of tablets were determined with in vivo study in rats. The resulting PAA-Cys and chitosan-TBA conjugates displayed 172.80 ± 30.33 and 371.11 ± 72.74 µmol free thiol groups, respectively. Disintegration studies demonstrated the stability of thiolated tablets up to 24 h, whereas tablets prepared with unmodified PAA and chitosan disintegrated within a time period of 1 h. Mucoadhesion studies showed that mucoadhesion work of PAA-Cys and chitosan-TBA tablets were 1.341- and 2.139-times higher than unmodified ones. The mucoadhesion times of PAA, PAA-Cys, chitosan, and chitosan-TBA tablets were 1.5 ± 0.5, 21 ± 1, 1 ± 0.5, 17 ± 1 h, respectively. These results confirm the theory that thiol groups react with mucin glycoproteins and form covalent bonds to the mucus layer. Release studies indicated that a controlled release was provided with thiolated tablets up to 24 h. These promising in vitro results of thiolated tablets were proved with in vivo studies. The thiolated tablets showed a gastroretention time up to 6 h, whereas unmodified tablets completely disintegrated within 1 h in rat stomach. Consequently, the study suggests that thiolated matrix tablets might be promising formulations for gastroretentive delivery systems.

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.

[Effect of Food Thickeners on the Disintegration, Dissolution, and Drug Activity of Rapid Oral-disintegrating Tablets].

PubMed

Tomita, Takashi; Kohda, Yukinao; Kudo, Kenzo

2018-01-01

　For patients with dysphagia in medical facilities and nursing homes, food thickeners are routinely used to aid the ingestion of medicines such as tablets. However, some types of thickeners affect the disintegration and dissolution of tablets, such as rapidly-disintegrating magnesium oxide tablets and donepezil hydrochloride orally disintegrating tablets. Additionally, delayed disintegration and dissolution of tablets affect a drug's efficacy. As an example, with Voglibose orally disintegrating tablets, marked differences are observed in changes in glucose levels during glucose tolerance testing. When using food thickeners to aid tablet ingestion, it is therefore necessary to select a product that has little effect on drug disintegration, dissolution, and activity.

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.

Mechanical sludge disintegration for the production of carbon source for biological nutrient removal.

PubMed

Kampas, P; Parsons, S A; Pearce, P; Ledoux, S; Vale, P; Churchley, J; Cartmell, E

2007-04-01

The primary driver for a successful biological nutrient removal is the availability of suitable carbon source, mainly in the form of volatile fatty acids (VFA). Several methods have been examined to increase the amount of VFAs in wastewater. This study investigates the mechanism of mechanical disintegration of thickened surplus activated sludge by a deflaker technology for the production of organic matter. This equipment was able to increase the soluble carbon in terms of VFA and soluble chemical oxygen demand (SCOD) with the maximum concentration to be around 850 and 6530 mgl(-1), for VFA and SCOD, respectively. The particle size was reduced from 65.5 to 9.3 microm after 15 min of disintegration with the simultaneous release of proteins (1550 mgl(-1)) and carbohydrates (307 mgl(-1)) indicating floc disruption and breakage. High performance size exclusion chromatography investigated the disintegrated sludge and confirmed that the deflaker was able to destroy the flocs releasing polymeric substances that are typically found outside of cells. When long disintegration times were applied (>or=10 min or >or=9000 kJkg(-1)TS of specific energy) smaller molecular size materials were released to the liquid phase, which are considered to be found inside the cells indicating cell lysis.

Differing disintegration and dissolution rates, pharmacokinetic profiles and gastrointestinal tolerability of over the counter ibuprofen formulations.

PubMed

Bjarnason, Ingvar; Sancak, Ozgur; Crossley, Anne; Penrose, Andrew; Lanas, Angel

2018-02-01

Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter t max and a higher C max for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in C max . © 2017 Royal Pharmaceutical Society.

Evaluation of synthesized cross linked polyvinyl alcohol as potential disintegrant.

PubMed

Patel, Ashok R; Vavia, Pradeep R

2010-01-01

The present study deals with evaluation of crosslinked poly vinyl alcohol (PVA) as a potential disintegrant. Crosslinking of PVA was carried out using glutaraldehyde as a crosslinker, in presence of acidic conditions. The crosslinking reaction was optimized for a) polymer: crosslinker ratio; b) temperature requirement and c) reaction duration. Certain physical parameters of the disintegrant (including sedimentation volume, hydration capacity, specific surface area and bulk and tap density) were determined and compared to the known disintegrants. Characterization was carried out using FT-IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also studied for acute toxicity in rats and found to be safe for oral use. Disintegration property of formed product was compared to known disintegrant (Ac-Di-Sol) and it was found to give better results. The disintegration mechanism of developed disintegrant was postulated based on results obtained from various physical evaluations including: Study of effect of disintegrant concentration, fillers, and hardness, mode of incorporation and method of granulation on disintegration activity. By changing the condition parameters of well known crosslinking reaction of PVA, we obtained a crosslinked product which had excellent disintegration activity, good flow and optimal tableting properties.

Preformulation Studies of Selected Pretreatment and Therapeutic Compounds

DTIC Science & Technology

1982-07-01

Mefloquine Hydrochloride) Placebo Tablets 39 Manufacturing Formula 40 Final Weight Variation 42 Disintegration Test 43 In-Process Control Analyses 44...average "weight of 563.9 mg. Disintegration times in 900 ml of water (37°C) were around 35 seconds for six tablets , Each tablet had an average thickness...WGROS ( M an .va*. ohm It nseew M nev op ,adIpit 6p 6"Wee dmme6) Antimalarials; preformulations; antileishminiasie; capsule production; tablet

3D-micro-patterned fibrous dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2018-03-01

At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficulties associated with the unpredictable inter-particle interactions. Therefore, to achieve more predictable dosage form properties and processing, we have recently introduced melt-processed polymeric cellular dosage forms. The cellular forms disintegrated and released drug rapidly if the cells were predominantly interconnected. Preparation of interconnected cells, however, relies on the coalescence of gas bubbles in the melt, which is unpredictable. In the present work, therefore, new melt-processed fibrous dosage forms with contiguous void space are presented. The dosage forms are prepared by melt extrusion of the drug-excipient mixture followed by patterning the fibrous extrudate on a moving surface. It is demonstrated that the resulting fibrous structures are fully predictable by the extruder nozzle diameter and the motion of the surface. Furthermore, drug release experiments show that the disintegration time of the fibrous forms prepared in this work is of the order of that of the corresponding single fibers. The thin fibers of polyethylene glycol (excipient) and acetaminophen (drug) in turn disintegrate in a time proportional to the fiber radius and well within immediate-release specification. Finally, models of dosage form disintegration and drug release by single fibers and fibrous dosage forms are developed. It is found that drug release from fibrous forms is predictable by the physico-chemical properties of the excipient and such microstructural parameters as the fiber radius, the inter-fiber spacing, and the volume fraction of water-soluble excipient in the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

Endoscopic Assessment and Prediction of Prostate Urethral Disintegration After Histotripsy Treatment in a Canine Model*

PubMed Central

Schade, George R.; Styn, Nicholas R.; Hall, Timothy L.

2012-01-01

Abstract Background and Purpose Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration. Materials and Methods Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1–3/prostate ≥1 cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE. Results Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively. Conclusion Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking. PMID:22050511

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.

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.

Emulsions and rectal formulations containing myrrh essential oil for better patient compliance.

PubMed

Etman, M; Amin, M; Nada, A H; Shams-Eldin, M; Salama, O

2011-06-01

Myrrh has long been used for its circulatory, disinfectant, analgesic, antirheumatic, antidiabetic, and schistosomicidal properties. Myrrh essential oil (MEO) was extracted from the oleo-gum resin of Commiphora molmol and formulated into emulsions and suppositories to mask/avoid its bitter taste. Three oil-in-water emulsions (E1-E3) were formulated and taste was evaluated by 10 volunteers. Particle size distribution was measured and correlated with excipients and the method of preparation. Physical and chemical stability testing was carried out for the optimum formulation (E2). Seven suppository formulations were investigated (F1-F7). Suppocire AML (F1) and Suppocire CM (F2) were chosen as fatty bases, and polyethylene glycol (PEG) 1500 (F3), PEG 4000 (F4), and a PEG blend (50% PEG 6000 + 30% PEG 1500 + 20% PEG 400) (F5) were chosen as water-soluble bases. A blend of PEG 1500 and Suppocire CM was also used (F7). Camphor (5%) was added to PEG 1500 (F6). Disintegration time, release rate, DSC, fracture points, and weight uniformity were evaluated. The overall average bitterness for formulations E1, E2, and E3 was 6.44, 4.15, and 3.45, respectively. Suppositories containing Suppocire AML had the fastest disintegration time (1.5 min) with dissolution efficiency (DE) of 56.8%. F3 containing PEG 1500 had a fast disintegration time of 2.5 min and maximum DE of 93.5%. The PEG blend had satisfactory release: (DE = 90.9%). A mixed fatty and water-soluble base (F7) had a disintegration time of 5 min and low DE (33.4%). A stable MEO emulsion with acceptable taste was formulated to improve patient acceptance and compliance. F3 suppositories yielded satisfactory results, while formulations containing fatsoluble bases exhibited poor release.

[Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms].

PubMed

Watanabe, Yoshiteru; Mukai, Baku; Kawamura, Ken-ichi; Ishikawa, Tatsuya; Namiki, Michihiro; Utoguchi, Naoki; Fujii, Makiko

2002-02-01

In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristics could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500,000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet:aminophylline 50 mg, L-HPC and PEG 6000; outer shell:PH-102:PEG = 8:2 200 mg) with the timed-release characteristics was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristics in the gastrointestinal tract. The time (tmax) required to reach the maximum plasma theophylline concentration (Cmax) observed after administration of the press-coated tablet was significantly (p < 0.05) delayed compared with that observed after administration of aminophylline solution in the control experiment. However, there was no difference in Cmax and area under the plasma theophylline concentration-time curve (AUC0-->24) between the press-coated tablet and aminophylline solution. These results suggest that the press-coated aminophylline tablet (with the timed-release characteristic) offers a promising forms of theophylline chronotherapy for asthma.

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.

Expedited Development of Diphenhydramine Orally Disintegrating Tablet through Integrated Crystal and Particle Engineering.

PubMed

Wang, Chenguang; Hu, Shenye; Sun, Changquan Calvin

2017-10-02

A palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), was developed using an integrated crystal and particle engineering approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including fast in vivo disintegration, and acceptable bitterness and grittiness. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed using 15 g of DPH and in two months. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.

Effects of disintegration on anaerobic degradation of sewage excess sludge in downflow stationary fixed film digesters.

PubMed

Engelhart, M; Krüger, M; Kopp, J; Dichtl, N

2000-01-01

The effects of mechanical disintegration on anaerobic digestibility of sewage excess sludge in downflow stationary fixed film (DSFF) digesters were investigated on laboratory scale. Mechanical pretreatment using a high pressure homogenizer led to significantly enhanced concentrations of soluble proteins and carbohydrates in the feed sludge. Using DSFF digesters with two different tubular plastic media as support material it was shown that a stable digestion process could be achieved at hydraulic retention times (HRT) down to 5 days. Compared to conventional digesters at 10 d and 15 d HRT respectively, the degradation of volatile solids was enhanced up to 25%, also resulting in a higher specific biogas production. Further investigations on degradation of soluble proteins and carbohydrates showed that a slowly degradable fraction of carbohydrates was released via disintegration. Using the distribution of chain length and the concentrations of volatile fatty acids as process parameters, the dependability on the HRT and the degree of disintegration (the release of soluble COD) predominated the effects of specific surface area of the support media.

Ozone disintegration of excess biomass and application to nitrogen removal.

PubMed

Park, Ki Young; Lee, Jae Woo; Ahn, Kyu-Hong; Maeng, Sung Kyu; Hwang, Jong Hyuk; Song, Kyung-Guen

2004-01-01

A pilot-scale facility integrated with an ozonation unit was built to investigate the feasibility of using ozone-disintegration byproducts of wasted biomass as a carbon source for denitrification. Ozonation of biomass resulted in mass reduction by mineralization as well as by ozone-disintegrated biosolids recycling. Approximately 50% of wasted solids were recovered as available organic matter (ozonolysate), which included nonsettleable microparticles and soluble fractions. Microparticles were observed in abundance at relatively low levels of ozone doses, while soluble fractions became dominant at higher levels of ozone doses in ozone-disintegrated organics. Batch denitrification experiments showed that the ozonolysate could be used as a carbon source with a maximum denitrification rate of 3.66 mg nitrogen (N)/g volatile suspended solids (VSS) x h. Ozonolysate was also proven to enhance total nitrogen removal efficiency in the pilot-scale treatment facility. An optimal chemical oxygen demand (COD)-to-nitrogen ratio for complete denitrification was estimated as 5.13 g COD/g N. The nitrogen-removal performance of the modified intermittently decanted extended aeration process dependent on an external carbon supply could be described as a function of solids retention time.

Enhancement of the sludge disintegration and nutrients release by a treatment with potassium ferrate combined with an ultrasonic process.

PubMed

Li, Wei; Yu, Najiaowa; Liu, Qian; Li, Yiran; Ren, Nanqi; Xing, Defeng

2018-09-01

Sludge disintegration by ultrasound is a promising sludge treatment method. In order to enhance the efficiency of the sludge reduction and hydrolysis, potassium ferrate (K 2 FeO 4 ) (PF) was used. A novel method was developed to improve the sludge disintegration-sludge pretreatment by using PF in combination with an ultrasonic treatment (PF + ULT). After a short-term PF + ULT treatment, 17.23% of the volatile suspended solids (VSS) were reduced after a 900-min reaction time, which is 61.3% higher than the VSS reduction for the raw sludge. The supernatant soluble chemical oxygen demand (SCOD), total nitrogen (TN), volatile fatty acids (VFAs), soluble protein and polysaccharides increased by 522.5%, 1029.4%, 878.4%, 2996.6% and 801.9%, respectively. The constituent parts of the dissolved organic matter of the sludge products were released efficiently, which demonstrated the positive effect caused by the PF + ULT. The enhanced sludge disintegration process further alleviates environmental risk and offers a more efficient and convenient method for utilizing sludge. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro and in vivo correlation of disintegration and bitter taste masking using orally disintegrating tablet containing ion exchange resin-drug complex.

PubMed

Kim, Jong-Il; Cho, Sang-Min; Cui, Jing-Hao; Cao, Qing-Ri; Oh, Euichaul; Lee, Beom-Jin

2013-10-15

Although the taste-masking of bitter drug using ion exchange resin has been recognized, in vitro testing using an electronic tongue (e-Tongue) and in vivo bitterness test by human panel test was not fully understood. In case of orally disintegrating tablet (ODT) containing bitter medicine, in vitro and in vivo disintegration is also importance for dosage performance. Donepezil hydrochloride was chosen as a model drug due to its bitterness and requires rapid disintegration for the preparation of ODT. In this study, ion exchange resin drug complex (IRDC) at three different ratios (1:2, 1:1, 2:1) was prepared using a spray-drying method and then IRDC-loaded ODT containing superdisintegrants (crospovidone, croscarmellose sodium, and sodium starch glycolate) were prepared by the direct compression method. The physical properties and morphologies were then characterized by scanning electron microscopy (SEM), X-ray powder diffraction (PXRD) and electrophoretic laser scattering (ELS), respectively. The in vitro taste-masking efficiency was measured with an electronic tongue (e-Tongue). In vivo bitterness scale was also evaluated by human volunteers and then we defined new term, "bitterness index (BI)" to link in vitro e-Tongue. There was a good correlation of IRDC between in vitro e-Tongue values and in vivo BI. Furthermore, IRDC-loaded ODT showed good in vitro/in vivo correlation in the disintegration time. The optimal IRDC-loaded ODTs displayed similar drug release profiles to the reference tablet (Aricept(®) ODT) in release media of pH 1.2, pH 4.0, pH 6.8 and distilled water but had significantly better palatability in vivo taste-masking evaluation. The current IRDC-loaded ODT according to the in vitro and in vivo correlation of disintegration and bitter taste masking could provide platforms in ODT dosage formulations of donepezil hydrochloride for improved patient compliances. Copyright © 2013 Elsevier B.V. All rights reserved.

Theory of positive disintegration as a model of adolescent development.

PubMed

Laycraft, Krystyna

2011-01-01

This article introduces a conceptual model of the adolescent development based on the theory of positive disintegration combined with theory of self-organization. Dabrowski's theory of positive disintegration, which was created almost a half century ago, still attracts psychologists' and educators' attention, and is extensively applied into studies of gifted and talented people. The positive disintegration is the mental development described by the process of transition from lower to higher levels of mental life and stimulated by tension, inner conflict, and anxiety. This process can be modeled by a sequence of patterns of organization (attractors) as a developmental potential (a control parameter) changes. Three levels of disintegration (unilevel disintegration, spontaneous multilevel disintegration, and organized multilevel disintegration) are analyzed in detail and it is proposed that they represent behaviour of early, middle and late periods of adolescence. In the discussion, recent research on the adolescent brain development is included.

Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam

PubMed Central

Bala, Rajni; Khanna, Sushil; Pawar, Pravin

2014-01-01

Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of C max (95.87%), t max (71.42%), AUC0−t (98.125%), and AUC0−∞ (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles. PMID:25328709

Ultrasonic sludge disintegration for enhanced methane production in anaerobic digestion: effects of sludge hydrolysis efficiency and hydraulic retention time.

PubMed

Kim, Dong-Jin; Lee, Jonghak

2012-01-01

Hydrolysis of waste activated sludge (WAS) has been regarded as the rate limiting step of anaerobic sludge digestion. Therefore, in this study, the effect of ultrasound and hydraulic residence time during sludge hydrolysis was investigated with the goal of enhancing methane production from anaerobic digestion (AD). WAS was ultrasonically disintegrated for hydrolysis, and it was semi-continuously fed to an anaerobic digesters at various hydraulic retention times (HRTs). The results of these experiments showed that the solids and chemical oxygen demand (COD) removal efficiencies when using ultrasonically disintegrated sludge were higher during AD than the control sludge. The longer the HRT, the higher the removal efficiencies of solids and COD, while methane production increased with lower HRT. Sludge with 30% hydrolysis produced 7 × more methane production than the control sludge. The highest methane yields were 0.350 m(3)/kg volatile solids (VS)(add) and 0.301 m(3)/kg COD(con) for 16 and 30% hydrolyzed sludge, respectively. In addition, we found that excess ultrasound irradiation may inhibit AD since the 50% hydrolyzed sludge produced lower methane yields than 16 and 30% hydrolyzed sludge.

A simple and inexpensive image analysis technique to study the effect of disintegrants concentration and diluents type on disintegration.

PubMed

Berardi, Alberto; Bisharat, Lorina; Blaibleh, Anaheed; Pavoni, Lucia; Cespi, Marco

2018-06-20

Tablets disintegration is often the result of a size expansion of the tablets. In this study, we quantified the extent and direction of size expansion of tablets during disintegration, using readily available techniques, i.e. a digital camera and a public domain image analysis software. After validating the method, the influence of disintegrants concentration and diluents type on kinetics and mechanisms of disintegration were studied. Tablets containing diluent, disintegrant (sodium starch glycolate-SSG, crospovidone-PVPP or croscarmellose sodium-CCS) and lubricant were prepared by direct compression. Projected area and aspect ratio of the tablets were monitored using image analysis techniques. The developed method could describe the kinetics and mechanisms of disintegration qualitatively and quantitatively. SSG and PVPP acted purely by swelling and shape recovery mechanisms. Instead, CCS worked by a combination of both mechanisms, the extent of which changed depending on its concentration and the diluent type. We anticipate that the method described here could provide a framework for the routine screening of tablets disintegration using readily available equipment. Copyright © 2018. Published by Elsevier Inc.

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.

Disintegrating Comet 73P

NASA Astrophysics Data System (ADS)

Jewitt, David

2017-08-01

Disintegration may be the leading cause of the demise of cometary nuclei yet is rarely observed and not well understood. We propose to use an amazing but largely unpublished archival dataset on comet 73P/Schwassmann-Wachmann 3 from HST in order to characterize the breakup of this body, focussing on components 73-B, 73-C and 73-G from GO 8699, 10625 and 10992. We will measure the number, sizes, velocities and (short-term) photometric variability of the fragments in 73-B and 73-G and derive the ejection speeds and times. A nucleus/coma convolution model will be used to extract the best estimates of fragment and nucleus size. The size distributions and integral masses will be compared to the parent body masses to estimate lifetimes. Lightcurves will be determined to the test the possibility that disintegration is due to rotational instability.

Physical disintegration of toilet papers in wastewater systems: experimental analysis and mathematical modeling.

PubMed

Eren, Beytullah; Karadagli, Fatih

2012-03-06

Physical disintegration of representative toilet papers was investigated in this study to assess their disintegration potential in sewer systems. Characterization of toilet papers from different parts of the world indicated two main categories as premium and average quality. Physical disintegration experiments were conducted with representative products from each category according to standard protocols with improvements. The experimental results were simulated by mathematical model to estimate best-fit values of disintegration rate coefficients and fractional distribution ratios. Our results from mathematical modeling and experimental work show that premium products release more amounts of small fibers and disintegrate more slowly than average ones. Comparison of the toilet papers with the tampon applicators studied previously indicates that premium quality toilet papers present significant potential to persist in sewer pipes. Comparison of turbulence level in our experimental setup with those of partial flow conditions in sewer pipes indicates that drains and small sewer pipes are critical sections where disintegration of toilet papers will be limited. For improvement, requirements for minimum pipe slopes may be increased to sustain transport and disintegration of flushable products in small pipes. In parallel, toilet papers can be improved to disintegrate rapidly in sewer systems, while they meet consumer expectations.

Development of aprepitant loaded orally disintegrating films for enhanced pharmacokinetic performance.

PubMed

Sharma, Radhika; Kamboj, Sunil; Singh, Gursharan; Rana, Vikas

2016-03-10

The present investigation was aimed to prepare orally disintegrating films (ODFs) containing aprepitant (APT), an antiemetic drug employing pullulan as film forming agent, tamarind pectin as wetting agent and liquid glucose as plasticizer and solubiliser. The ODFs were prepared using solvent casting method. The method was optimized employing 3(2) full factorial design considering proportion of pullulan: tamarind pectin and concentration of liquid glucose as independent variables and disintegration time, wetting time, folding endurance, tensile strength and extensibility as dependent variables. The optimized ODF was evaluated for various physicochemical, mechanical, drug release kinetics and bioavailability studies. The results suggested prepared film has uniform film surface, non-sticky and disintegrated within 18s. The in-vitro release kinetics revealed more than 87% aprepitant was released from optimized ODF as compared to 85%, 49%, and 12% aprepitant release from marketed formulation Aprecap, micronized aprepitant and non micronized aprepitant, respectively. The results of animal preference study indicated that developed aprepitant loaded ODFs are accepted by rabbits as food material. Animal pharmacokinetic (PK) study showed 1.80, 1.56 and 1.36 fold enhancement in relative bioavailability for aprepitant loaded ODF, Aprecap and micronized aprepitant respectively, in comparison with non-micronized aprepitant. Overall, the solubilised aprepitant when incorporated in the form of aprepitant loaded ODF showed enhanced bioavailability as compared to micronized/non-micronized aprepitant based oral formulations. These findings suggested that aprepitant loaded ODF could be effective for antiemesis during cancer chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

[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.

[Ultrasonic sludge treatment and its application on aerobic digestion].

PubMed

Li, Huan; Jin, Yi-ying; Nie, Yong-feng; Li, Lei; Yang, Hai-ying

2007-07-01

In order to enhance the degradation efficiency of waste activated sludge (WAS) in conventional aerobic digestion, various ultrasonic assisted treatment methods were investigated including ultrasonic disintegration of influent sludge, ultrasonic improvement of influent sludge activity and ultrasonic disintegration of return sludge. Firstly the effects of ultrasonic sludge treatment were studied to choose appropriate ultrasonic parameters, and then the experiments of aerobic digestion with different ultrasonic treatments were carried out. The results show that 1.0 W/mL, 10 minutes ultrasonic treatment can increase soluble chemical oxygen demand (SCOD) in the supernatant phase of sludge sample by 5.4 times and decrease total suspended solid (TSS) by 16%; 0.05 W/mL, 10 min ultrasonic treatment can increase the specific oxygen uptake rate (SOUR) of sludge sample by 29%. The two kinds of ultrasonic influent sludge pretreatment can't improve aerobic digestion effectively. Ultrasonic return sludge disintegration can enhance the volatile suspended solid (VSS) degradation ratio by 15%. Furthermore, the settlement performance of digested sludge is still good and the pollutant concentrations of supernatant phase increase slightly. So ultrasonic return sludge disintegration is considered as the most appropriate assisted treatment mode for aerobic digestion.

Food-dependent disintegration of immediate release fosamprenavir tablets: in vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system.

PubMed

Brouwers, Joachim; Anneveld, Bart; Goudappel, Gert-Jan; Duchateau, Guus; Annaert, Pieter; Augustijns, Patrick; Zeijdner, Evelijn

2011-02-01

In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with the nutritional drink Scandishake Mix® in the stomach compartment of TIM-1, simulating the fed state, disintegration and fosamprenavir dissolution were significantly postponed compared to the fasted state (lag time 80 ± 23 min). This resulted in a lag in the appearance of bioaccessible fosamprenavir (<5% during the first 2h), even though the nutritional state did not significantly alter the cumulative bioaccessibility after 5h. These results were in agreement with the previously observed postprandial delay in gastric fosamprenavir tablet disintegration and subsequent amprenavir absorption in healthy volunteers. Therefore, TIM-1 can be used in tablet development to identify food-induced disintegration issues causing unexpected clinical behavior. From a mechanistic perspective, we applied MRI to illustrate impaired water ingress in fosamprenavir tablets immersed in the nutritional drink compared to simulated gastric fluid. This effect may be attributed to both competition between nutritional components and the tablet for the available water (indicated by reduced rotational and translational diffusion) as well as the possible formation of a food-dependent precipitation layer on the HPMC-coated tablet. Copyright © 2010 Elsevier B.V. All rights reserved.

A model stomach system to investigate disintegration kinetics of solid foods during gastric digestion.

PubMed

Kong, F; Singh, R P

2008-06-01

Knowledge of the disintegration kinetics of food particulates in the human stomach is essential for assessing the bioaccessibility of nutrients in solid foods and understanding stomach emptying. The objective of this study was to develop a model stomach system and to investigate the kinetics of food disintegration. Our system consisted mainly of a turntable and a jacketed glass chamber containing simulated gastric juice in which plastic beads were added to simulate food particulates as well as provide a suitable mechanical destructive force on food samples. The mechanical force on the samples was simultaneously measured using the load cell of a TA-XT2 texture analyzer. Cylindrical carrots and ham samples were used as representative foods. The system is capable of simulating the in vivo stomach in terms of providing a wide range of continuous and periodic forces comparable to those measured in vivo. The modified power exponential function of the form y(t)= 1 - (1 -e(-kt))(beta), where y(t) is the mass retention ratio at time t, provided a reasonable description for the disintegration performance of tested foods. The mass retention curve can be either a sigmoidal decay with an initial delay or an exponential decay, which are decided largely by the hardness of the foods during digestion and the extent of physical force acting on the foods. A good match was observed between the kinetics of food disintegration and in vivo stomach emptying.

[Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase. Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).

Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

PubMed

Blaesi, Aron H; Saka, Nannaji

2017-11-01

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug in the walls. Copyright © 2017 Elsevier B.V. All rights reserved.

Mild disintegration of the green microalgae Chlorella vulgaris using bead milling.

PubMed

Postma, P R; Miron, T L; Olivieri, G; Barbosa, M J; Wijffels, R H; Eppink, M H M

2015-05-01

In this work, the mild disintegration of the microalgae Chlorella vulgaris for the release of intracellular products has been studied. By means of bead milling the microalgae suspensions were successfully disintegrated at different biomass concentrations (25-145 gDW kg(-1)) over a range of agitator speeds (6-12 m s(-1)). In all cases over 97% of cell disintegration was achieved resulting in a release of water soluble proteins. A clear optimum rate of disintegration and protein release was observed at an agitator speed of 9-10 m s(-1) regardless of the biomass concentration. Selective extraction of water soluble proteins was observed as proteins released sooner than cell disintegration took place. Proteins could be released at 85% lower energy input than for cell disintegration resulting in specific energy consumptions well below 2.5 kWh kgDW(-1). Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of turbulence on the disintegration rate of flushable consumer products.

PubMed

Karadagli, Fatih; Rittmann, Bruce E; McAvoy, Drew C; Richardson, John E

2012-05-01

A previously developed model for the physical disintegration of flushable consumer products is expanded by investigating the effects of turbulence on the rate of physical disintegration. Disintegration experiments were conducted with cardboard tampon applicators at 100, 150, and 200 rotations per minute, corresponding to Reynold's numbers of 25,900, 39,400, and 52,900, respectively, which were estimated by using computational fluid dynamics modeling. The experiments were simulated with the disintegration model to obtain best-fit values of the kinetic and distribution parameters. Computed rate coefficients (ki) for all solid sizes (i.e., greater than 8, 4 to 8, 2 to 4, and 1 to 2 mm) increased strongly with Reynold's number or rotational speed. Thus, turbulence strongly affected the disintegration rate of flushable products, and the relationship of the ki values to Reynold's number can be included in mathematical representations of physical disintegration.

Effects of ultrasonic disintegration of excess sludge obtained in disintegrators of different constructions.

PubMed

Zielewicz, Ewa; Tytła, Malwina

2015-01-01

The ultrasonic disintegration of excess sludge is placed after the mechanical thickening but before the digestion tanks in order to intensify the process of sludge stabilization. The effects obtained directly after ultrasonic disintegration depend on many factors and can be grouped in two main categories: factors affecting the quality of sludge and those associated with the construction of disintegrators and its parameters. The ultrasonic disintegration research was carried out using three types of structural solutions of disintegrators. Two of them, that is, WK-2000 ultrasonic generator (P = 400 W) working with a thin sonotrode and WK-2010 ultrasonic generator (P = 100-1000 W) working with a new type construction emitter lens sonotrode, were compared with the influence of a washer with a flat emitter. The investigations have shown that in the same sludge, using the same value of volumetric energy, the resulting effect depends on the construction of the ultrasonic disintegrator, that is, design of the head and the ratio between the field of the emitter and the field of the chamber in sonicated medium.

Critical operational parameters for zero sludge production in biological wastewater treatment processes combined with sludge disintegration.

PubMed

Yoon, Seong-Hoon; Lee, Sangho

2005-09-01

Mathematical models were developed to elucidate the relationships among process control parameters and the effect of these parameters on the performance of anoxic/oxic biological wastewater processes combined with sludge disintegrators (A/O-SD). The model equations were also applied for analyses of activated sludge processes hybrid with sludge disintegrators (AS-SD). Solubilization ratio of sludge in the sludge disintegrator, alpha, hardly affected sludge reduction efficiencies if the biomass was completely destructed to smaller particulates. On the other hand, conversion efficiency of non-biodegradable particulates to biodegradable particulates, beta, significantly affected sludge reduction efficiencies because beta was directly related to the accumulation of non-biodegradable particulates in bioreactors. When 30% of sludge in the oxic tank was disintegrated everyday and beta was 0.5, sludge reduction was expected to be 78% and 69% for the A/O-SD and AS-SD processes, respectively. Under this condition, the sludge disintegration number (SDN), which is the amount of sludge disintegrated divided by the reduced sludge, was calculated to be around 4. Due to the sludge disintegration, live biomass concentration decreased while other non-biodegradable particulates concentration increased. As a consequence, the real F/M ratio was expected to be much higher than the apparent F/M. The effluent COD was maintained almost constant for the range of sludge disintegration rate considered in this study. Nitrogen removal efficiencies of the A/O-SD process was hardly affected by the sludge disintegration until daily sludge disintegration reaches 40% of sludge in the oxic tank. Above this level of sludge disintegration, autotrophic biomass concentration decreases overly and TKN in the effluent increases abruptly in both the A/O-SD and AS-SD processes. Overall, the trends of sludge reduction and effluent quality according to operation parameters matched well with experimental results found in literatures.

Formulation and Evaluation of New Glimepiride Sublingual Tablets.

PubMed

Al-Madhagi, Wafa; Abdulbari Albarakani, Ahmed; Khaled Alhag, Abobakr; Ahmed Saeed, Zakaria; Mansour Noman, Nahlah; Mohamed, Khaldon

2017-01-01

Oral mucosal delivery of drugs promotes rapid absorption and high bioavailability, with a subsequent immediate onset of pharmacological effect. However, many oral mucosal deliveries are compromised by the possibility of the patient swallowing the active substance before it has been released and absorbed locally into the systemic circulation. The aim of this research was to introduce a new glimepiride formula for sublingual administration and rapid drug absorption that can be used in an emergency. The new sublingual formulation was prepared after five trials to prepare the suitable formulation. Two accepted formulations of the new sublingual product were prepared, but one of them with disintegration time of 1.45 min and searching for preferred formulation, the binder, is changed with Flulac and starch slurry to prepare formula with disintegration time of 21 seconds that supports the aim of research to be used in an emergency. The five formulations were done, after adjusting to the binder as Flulac and aerosil with disintegration time of 21 seconds and accepted hardness as well as the weight variation. The assay of a new product (subglimepiride) is 103% which is a promising result, confirming that the formula succeeded. The new product (subglimepiride) is accepted in most quality control tests and it is ready for marketing.

Electrochemical pretreatment of waste activated sludge: effect of process conditions on sludge disintegration degree and methane production.

PubMed

Ye, Caihong; Yuan, Haiping; Dai, Xiaohu; Lou, Ziyang; Zhu, Nanwen

2016-11-01

Waste activated sludge (WAS) requires a long digestion time because of a rate-limiting hydrolysis step - the first phase of anaerobic digestion (AD). Pretreatment can be used prior to AD to facilitate the hydrolysis step and improve the efficiency of WAS digestion. This study evaluated a novel application of electrochemical (EC) technology employed as the pretreatment method prior to AD of WAS, focusing on the effect of process conditions on sludge disintegration and subsequent AD process. A superior process condition of EC pretreatment was obtained by reaction time of 30 min, electrolysis voltage of 20 V, and electrode distance of 5 cm, under which the disintegration degree of WAS ranged between 9.02% and 9.72%. In the subsequent batch AD tests, 206 mL/g volatile solid (VS) methane production in EC pretreated sludge was obtained, which was 20.47% higher than that of unpretreated sludge. The AD time was 19 days shorter for EC pretreated sludge compared to the unpretreated sludge. Additionally, the EC + AD reactor achieved 41.84% of VS removal at the end of AD. The analysis of energy consumption showed that EC pretreatment could be effective in enhancing sludge AD with reduced energy consumption when compared to other pretreatment methods.

Drug-beta-cyclodextrin containing pellets prepared with a high-shear mixer.

PubMed

Gainotti, Alessandro; Bettini, Ruggero; Gazzaniga, Andrea; Colombo, Paolo; Giordano, Ferdinando

2004-01-01

This work was aimed at investigating the preparation of beta-cyclodextrin-microcrystalline cellulose pellets by means of a high-shear mixer, both in the absence or in the presence of ibuprofen as model drug. Drug loading of pellets was accomplished by means of two alternative techniques: 1) solution layering or 2) powder layering. The prepared pellets were characterised in terms of size distribution, shape factor, friability and dissolution rate. The interaction between ibuprofen and beta-cyclodextrin was monitored by Differential Scanning Calorimetry (DSC). Micro Fourier Transform Infrared spectroscopy (MicroFTIR) was applied to determine the distribution of components within each pellet on a micro scale. Pellets with narrow size distribution and containing up to about 90% of BCD were prepared using water as binder. The process yield resulted around 84 and 63% for drug-free and medicate pellets respectively. Drug loaded pellets with favourable technological and biopharmaceutical characteristics can be obtained both by powder or solution layering techniques. The latter proved to be more suitable for producing pellets with high drug contents, reduced friability and high drug dissolution rates.

Optimization of poorly compactable drug tablets manufactured by direct compression using the mixture experimental design.

PubMed

Martinello, Tiago; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Taqueda, Maria Elena Santos; Consiglieri, Vladi O

2006-09-28

The poor flowability and bad compressibility characteristics of paracetamol are well known. As a result, the production of paracetamol tablets is almost exclusively by wet granulation, a disadvantageous method when compared to direct compression. The development of a new tablet formulation is still based on a large number of experiments and often relies merely on the experience of the analyst. The purpose of this study was to apply experimental design methodology (DOE) to the development and optimization of tablet formulations containing high amounts of paracetamol (more than 70%) and manufactured by direct compression. Nineteen formulations, screened by DOE methodology, were produced with different proportions of Microcel 102, Kollydon VA 64, Flowlac, Kollydon CL 30, PEG 4000, Aerosil, and magnesium stearate. Tablet properties, except friability, were in accordance with the USP 28th ed. requirements. These results were used to generate plots for optimization, mainly for friability. The physical-chemical data found from the optimized formulation were very close to those from the regression analysis, demonstrating that the mixture project is a great tool for the research and development of new formulations.

Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

PubMed

Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

2008-05-01

Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer transit time in the semisupine position relative to the erect position. There was a statistically significant difference in transit time among the 3 types of tablets (P = 0.007), with the Novopharm tablet (HR = 0.59; P < 0.001) and Teva tablet (HR = 0.71; P = 0.042) having longer transit times compared with the risedronate tablet. In 4 instances, the Novopharm tablet disintegrated and dispersed in the esophagus, once in the erect position and 3 times in the semisupine position. In these healthy female subjects, esophageal transit was delayed when the tablets were given in the semisupine position. The branded risedronate tablet had a significantly faster transit time than the 2 generic formulations of alendronate tested.

Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

PubMed

Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

2017-07-01

This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k d . Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI 95% ) revealed significant differences between k d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f 2 ) test. The final relationship between k d and k perm was found to be hyperbolic, signifying the initial effect of k perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k d and k perm . The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

Childhood Disintegrative Disorder as a Complication of Chicken Pox.

PubMed

Verma, Jitendra Kumar; Mohapatra, Satyakam

2016-01-01

Childhood disintegrative disorder (CDD) is characterized by late onset (>3 years of age) of developmental delays in language, social function and motor skills. Commonly there is no antecedent physical disorder leading to childhood disintegrative disorder. The present case report describes a child who developed childhood disintegrative disorder at the age of 6 years after an episode of chicken pox.

Intensification of anaerobic digestion efficiency with use of mechanical excess sludge disintegration in the context of increased energy production in wastewater treatment plants

NASA Astrophysics Data System (ADS)

Żubrowska-Sudoł, Monika; Podedworna, Jolanta; Bisak, Agnieszka; Sytek-Szmeichel, Katarzyna; Krawczyk, Piotr; Garlicka, Agnieszka

2017-11-01

The main goal of the study was to evaluate the effects of mechanical sludge disintegration for enhancing full scale anaerobic digestion of municipal sludge. Batch disintegration tests and lab dewatering tests were also performed aiming at determining the release of organic compounds and assessing the impact of disintegration of excess sludge before the fermentation process of mixed sludge on the dewaterability of post-fermented sludge, respectively. In the study a disc disintegrator driven by a motor with a power of 30 kW, revolutions n = 2950 rpm has been used. It was shown that with increase of energy consumed in the disintegration, the increased amounts of organic compounds were released from the sludge. It was also documented that the introduction of the excess sludge disintegration prior to fermentation tank, resulted in a significant increase in biogas production (by an average of 33.9%) and in increase in volatile total solids reduction in the fermented sludge (by an average of 22.7%). Moreover, the obtained results indicate the possibility of obtaining a higher degree of sludge dewatering, which was subjected to anaerobic stabilization with using disintegrated excess sludge.

Biological disintegration of microalgae for biomethane recovery-prediction of biodegradability and computation of energy balance.

PubMed

Kavitha, S; Yukesh Kannah, R; Rajesh Banu, J; Kaliappan, S; Johnson, M

2017-11-01

The present study investigates the synergistic effect of combined bacterial disintegration on mixed microalgal biomass for energy efficient biomethane generation. The rate of microalgal biomass lysis, enhanced biodegradability, and methane generation were used as indices to assess efficiency of the disintegration. A maximal dissolvable organics release and algal biomass lysis rate of about 1100, 950 and 800mg/L and 26, 23 and 18% was achieved in PA+C (protease, amylase+cellulase secreting bacteria), C (cellulase alone) and PA (protease, amylase) microalgal disintegration. During anaerobic fermentation, a greater production of volatile fatty acids (1000mg/L) was noted in PA+C bacterial disintegration of microalgal biomass. PA+C bacterial disintegration improve the amenability of microalgal biomass to biomethanation process with higher biodegradability of about 0.27gCOD/gCOD, respectively. The energy balance analysis of this combined bacterial disintegration of microalgal biomass provides surplus positive net energy (1.14GJ/d) by compensating the input energy requirements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantitative measurement of marginal disintegration of ceramic inlays.

PubMed

Hayashi, Mikako; Tsubakimoto, Yuko; Takeshige, Fumio; Ebisu, Shigeyuki

2004-01-01

The objectives of this study include establishing a method for quantitative measurement of marginal change in ceramic inlays and clarifying their marginal disintegration in vivo. An accurate CCD optical laser scanner system was used for morphological measurement of the marginal change of ceramic inlays. The accuracy of the CCD measurement was assessed by comparing it with microscopic measurement. Replicas of 15 premolars restored with Class II ceramic inlays at the time of placement and eight years after restoration were used for morphological measurement by means of the CCD laser scanner system. Occlusal surfaces of the restored teeth were scanned and cross-sections of marginal areas were computed with software. Marginal change was defined as the area enclosed by two profiles obtained by superimposing two cross-sections of the same location at two different times and expressing the maximum depth and mean area of the area enclosed. The accuracy of this method of measurement was 4.3 +/- 3.2 microm in distance and 2.0 +/- 0.6% in area. Quantitative marginal changes for the eight-year period were 10 x 10 microm in depth and 50 x 10(3) microm2 in area at the functional cusp area and 7 x 10 microm in depth and 28 x 10(3) microm2 in area at the non-functional cusp area. Marginal disintegration at the functional cusp area was significantly greater than at the non-functional cusp area (Wilcoxon signed-ranks test, p < 0.05). This study constitutes a quantitative measurement of in vivo deterioration in marginal adaptation of ceramic inlays and indicates that occlusal force may accelerate marginal disintegration.

Mechanisms and kinetics models for ultrasonic waste activated sludge disintegration.

PubMed

Wang, Fen; Wang, Yong; Ji, Min

2005-08-31

Ultrasonic energy can be applied as pre-treatment to disintegrate sludge flocs and disrupt bacterial cells' walls, and the hydrolysis can be improved, so that the rate of sludge digestion and methane production is improved. In this paper, by adding NaHCO3 to mask the oxidizing effect of OH, the mechanisms of disintegration are investigated. In addition, kinetics models for ultrasonic sludge disintegration are established by applying multi-variable linear regression method. It has been found that hydro-mechanical shear forces predominantly responsible for the disintegration, and the contribution of oxidizing effect of OH increases with the amount of the ultrasonic density and ultrasonic intensity. It has also been inferred from the kinetics model which dependent variable is SCOD+ that both sludge pH and sludge concentration significantly affect the disintegration.

Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

PubMed

Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

2017-01-01

Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

Fast releasing oral electrospun PVP/CD nanofiber mats of taste-masked meloxicam.

PubMed

Samprasit, Wipada; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Kaomongkolgit, Ruchadaporn; Opanasopit, Praneet

2015-06-20

Fast release and taste masking of meloxicam (MX)-loaded polyvinylpyrrolidone (PVP)/cyclodextrin (CD) nanofiber mats were developed using an electrospinning process. CDs were blended to improve the stability of the mats. The morphology and diameter of the mats were determined using scanning electron microscopy (SEM); physical and mechanical properties were also studied. The MX content, disintegration time, MX release and cytotoxicity of the mats were investigated. In vivo studies were also performed in healthy human volunteers. The results indicated that the mats were successfully prepared with fiber in the nanometer range. MX was well incorporated into the mats, with an amorphous form. The mats showed suitable tensile strength. CDs improved the physical stability by their cage-like supramolecular structure to protect from humidity and moisture, and create bead free nanofiber mats. The nanofiber mats with CDs were physically stable without any hygroscopicity and fusion. A fast disintegration and release of MX was achieved. Moreover, this mat released MX faster than the MX powder and commercial tablets. The cytotoxicity test revealed that mats were safe for a 5-min incubation. The disintegration studies indicated that in vivo disintegration agreed with the in vitro studies; the mat rapidly disintegrated in the mouth. The less bitter of MX was occurred in the mats that incorporated CD, menthol and aspartame. In addition, this mat was physical stable for 6 months. The results suggest that these mats may be a good candidate for fast dissolving drug delivery systems of bitter drugs to increase the palatability of dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlation of dissolution and disintegration results for an immediate-release tablet.

PubMed

Nickerson, Beverly; Kong, Angela; Gerst, Paul; Kao, Shangming

2018-02-20

The drug release rate of a rapidly dissolving immediate-release tablet formulation with a highly soluble drug is proposed to be controlled by the disintegration rate of the tablet. Disintegration and dissolution test methods used to evaluate the tablets were shown to discriminate manufacturing process differences and compositionally variant tablets. In addition, a correlation was established between disintegration and dissolution. In accordance with ICH Q6A, this work demonstrates that disintegration in lieu of dissolution is suitable as the drug product quality control method for evaluating this drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

Adversity, time, and well-being: A longitudinal analysis of time perspective in adulthood.

PubMed

Holman, E Alison; Silver, Roxane Cohen; Mogle, Jacqueline A; Scott, Stacey B

2016-09-01

Despite the prominence of time in influential aging theories and the ubiquity of stress across the life span, research addressing how time perspective (TP) and adversity are associated with well-being across adulthood is rare. Examining the role of TP in coping with life events over the life span would be best accomplished after large-scale population-based exposure to a specific event, with repeated assessments to examine within- and between-person differences over time. A national sample aged 18-91 years (N = 722, M = 49.4 years) was followed for 3 years after the September 11, 2001 (9/11) terrorist attacks. Respondents completed assessments of 9/11-related television (TV) exposure 9-21 days after the attacks, temporal disintegration 2 months post-9/11, and TP, ongoing stress, and well-being at 12, 24, and 36 months post-9/11. Results provided support for measurement invariance of TP across time and across age. Early 9/11-related TV exposure was significantly associated with greater temporal disintegration. Temporal disintegration and ongoing stress, in turn, were associated with between- and within-person variation in past TP. This effect was qualified by an age interaction that indicated a stronger relationship between ongoing stress and past TP for younger compared with older adults. Past and future TP were significantly and independently related to individual differences and within-person variation in psychological well-being, regardless of age. Future work should incorporate adversity as an important correlate of TP across adulthood. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

PubMed

Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

2017-03-01

A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

Disintegration of the agricultural by-product wheat bran under subcritical conditions.

PubMed

Reisinger, Michael; Tirpanalan, Özge; Pruksasri, Suwattana; Kneifel, Wolfgang; Novalin, Senad

2018-02-10

The disintegration of destarched wheat bran in water and sulfuric acid (pH 3) under subcritical conditions (275-300 °C) and at short reaction times (1-4 min) was investigated. A cascade process comprising a stepwise separation of the liquid was applied to reduce the formation of undesired degradation products. The highest degree of biomass disintegration (67% dry mass solubilization) was achieved by application of a cascade process at 275 °C (pH 3). Regarding the dissolution of carbohydrates (monomeric and oligomeric form), the total glucose yields remained below 60%, while the total xylose and arabinose yields were about 76% and 67%. Approximately 74% of the protein and 95% of the mineral fraction could be extracted. The application of the cascade process enabled a substantially reduced formation of degradation products. When operating hydrothermally and subcritically in order to avoid some problematic aspects of a biorefinery, an extensive disintegration and monomerization of wheat bran and its constituents remains difficult even under the tested conditions (300 °C, pH 3). However, the applied cascade process proved to be useful to increase the yields and to substantially reduce the formation of undesired degradation products. Despite this fact, increased water consumption has to be conceded. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Capsule shell material impacts the in vitro disintegration and dissolution behaviour of a green tea extract☆

PubMed Central

Glube, Natalie; Moos, Lea von; Duchateau, Guus

2013-01-01

Purpose In vitro disintegration and dissolution are routine methods used to assess the performance and quality of oral dosage forms. The purpose of the current work was to determine the potential for interaction between capsule shell material and a green tea extract and the impact it can have on the release. Methods A green tea extract was formulated into simple powder-in-capsule formulations of which the capsule shell material was either of gelatin or HPMC origin. The disintegration times were determined together with the dissolution profiles in compendial and biorelevant media. Results All formulations disintegrated within 30 min, meeting the USP criteria for botanical formulations. An immediate release dissolution profile was achieved for gelatin capsules in all media but not for the specified HPMC formulations. Dissolution release was especially impaired for HPMCgell at pH 1.2 and for both HPMC formulations in FeSSIF media suggesting the potential for food interactions. Conclusions The delayed release from studied HPMC capsule materials is likely attributed to an interaction between the catechins, the major constituents of the green tea extract, and the capsule shell material. An assessment of in vitro dissolution is recommended prior to the release of a dietary supplement or clinical trial investigational product to ensure efficacy. PMID:25755998

Capsule shell material impacts the in vitro disintegration and dissolution behaviour of a green tea extract.

PubMed

Glube, Natalie; Moos, Lea von; Duchateau, Guus

2013-01-01

In vitro disintegration and dissolution are routine methods used to assess the performance and quality of oral dosage forms. The purpose of the current work was to determine the potential for interaction between capsule shell material and a green tea extract and the impact it can have on the release. A green tea extract was formulated into simple powder-in-capsule formulations of which the capsule shell material was either of gelatin or HPMC origin. The disintegration times were determined together with the dissolution profiles in compendial and biorelevant media. All formulations disintegrated within 30 min, meeting the USP criteria for botanical formulations. An immediate release dissolution profile was achieved for gelatin capsules in all media but not for the specified HPMC formulations. Dissolution release was especially impaired for HPMCgell at pH 1.2 and for both HPMC formulations in FeSSIF media suggesting the potential for food interactions. The delayed release from studied HPMC capsule materials is likely attributed to an interaction between the catechins, the major constituents of the green tea extract, and the capsule shell material. An assessment of in vitro dissolution is recommended prior to the release of a dietary supplement or clinical trial investigational product to ensure efficacy.

Effect of moisture sorption on the performance of crospovidone.

PubMed

Hiew, Tze Ning; Johan, Nur Atiqah Binte; Desai, Parind Mahendrakumar; Chua, Siang Meng; Loh, Zhi Hui; Heng, Paul Wan Sia

2016-11-30

Crospovidone is a commonly used tablet disintegrant. However, the synthetic disintegrant has been known to be hygroscopic and high moisture content in crospovidone used could exert deleterious effects on tablets formulated with it. The objective of this study was to elicit a better understanding between crospovidone-water interaction and its effect on disintegrant performance. Moisture sorption and desorption isotherms were obtained together with the enthalpy of immersion. Crospovidone samples stored at four relative humidities were used to formulate tablets and the resultant tablets were evaluated for their mechanical, dimensional and disintegratability attributes. Analyses of the moisture sorption isotherms indicated that externally adsorbed moisture accounted for the bulk of the total moisture content in crospovidone, with minimal amount of moisture absorbed intramolecularly. Enthalpy of immersion became less exothermic with crospovidone samples stored at increasing storage humidity. Correspondingly, improvement in disintegration time became less pronounced. This was postulated to be a consequence of premature wetting of the particle surfaces by externally adsorbed moisture. High humidity was also detrimental to tablet hardness and thickness. In conclusion, the impact of moisture sorption during storage by excipients such as crospovidone could be better understood by the appreciation of crospovidone-water interaction and its consequence on tablet quality. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of ultrasonic disintegration of excess sewage sludge.

PubMed

Zielewicz, Ewa

2016-10-01

Breaking down sludge floc (sonodyspergation effect) and destruction of the cell membranes of microorganisms forming floc is a direct effect of ultrasonic disintegration of sludge excess. This results in release of organic material by liquid sludge (the sonolysis effect). Desired technological effects of the disintegration are: to shorten the hydrolytic phase of fermentation, to increase the production of biogas (source of renewable energy) and an increased mineralization (stability) of fermented sludge. The presented study demonstrates research covering thickened excess sludge of various physicochemical properties, collected from nine municipal sewage treatment plants. The sludge was subjected to ultrasonic disintegration using three differently constructed disintegrators and different proportions of sonification area. Direct effects of disintegration were monitored and recorded using selected indicators describing changes in the properties of sludge and increase of substance dispersed and dissolved in the supernatant liquid to be filtered. Studies have demonstrated that those (direct) effects of ultrasonic disintegration depend on the physicochemical properties of the sludge (foremost the concentration of dry solids) that determine their variable susceptibility to the disintegration methods. The direct effects also depend on optimal process conditions (which consist of the construction of the ultrasonic disintegrator), the geometric proportions of the sonication area and the operating parameters of disintegration (which could be appropriately matched to the characteristics of sludge). The most preferable results were obtained for ultrasonic disintegration of sludge with a dry matter concentration C 0 < 4.2 %. The highest effect of sonolysis-an almost 30-fold increase in the COD dissolved in the supernatant-was obtained for the sludge of lowest dry matter (C 0 = 2.0 %), which was sonicated in a reactor with a short transducer of the largest radiating surface area, as well as the lowest ratio between this area and area of reactor. The best effects of disagglomeration of flocks have corresponded with the high value of power density U UD = 880-900 WL(-1).

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

PubMed

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

PubMed Central

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible. PMID:28442890

Disintegration of excess activated sludge--evaluation and experience of full-scale applications.

PubMed

Zábranská, J; Dohányos, M; Jenícek, P; Kutil, J

2006-01-01

Anaerobic digestion of sewage sludge can be improved by introducing a disintegration of excess activated sludge as a pretreatment process. The disintegration brings a deeper degradation of organic matter and less amount of output sludge for disposal, a higher production of biogas and consequently energy yield, in some cases suppression of digesters foaming and better dewaterability. The full-scale application of disintegration by a lysate-thickening centrifuge was monitored long term in three different WWTPs. The evaluation of contribution of disintegration to biogas production and digested sludge quality was assessed and operational experience is discussed. Increment of specific biogas production was evaluated in the range of 15-26%, organic matter in digested sludge significantly decreased to 48-49%. Results proved that the installation of a disintegrating centrifuge in WWTPs of different sizes and conditions would be useful and beneficial.

IHF-independent assembly of the Tn10 strand transfer transpososome: implications for inhibition of disintegration.

PubMed

Stewart, Barry J; Wardle, Simon J; Haniford, David B

2002-08-15

The frequency of DNA transposition in transposition systems that employ a strand transfer step may be significantly affected by the occurrence of a disintegration reaction, a reaction that reverses the strand transfer event. We have asked whether disintegration occurs in the Tn10 transposition system. We show that disintegration substrates (substrates constituting one half of the strand transfer product) are assembled into a transpososome that mimics the strand transfer intermediate. This strand transfer transpososome (STT) does appear to support an intermolecular disintegration reaction, but only at a very low level. Strikingly, assembly of the STT is not dependent on IHF, a host protein that is required for de novo assembly of all previously characterized Tn10 transpososomes. We suggest that disintegration substrates are able to form both transposon end and target type contacts with transposase because of their enhanced conformational flexibility. This probably allows the conformation of DNA within the complex that prevents the destructive disintegration reaction, and is responsible for relaxing the DNA sequence requirements for STT formation relative to other Tn10 transpososomes.

IHF-independent assembly of the Tn10 strand transfer transpososome: implications for inhibition of disintegration

PubMed Central

Stewart, Barry J.; Wardle, Simon J.; Haniford, David B.

2002-01-01

The frequency of DNA transposition in transposition systems that employ a strand transfer step may be significantly affected by the occurrence of a disintegration reaction, a reaction that reverses the strand transfer event. We have asked whether disintegration occurs in the Tn10 transposition system. We show that disintegration substrates (substrates constituting one half of the strand transfer product) are assembled into a transpososome that mimics the strand transfer intermediate. This strand transfer transpososome (STT) does appear to support an intermolecular disintegration reaction, but only at a very low level. Strikingly, assembly of the STT is not dependent on IHF, a host protein that is required for de novo assembly of all previously characterized Tn10 transpososomes. We suggest that disintegration substrates are able to form both transposon end and target type contacts with transposase because of their enhanced conformational flexibility. This probably allows the conformation of DNA within the complex that prevents the destructive disintegration reaction, and is responsible for relaxing the DNA sequence requirements for STT formation relative to other Tn10 transpososomes. PMID:12169640

Sewage sludge disintegration by high-pressure homogenization: a sludge disintegration model.

PubMed

Zhang, Yuxuan; Zhang, Panyue; Ma, Boqiang; Wu, Hao; Zhang, Sheng; Xu, Xin

2012-01-01

High-pressure homogenization (HPH) technology was applied as a pretreatment to disintegrate sewage sludge. The effects of homogenization pressure, homogenization cycle number, and total solid content on sludge disintegration were investigated. The sludge disintegration degree (DD(COD)), protein concentration, and polysaccharide concentration increased with the increase of homogenization pressure and homogenization cycle number, and decreased with the increase of sludge total solid (TS) content. The maximum DD(COD) of 43.94% was achieved at 80 MPa with four homogenization cycles for a 9.58 g/L TS sludge sample. A HPH sludge disintegration model of DD(COD) = kNaPb was established by multivariable linear regression to quantify the effects of homogenization parameters. The homogenization cycle exponent a and homogenization pressure exponent b were 0.4763 and 0.7324 respectively, showing that the effect of homogenization pressure (P) was more significant than that of homogenization cycle number (N). The value of the rate constant k decreased with the increase of sludge total solid content. The specific energy consumption increased with the increment of sludge disintegration efficiency. Lower specific energy consumption was required for higher total solid content sludge.

Minnesota retrofit insulation in situ test program

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

Not Available

1978-06-01

The use of cellulose, glass fiber, rock/slag fiber and urea formaldehyde installed as retrofit insulation materials in residential walls and ceilings was studied. Homes were selected for testing according to the type of retrofit insulation, age of retrofit insulation and whether the retrofit was in the wall or ceiling. The total project was comprised of 22 wall and 48 ceiling samples. Samples of retrofit insulation were taken from an area of three to four square feet in the ceiling or wall of the home. The sample volume was measured, the sample removed and double-sealed in polyethylene bags. The samples weremore » shipped to the laboratory for testing. Laboratory measurements were made of density, moisture content, thermal resistance, and relative flammability of each sample. Additionally, the friability and compressive strength of each urea-formaldehyde foam sample was measured. The following results were obtained. Cellulosic loose fill insulation tests indicated that settling and moisture build-up are not serious problems. Flammability is a concern. Age did not affect the properties of the cellulosic loose fill, but fungal growth was evident. Shrinkage, ranging from 2.5 to 9 percent, averaging 4.5 percent, was exhibited. Degradation of the foam samples with time did not occur. Density was the most critical property affecting the other properties. The higher the density, the higher the thermal resistence per inch, the lower the friability and the higher the compressive strength. The accurate prediction of the fiber diameter, amount of unfiberized mineral, and extent of modular clumping thermal resistance of loose fill mineral fiber insulations is related to and is not solely a factor of density. The materials in this sample did not noticeably affect the structure or wiring of the retrofitted homes. (LCL)« less

Optical and magnetic properties of porous anodic alumina/Ni nanocomposite films

NASA Astrophysics Data System (ADS)

Zhang, Jing-Jing; Li, Zi-Yue; Zhang, Zhi-Jun; Wu, Tian-Shan; Sun, Hui-Yuan

2013-06-01

A simple method to tune the optical properties of porous anodic alumina (PAA) films embedded with Ni is reported. The films display highly saturated colors after being synthesized by an ac electrodeposition method. The optical properties of the samples can be effectively tuned by varying the oxidation time of aluminum. The ultrashort Ni nanowires (100 nm long and 50 nm in diameter) present only fcc phase and show no apparent averaged effective magnetic anisotropy. The coercivity mechanism of the Ni nanowires in our case is consistent with fanning mechanism based on a chain-of-spheres model. PAA/Ni films with structural color and magnetic properties have friability-resistant feature and can be used in many areas, including decoration, display, and multifunctional anti-counterfeiting technology.

Childhood disintegrative disorder: distinction from autistic disorder and predictors of outcome.

PubMed

Rosman, N Paul; Bergia, Berta M

2013-12-01

Childhood disintegrative disorder, a rare, relentlessly progressive neurologic disorder, first described by Heller in 1908, remains a condition of great interest. It has long been debated whether it is a discrete disorder or simply a late-onset variant of childhood autism. We have studied 6 cases of childhood disintegrative disorder, collected over 8 years, and followed for 2.5 to 22 years (mean 8.6 years). Childhood disintegrative disorder begins later in life than autism, and following a period of entirely normal development; the regression is more global and more severe than in autism; seizures are more frequent than in autism, yet demonstrable organicity in childhood disintegrative disorder is decidedly rare. Lastly, the prognosis is usually much worse than in autism, but in those cases with neither seizures nor epileptiform activity on electroencephalography (EEG), the outcome may be more favorable. Childhood disintegrative disorder should be viewed as a condition distinct from childhood autism.

A new method for assessment of the sludge disintegration degree with the use of differential centrifugal sedimentation.

PubMed

Silvestri, Daniele; Wacławek, Stanisław; Gončuková, Zuzanna; Padil, Vinod V T; Grübel, Klaudiusz; Černík, Miroslav

2018-05-24

A novel method for assessing the disintegration degree (DD) of waste activated sludge (WAS) with the use of differential centrifugal sedimentation method (DCS) was shown herein. The method was validated for a WAS sample at four levels of disintegration in the range of 14.4-82.6% corresponding to the median particle size range of 8.5-1.6 µm. From the several sludge disintegration methods used (i.e. microwave, alkalization, ultrasounds and peroxydisulfate activated by ultrasounds), the activated peroxydisulfate disintegration resulted in the greatest DD 83% and the smallest median particle size of WAS. Particle size distribution of pretreated sludge, measured by DCS, was in a negative correlation with the DD, determined from soluble chemical oxygen demand (SCOD; determination coefficient of 0.995). Based on the obtained results, it may be concluded that the DCS analysis can approximate the WAS disintegration degree.

A Review of Disintegration Mechanisms and Measurement Techniques.

PubMed

Markl, Daniel; Zeitler, J Axel

2017-05-01

Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

Approach of describing dynamic production of volatile fatty acids from sludge alkaline fermentation.

PubMed

Wang, Dongbo; Liu, Yiwen; Ngo, Huu Hao; Zhang, Chang; Yang, Qi; Peng, Lai; He, Dandan; Zeng, Guangming; Li, Xiaoming; Ni, Bing-Jie

2017-08-01

In this work, a mathematical model was developed to describe the dynamics of fermentation products in sludge alkaline fermentation systems for the first time. In this model, the impacts of alkaline fermentation on sludge disintegration, hydrolysis, acidogenesis, acetogenesis, and methanogenesis processes are specifically considered for describing the high-level formation of fermentation products. The model proposed successfully reproduced the experimental data obtained from five independent sludge alkaline fermentation studies. The modeling results showed that alkaline fermentation largely facilitated the disintegration, acidogenesis, and acetogenesis processes and severely inhibited methanogenesis process. With the pH increase from 7.0 to 10.0, the disintegration, acidogenesis, and acetogenesis processes respectively increased by 53%, 1030%, and 30% while methane production decreased by 3800%. However, no substantial effect on hydrolysis process was found. The model also indicated that the pathway of acetoclastic methanogenesis was more severely inhibited by alkaline condition than that of hydrogentrophic methanogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disintegration of rocks based on magnetically isolated high voltage discharge

NASA Astrophysics Data System (ADS)

He, Mengbing; Jiang, Jinbo; Huang, Guoliang; Liu, Jun; Li, Chengzu

2013-02-01

Recently, a method utilizing pulsed power technology for disintegration of rocks arouses great interest of many researchers. In this paper, an improved method based on magnetic switch and the results shown that the uniform dielectrics like plastic can be broken down in water is presented, and the feasible mechanism explaining the breakdown of solid is proposed and proved experimentally. A high voltage pulse of 120 kV, rise time 0.2 μs was used to ignite the discharging channel in solids. When the plasma channel is formed in the solid, the resistance of the channel is quiet small; even if a relatively low voltage is applied on the channel on this occasion, it will produce high current to heat the plasma channel rapidly, and eventually disintegrate the solids. The feasibility of promising industrial application in the drilling and demolition of natural and artificial solid materials by the method we presented is verified by the experiment result in the paper.

Disintegration of rocks based on magnetically isolated high voltage discharge.

PubMed

He, Mengbing; Jiang, Jinbo; Huang, Guoliang; Liu, Jun; Li, Chengzu

2013-02-01

Recently, a method utilizing pulsed power technology for disintegration of rocks arouses great interest of many researchers. In this paper, an improved method based on magnetic switch and the results shown that the uniform dielectrics like plastic can be broken down in water is presented, and the feasible mechanism explaining the breakdown of solid is proposed and proved experimentally. A high voltage pulse of 120 kV, rise time 0.2 μs was used to ignite the discharging channel in solids. When the plasma channel is formed in the solid, the resistance of the channel is quiet small; even if a relatively low voltage is applied on the channel on this occasion, it will produce high current to heat the plasma channel rapidly, and eventually disintegrate the solids. The feasibility of promising industrial application in the drilling and demolition of natural and artificial solid materials by the method we presented is verified by the experiment result in the paper.

New test of Lorentz symmetry using ultrahigh-energy cosmic rays

NASA Astrophysics Data System (ADS)

Anchordoqui, Luis A.; Soriano, Jorge F.

2018-02-01

We propose an innovative test of Lorentz symmetry by observing pairs of simultaneous parallel extensive air showers produced by the fragments of ultrahigh-energy cosmic ray nuclei which disintegrated in collisions with solar photons. We show that the search for a cross-correlation of showers in arrival time and direction becomes background free for an angular scale ≲3 ° and a time window O (10 s ) . We also show that if the solar photo-disintegration probability of helium is O (10-5.5) then the hunt for spatiotemporal coincident showers could be within range of existing cosmic ray facilities, such as the Pierre Auger Observatory. We demonstrate that the actual observation of a few events can be used to constrain Lorentz violating dispersion relations of the nucleon.

Leaching of indium from obsolete liquid crystal displays: Comparing grinding with electrical disintegration in context of LCA

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

Dodbiba, Gjergj, E-mail: dodbiba@sys.t.u-tokyo.ac.jp; Nagai, Hiroki; Wang Lipang

2012-10-15

Highlights: Black-Right-Pointing-Pointer Two pre-treatment methods, prior to leaching of indium from obsolete LCD modules, were described. Black-Right-Pointing-Pointer Conventional grinding and electrical disintegration have been evaluated and compared in the context of LCA. Black-Right-Pointing-Pointer Experimental data on the leaching capacity for indium and the electricity consumption of equipment were inputted into the LCA model in order to compare the environmental performance of each method. Black-Right-Pointing-Pointer An estimate for the environmental performance was calculated as the sum of six impact categories. Black-Right-Pointing-Pointer Electrical disintegration method outperforms conventional grinding in all impact categories. - Abstract: In order to develop an effective recycling systemmore » for obsolete Liquid Crystal Displays (LCDs), which would enable both the leaching of indium (In) and the recovery of a pure glass fraction for recycling, an effective liberation or size-reduction method would be an important pre-treatment step. Therefore, in this study, two different types of liberation methods: (1) conventional grinding, and (2) electrical disintegration have been tested and evaluated in the context of Life Cycle Assessment (LCA). In other words, the above-mentioned methods were compared in order to find out the one that ensures the highest leaching capacity for indium, as well as the lowest environmental burden. One of the main findings of this study was that the electrical disintegration was the most effective liberation method, since it fully liberated the indium containing-layer, ensuring a leaching capacity of 968.5 mg-In/kg-LCD. In turn, the estimate for the environmental burden was approximately five times smaller when compared with the conventional grinding.« less

Current opinions and recommendations of paediatric healthcare professionals – The importance of tablets: Emerging orally disintegrating versus traditional tablets

PubMed Central

Alyami, Hamad; Koner, Jasdip; Terry, David; Mohammed, Afzal R.

2018-01-01

The appropriate prescribing of paediatric dosage forms is paramount in providing the desired therapeutic effect alongside successful medication adherence with the paediatric population. Often it is the opinion of the healthcare practitioner that dictates which type of dosage form would be most appropriate for the paediatric patient, with liquids being both the most commonly available and most commonly used. Orally disintegrating tablets (ODTs) are an emerging dosage form which provide many benefits over traditional dosage forms for paediatric patients, such as rapid disintegration within the oral cavity, and the reduction in the risk of choking. However the opinion and professional use of healthcare practitioners regarding ODT’s is not known. This study was designed to assess the opinions of several types of healthcare professionals (n = 41) regarding ODTs, using a survey across two hospital sites. Results reaffirmed the popularity of liquids for prescribing in paediatrics, with 58.0% of participants preferring this dosage form. ODTs emerged as the second most popular dosage form (30.0%), with healthcare practitioners indicating an increasing popularity amongst patients in the hospital setting, belief with 63.0% of practitioners agreeing that many liquid formulations could be substituted with a suitable ODT. The desired properties of an ideal ODT were also identified by healthcare practitioners preferring a small, fast disintegrating tablet (90.2% and 95.1% respectively), with the taste, disintegration time and flavour being the three most important attributes identified (29.5%, 28.7% and 21.7% respectively). This study provided a pragmatic approach in assessing healthcare professional’s opinions on ODTs, highlighting the ideas and thoughts of practitioners who are on the frontline of paediatric prescribing and treatment and gave an indication to their preference for ODT properties. PMID:29489871

Galahad Redux: An Assessment of the Disintegration of Merrill’s Marauders

DTIC Science & Technology

1975-06-06

Disintegration of Merrill’s Marauders 00 »m^ John B. Gaither, MAJ, USA » >«^ U.S. Army Command and General Staff College fQ Fort lieavenworth... Disintegration of Merrill’s Marauders 5 TYPE OF REPORT » PERIOD COVERED Final report 6 Jun 75 6 PERFORMING ORG. REPORT NUMBER 7. AUTHORC...analyze the disintegration of Merrill’s Marauders, by emphasizing the intangible, subjective factors present in the leadership environment. The

Correlation of Phosphorus Cross-Linking to Hydration Rates in Sodium Starch Glycolate Tablet Disintegrants Using MRI.

PubMed

Abraham, Anuji; Olusanmi, Dolapo; Ilott, Andrew J; Good, David; Murphy, Denette; Mcnamara, Daniel; Jerschow, Alexej; Mantri, Rao V

2016-06-01

Understanding the behavior of tablet disintegrants is valuable in the development of pharmaceutical solid dosage formulations. In this study, high-resolution magnetic resonance imaging has been used to understand the hydration behavior of a series of commercial sodium starch glycolate (SSG) samples, providing robust estimates of tablet disintegration rate that could be correlated with physicochemical properties of the SSGs, such as the extent of phosphorus (P) cross-linking as obtained from infra-red spectroscopy. Furthermore, elemental analysis together with powder X-ray diffraction has been used to quantify the presence of carboxymethyl groups and salt impurities, which also contribute to the disintegration behavior. The utility of Fast Low Angle SHot magnetic resonance imaging has been demonstrated as an approach to rapidly acquire approximations of the volume of a disintegrating tablet and, together with a robust voxel analysis routine, extract tablet disintegration rates. In this manner, a complete characterization of a series of SSG grades from different sources has been performed, showing the variability in their physicochemical properties and demonstrating a correlation between their disintegration rates and intrinsic characteristics. The insights obtained will be a valuable aid in the choice of disintegrant source as well as in managing SSG variability to ensure robustness of drug products containing SSG. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effects of chemical sludge disintegration on the performances of wastewater treatment by membrane bioreactor.

PubMed

Oh, Young-Khee; Lee, Ki-Ryong; Ko, Kwang-Baik; Yeom, Ick-Tae

2007-06-01

A new wastewater treatment process combining a membrane bioreactor (MBR) with chemical sludge disintegration was tested in bench scale experiments. In particular, the effects of the disintegration treatment on the excess sludge production in MBR were investigated. Two MBRs were operated. In one reactor, a part of the mixed liquor was treated with NaOH and ozone gas consecutively and was returned to the bioreactor. The flow rate of the sludge disintegration stream was 1.5% of the influent flow rate. During the 200 days of operation, the MLSS level in the bioreactor with the disintegration treatment was maintained relatively constant at the range of 10,000-11,000 mg/L while it increased steadily up to 25,000 mg/L in the absence of the treatment. In the MBR with the sludge disintegration, relatively constant transmembrane pressures (TMPs) could be maintained for more than 6 months while the MBR without disintegration showed an abrupt increase of TMP in the later phase of the operation. In conclusion, a complete control of excess sludge production in the membrane-coupled bioreactor was possible without significant deterioration of the treated water quality and membrane performances.

Model test of anchoring effect on zonal disintegration in deep surrounding rock masses.

PubMed

Chen, Xu-Guang; Zhang, Qiang-Yong; Wang, Yuan; Liu, De-Jun; Zhang, Ning

2013-01-01

The deep rock masses show a different mechanical behavior compared with the shallow rock masses. They are classified into alternating fractured and intact zones during the excavation, which is known as zonal disintegration. Such phenomenon is a great disaster and will induce the different excavation and anchoring methodology. In this study, a 3D geomechanics model test was conducted to research the anchoring effect of zonal disintegration. The model was constructed with anchoring in a half and nonanchoring in the other half, to compare with each other. The optical extensometer and optical sensor were adopted to measure the displacement and strain changing law in the model test. The displacement laws of the deep surrounding rocks were obtained and found to be nonmonotonic versus the distance to the periphery. Zonal disintegration occurs in the area without anchoring and did not occur in the model under anchoring condition. By contrasting the phenomenon, the anchor effect of restraining zonal disintegration was revealed. And the formation condition of zonal disintegration was decided. In the procedure of tunnel excavation, the anchor strain was found to be alternation in tension and compression. It indicates that anchor will show the nonmonotonic law during suppressing the zonal disintegration.

Model Test of Anchoring Effect on Zonal Disintegration in Deep Surrounding Rock Masses

PubMed Central

Chen, Xu-Guang; Zhang, Qiang-Yong; Wang, Yuan; Liu, De-Jun; Zhang, Ning

2013-01-01

The deep rock masses show a different mechanical behavior compared with the shallow rock masses. They are classified into alternating fractured and intact zones during the excavation, which is known as zonal disintegration. Such phenomenon is a great disaster and will induce the different excavation and anchoring methodology. In this study, a 3D geomechanics model test was conducted to research the anchoring effect of zonal disintegration. The model was constructed with anchoring in a half and nonanchoring in the other half, to compare with each other. The optical extensometer and optical sensor were adopted to measure the displacement and strain changing law in the model test. The displacement laws of the deep surrounding rocks were obtained and found to be nonmonotonic versus the distance to the periphery. Zonal disintegration occurs in the area without anchoring and did not occur in the model under anchoring condition. By contrasting the phenomenon, the anchor effect of restraining zonal disintegration was revealed. And the formation condition of zonal disintegration was decided. In the procedure of tunnel excavation, the anchor strain was found to be alternation in tension and compression. It indicates that anchor will show the nonmonotonic law during suppressing the zonal disintegration. PMID:23997683

Mechanisms of palatal epithelial seam disintegration by Transforming Growth Factor (TGF)-β3

PubMed Central

Ahmed, Shaheen; Liu, Chang-Chih; Nawshad, Ali

2007-01-01

TGFβ3 signaling initiates and completes sequential phases of cellular differentiation that is required for complete disintegration of the palatal medial edge seam, that progresses between 14 to 17 embryonic days in the murine system, which is necessary in establishing confluence of the palatal stroma. Understanding the cellular mechanism of palatal MES disintegration in response to TGFβ3 signaling will result in new approaches to defining the causes of cleft palate and other facial clefts that may result from failure of seam disintegration. We have isolated MES primary cells to study the details of MES disintegration mechanism by TGFβ3 during palate development using several biochemical and genetic approaches. Our results demonstrate a novel mechanism of MES disintegration where MES, independently yet sequentially, undergoes cell cycle arrest, cell migration and apoptosis to generate immaculate palatal confluency during palatogenesis in response to robust TGFβ3 signaling. The results contribute to a missing fundamental element to our base knowledge of the diverse roles of TGFβ3 in functional and morphological changes that MES undergo during palatal seam disintegration. We believe that our findings will lead to more effective treatment of facial clefting. PMID:17698055

Appendix A: Specimen 72275 documentation

NASA Technical Reports Server (NTRS)

Marvin, U. B.

1974-01-01

The friability of the matrix of specimen 72275 caused numerous fragments and an abundance of fines to break away from the main mass during transport from the moon and handling in the lunar receiving laboratory. Samples 72275,1 to 72275,14 were labeled during PET examination. Samples 72275,1, 4, 6, 7, 8, and 9 were placed in storage, and the remainder were distributed.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

PubMed Central

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant. PMID:28368030

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.

PubMed

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-03

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

NASA Astrophysics Data System (ADS)

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Characterization of fine abrasive particles for optical fabrication

NASA Astrophysics Data System (ADS)

Funkenbusch, Paul D.; Zhou, Y. Y.; Takahashi, Toshio; Quesnel, David J.; Lambropoulos, John C.

1995-08-01

Material removal during fine grinding operations is accomplished primarily by the action of individual abrasive particles on the glass surface. The mechanical properties of the abrasive are therefore important. Unfortunately it is difficult to directly measure the mechanical response of abrasives once they reach the scale of approximately 10 microns. As a result mechanical properties of fine abrasives are sometimes characterized in terms of an empirical `friability', based on the response of the abrasive to crushing by a metal ball in a vial. In this paper we report on modeling/experiments designed to more precisely quantify the mechanical properties of fine abrasives and ultimately to relate them to the conditions experienced by bound particles during grinding. Experiments have been performed on various types and sizes of diamond abrasives. The response of the particles is a strong function of the loading conditions and can be tracked by changing the testing parameters. Diamond size is also found to play a critical role, with finer diamonds less susceptible to fracture. A micromechanical model from the literature is employed estimate the forces likely to be seen during testing. We are also developing dynamic models to better predict the forces experienced during `friability' testing as a function of the testing parameters.

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.

Biological sludge solubilisation for reduction of excess sludge production in wastewater treatment process.

PubMed

Yamaguchi, T; Yao, Y; Kihara, Y

2006-01-01

A novel sludge disintegration system (JFE-SD system) was developed for the reduction of excess sludge production in wastewater treatment plants. Chemical and biological treatments were applied to disintegrate excess sludge. At the first step, to enhance biological disintegration, the sludge was pretreated with alkali. At the second step, the sludge was disintegrated by biological treatment. Many kinds of sludge degrading microorganisms integrated the sludge. The efficiency of the new sludge disintegration system was confirmed in a full-scale experiment. The JFE-SD system reduced excess sludge production by approximately 50% during the experimental period. The quality of effluent was kept at quite a good level. Economic analysis revealed that this system could significantly decrease the excess sludge treatment cost.

Disintegration of a Liquid Jet

NASA Technical Reports Server (NTRS)

Haenlein, A

1932-01-01

This report presents an experimental determination of the process of disintegration and atomization in its simplest form, and the influence of the physical properties of the liquid to be atomized on the disintegration of the jet. Particular attention was paid to the investigation of the process of atomization.

10 CFR 30.4 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... that amount of radioactive material which disintegrates at the rate of 37 billion atoms per second... material which disintegrates at the rate of 37 thousand atoms per second; Millicurie means that amount of radioactive material which disintegrates at the rate of 37 million atoms per second; Particle accelerator...

Effect of NaCl induced floc disruption on biological disintegration of sludge for enhanced biogas production.

PubMed

Kavitha, S; Kaliappan, S; Adish Kumar, S; Yeom, Ick Tae; Rajesh Banu, J

2015-09-01

In the present study, the influence of NaCl mediated bacterial disintegration of waste activated sludge (WAS) was evaluated in terms of disintegration and biodegradability of WAS. Floc disruption was efficient at 0.03 g/g SS of NaCl, promoting the shifts of extracellular proteins and carbohydrates from inner layers to extractable--soluble layers (90 mg/L), respectively. Outcomes of sludge disintegration reveal that the maximum solubilization achieved was found to be 23%, respectively. The model elucidating the parameter evaluation, explicates that floc disrupted--bacterially disintegrated sludge (S3) showed superior biodegradability of about 0.23 (gCOD/gCOD) than the bacterially disintegrated (S2) and control (S3) sludges of about 0.13 (gCOD/gCOD) and 0.05 (gCOD/gCOD), respectively. Cost evaluation of the present study affords net profits of approximately 2.5 USD and -21.5 USD in S3 and S2 sludge. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Disintegration of visible light-cured composite resins caused by long-term water immersion].

PubMed

Hino, T; Arai, K

1989-05-01

The purpose of this study is to clarify a cause of disintegration of composite resins by long-term immersion in distilled water. Three kinds of visible light-cured composite resins (Heliosit, Plurafil Super and Visio Dispers) and one conventional composite resin (Clearfil F II) were prepared as the specimens with a 20 mm diameter and 1 mm thickness. These specimens were immersed in distilled water at 37 +/- 1 degree C for 3 years. These specimens were analysed and observed by a comprehensive multi analyzer and scanning electron microscope. The other hand residues in distilled water were analysed by infrared (IR) and nuclear magnetic resonance (NMR) spectrometers. The surface layer of all four composite resins showed signs of disintegration. The composite resins with abundant dissolved substances had disintegrated markedly, and such disintegration occurred deep inside the specimens. In IR and 1H-NMR spectra of dissolved substances, two visible light-cured composite resins (Heliosit and Plurafil Super) could be detected unreacted monomers, but one visible light-cured composite resin (Visio Dispers) and one conventional composite resin (Clearfil F II) could not be detected them. In 1H-NMR spectra of dissolved substances of all four composite resins, new signals not composed originally were observed. The progress of disintegration were demonstrated clearly. The dissolved substances were shown as the disintegrated substance between resin matrixs and silane coupling agents. It is suggested that the disintegration of composite resins by long-term water immersion is derived from hydrolysis.

Role of the His-Cys finger of Moloney murine leukemia virus integrase protein in integration and disintegration.

PubMed Central

Jonsson, C B; Roth, M J

1993-01-01

Retroviral integrases mediate site-specific endonuclease and transesterification reactions in the absence of exogenous energy. The basis for the sequence specificity in these integrase-viral DNA recognition processes is unknown. Structural analogs of the disintegration substrate were made to analyze the disintegration reaction mechanism for the Moloney murine leukemia virus (M-MuLV) integrase (IN). Modifications in the target DNA portion of the disintegration substrate decreased enzymatic activity, while substitution of the highly conserved CA in the viral long terminal repeat portion had no effect on activity. The role of the His-Cys finger region in catalysis was addressed by N-ethylmaleimide (NEM) modification of the cysteine residues of M-MuLV IN as well as by mutations. Both integration activities, 3' processing, and strand transfer, were completely inhibited by NEM modification of M-MuLV IN, while disintegration activity was only partially sensitive. However, structural analogs of the disintegration substrates that were modified in the target DNA and had the conserved CA removed were not active with NEM-treated M-MuLV IN. In addition, mutants made in the His-Cys region of M-MuLV IN were examined and found to also be completely blocked in integration but not disintegration activity. These data suggest that the domains of M-MuLV IN that are required for the forward integration reaction substrate differ from those required for the reverse disintegration reaction substrate. Images PMID:8350412

Childhood Disintegrative Disorder: Issues for DSM-IV.

ERIC Educational Resources Information Center

Volkmar, Fred R.

1992-01-01

This paper presents evidence regarding the validity of the diagnostic concept of "autistic-like" childhood disintegrative disorder, also known as Heller syndrome or as disintegrative psychosis. Its inclusion in the DSM-IV (Diagnostic and Statistical Manual) is supported, and proposed criteria and narrative description are provided.…

Carbon source recovery from excess sludge by mechanical disintegration for biological denitrification.

PubMed

Zubrowska-Sudol, M

2018-04-01

The goal of the study was to evaluate the possibility of carbon source recovery from excess sludge by mechanical disintegration for biological denitrification. The total efficiency of denitrification, unit demand for organic compounds for denitrification, unit volume of disintegrated sludge and unit cost of nitrogen removal as a function of energy density used for excess sludge disintegration (70, 140 and 210 kJ/L) were analyzed. In the study a full-scale disc disintegrator was used (motor power: 30 kWh, motor speed: 2,950 rpm). It was shown that the amounts of organic compounds released from the activated sludge flocs at all tested levels of energy density are high enough to be used to intensify the removal of nitrogen compounds from wastewater. It was also documented that the energy density provided during process of disintegration was an important factor determining the characteristics of organic compounds obtained under the disintegration for their use in order to intensify the process of denitrification. The highest value of total efficiency of denitrification (50.5 ± 3.1 mg N/L) was obtained for carbon source recovery from excess sludge at 70 kJ/L, but the lowest unit cost of nitrogen removal occurred for 140 kJ/L (0.0019 ± 0.0011 EUR/g N).

Coordinated disintegration reactions mediated by Moloney murine leukemia virus integrase.

PubMed Central

Donzella, G A; Jonsson, C B; Roth, M J

1996-01-01

The protein-DNA and protein-protein interactions important for function of the integrase (IN) protein of Moloney murine leukemia virus (M-MuLV) were investigated by using a coordinated-disintegration assay. A panel of M-MuLV IN mutants and substrate alterations highlighted distinctions between the intermolecular and intramolecular reactions of coordinated disintegration. Mispairing of the crossbone single-strand region and altered long terminal repeat (LTR) positioning affected the intermolecular, but not the intramolecular, reactions of coordinated disintegration. Partial components of the crossbone substrate were coordinated by M-MuLV IN, indicating a reliance on both LTR and target DNA determinants for substrate assembly. The intramolecular reaction was dependent on the presence of either the HHCC domain or a crossbone LTR 5' single-stranded tail. An M-MuLV IN mutant without the HHCC domain (Ndelta105) catalyzed reduced levels of double disintegration but not single disintegration. A separately purified HHCC domain protein (Cdelta232) stimulated double disintegration mediated by Ndelta105, suggesting a role of the N-terminal HHCC domain in stable IN-IN and IN-DNA interactions. Significantly, crossbone substrates lacking the LTR 5' tails were not recognized by the fingerless Ndelta105 protein. Collectively, these data suggest similar roles of the HHCC domain and 5' LTR tail in substrate recognition and modulation of IN activity. PMID:8648728

Development of a mathematical model for physical disintegration of flushable consumer products in wastewater systems.

PubMed

Karadagli, Fatih; McAvoy, Drew C; Rittmann, Bruce E

2009-05-01

The processes that flushable solid products may undergo after discharge to wastewater systems are (1) physical disintegration of solids resulting from turbulence, (2) direct dissolution of water-soluble components, (3) hydrolysis of solids to form soluble components, and (4) biodegradation of soluble and insoluble components. We develop a mathematical model for physical disintegration of flushable solid consumer products and test it with two different flushable products--product A, which has 40% water soluble-content, and product B, which has no water-soluble components. We present our modeling analysis of experimental results, from which we computed disintegration rate constants and fractional distribution coefficients for the disintegration of larger solids. The rate constants for solids of product A in units of (hour(-1)) are 0.45 for > 8-mm, 2.25 x 10(-2) for 4- to 8-mm, 0.9 x 10(-2) for 2- to 4-mm, and 1.26 x 10(-2) for 1- to 2-mm solids. The rate constants for solids of product B in units of hour(-1) are 1.8 for > 8-mm, 1.8 for 4- to 8-mm, 3.6 x 10(-1) for 2- to 4-mm, and 2.25 x 10(-3) for 1- to 2-mm solids. As indicated by the rate constants, larger solids disintegrate at a faster rate than smaller solids. In addition, product B disintegrated much faster and went mostly to the smallest size range, while product A disintegrated more slowly and was transferred to a range of intermediate solid sizes.

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

PubMed

Epstein, S; Cryer, B; Ragi, S; Zanchetta, J R; Walliser, J; Chow, J; Johnson, M A; Leyes, A E

2003-01-01

Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Combination of alkaline and microwave pretreatment for disintegration of meat processing wastewater sludge.

PubMed

Erden, G

2013-01-01

Meat processing wastewater sludge has high organic content but it is very slow to degrade in biological processes. Anaerobic digestion may be a good alternative for this type of sludge when the hydrolysis, known to be the rate-limiting step of biological sludge anaerobic degradation, could be eliminated by disintegration. This investigation deals with disintegration of meat processing wastewater sludge. Microwave (MW) irradiation and combined alkaline pretreatment and MW irradiation were applied to sludge for disintegration purposes. Disintegration performance of the methods was evaluated with disintegration degree based on total and dissolved organic carbon calculations (DD(TOC)), and the solubilization of volatile solids (S(VS)) in the pretreated sludge. Optimum conditions were found to be 140 degrees C and 30 min for MW irradiation using response surface methodology (RSM) and pH = 13 for combined pretreatment. While DD(TOC) was observed as 24.6% and 54.9, S(VS) was determined as 8.54% and 42.5% for MW pretreated and combined pretreated sludge, respectively. The results clearly show that pre-conditioning of sludge with alkaline pretreatment played an important role in enhancing the disintegration efficiency of subsequent MW irradiation. Disintegration methods also affected the anaerobic biodegradability and dewaterability of sludge. An increase of 23.6% in biogas production in MW irradiated sludge was obtained, comparing to the raw sludge at the end of the 35 days of incubation. This increase was observed as 44.5% combined pretreatment application. While MW pretreatment led to a little improvement of the dewatering performance of sludge, in combined pretreatment NaOH deteriorates the sludge dewaterability.

Disintegration kinetics of food gels during gastric digestion and its role on gastric emptying: an in vitro analysis.

PubMed

Guo, Qing; Ye, Aiqian; Lad, Mita; Ferrua, Maria; Dalgleish, Douglas; Singh, Harjinder

2015-03-01

The understanding of the disintegration and gastric emptying of foods in the stomach is important for designing functional foods. In this study, a dynamic stomach model (human gastric simulator, HGS) was employed to investigate the disintegration and subsequent emptying of two differently structured whey protein emulsion gels (soft and hard gels).The gels were mechanically ground into fragments to reproduce the particle size distribution of an in vivo gel bolus. The simulated gel bolus was prepared by mixing gel fragments and artificial saliva, and exposed to 5 hours of simulated gastric digestion in the presence and absence of pepsin. Results showed that regardless of pepsin, the soft gel always disintegrated faster than the hard gel. The presence of pepsin significantly accelerated the disintegration of both gels. In particular, it enhanced abrasion of the soft gel into fine particles (<0.425 mm) after 180 min of processing. The emptying of the gels was influenced by the combined effects of the original particle size of the gel boluses and their disintegration kinetics in the HGS. In the presence or absence of pepsin, the larger particles of the soft gel emptied slower than the hard one during the first 120 min of process. However, in the presence of pepsin, the soft gel emptied faster than the hard one after 120 min because of a higher level of disintegration. These findings highlight the role of food structure, bolus properties and biochemical effects on the disintegration and gastric emptying patterns of gels during gastric digestion.

Strength Enhancement and Application Development of Carbon Foam for Thermal Protection Systems

DTIC Science & Technology

2004-09-01

to implementation was the inherent weakness and friability of the carbon foams. Under a MDA funded SBIR program, Ceramic Composites Inc . has...there are two approaches under consideration for utilizing carbon foams. Allcomp Inc.iii, Materials and Electrochemical Researchiv, Touchstonev...Ceramic Composites Inc . (CCI) elected to take an alternative approach to enhancing the strength of carbon foam. For our evaluation, two polymeric pre

Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

ERIC Educational Resources Information Center

Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

2013-01-01

Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case…

Minimisation of costs by using disintegration at a full-scale anaerobic digestion plant.

PubMed

Winter, A

2002-01-01

Various half-scale and lab-scale investigations have already shown that the disintegration of excess sludge is a possible pre-treatment to optimise anaerobic digestion. To control these results different methods of disintegration were investigated at a full-scale plant. Two stirred ball mills and a plant for oxidation with ozone were applied. A positive influence of disintegration on the anaerobic biodegradability can be established with application of a stirred ball mill. Biogas production as well as the degree of degradation were increased by about 20%. Laboratory investigations also validate that disintegration increases the polymer demand and leads to a lower solid content after dewatering. A higher pollution level of process water after dewatering even with ammonia and COD corroborates the results of the anaerobic degradation. Capital costs for the stirred ball mill, costs for energy, manpower and maintenance can be covered if the specific costs for disposal are high. If the development of costs in future and the current discussion about sludge disposal are taken into account sewage sludge disintegration can be a suitable technique to minimise costs at waste water treatment plants.

Lecithin, gelatin and hydrolyzed collagen orally disintegrating films: functional properties.

PubMed

Borges, J G; Silva, A G; Cervi-Bitencourt, C M; Vanin, F M; Carvalho, R A

2016-05-01

Orally disintegrating films (ODFs) can transport natural active compounds such as ethanol extract of propolis (EEP). This paper aimed to investigate the effect of lecithin on different gelatin and hydrolyzed collagen (HC) polymeric matrices with addition of EEP. ODFs were prepared by casting technique and were characterized (color parameters, water content, mechanical properties, microstructure, disintegration time (DT), infrared spectroscopy (FTIR), contact angle (CA), swelling degree and total phenolic content). The mechanical properties were influenced by HC. The microstructure demonstrated increased porosity and roughness in films with EEP, and the addition of lecithin resulted in an increase in the number of pores. Lecithin-gelatin and lecithin-EEP-gelatin interactions were observed by FTIR. The addition of HC and EEP reduced the DT and CA, and HC and lecithin reduced the swelling capacity. However, the swelling capacity was not affected by presence of EEP. The addition of lecithin to gelatin and HC ODFs may improve the incorporation and the oral transport of active compounds such as EEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of titanium dioxide mediated dairy waste activated sludge deflocculation on the efficiency of bacterial disintegration and cost of sludge management.

PubMed

Godvin Sharmila, V; Kavitha, S; Rajashankar, K; Yeom, Ick Tae; Rajesh Banu, J

2015-12-01

This investigation explores the influence of titanium dioxide (TiO2) in deflocculating (removal of extracellular polymeric substance - EPS) the sludge and subsequent biomass disintegration by bacterial pretreatment. The EPS removed at an optimized TiO2 dosage of 0.03g/g of SS of TiO2 and a solar radiation exposure time of 15min to enhance the subsequent bacterial disintegration. The outcomes of the bacterial pretreatment reveal SS reduction and COD solubilization for the deflocculated (EPS removed and bacterially pretreated) sludge was observed to be 22.8% and 22.9% which was comparatively greater than flocculated (raw sludge inoculated with bacteria) and control (raw) sludge. The higher methane production potential of about 0.43(gCOD/gVSS) was obtained in deflocculated sludge than the flocculated (0.20gCOD/gVSS) and control (0.073gCOD/gVSS). Economic assessment of this study provides a net profit of about 131.9USD/Ton in deflocculated sludge. Copyright © 2015 Elsevier Ltd. All rights reserved.

The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles.

PubMed

Torge, Afra; Grützmacher, Philipp; Mücklich, Frank; Schneider, Marc

2017-06-15

Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles. In this context we investigated the influence of mannitol on the morphology, aerodynamic properties and disintegration behavior of nano-embedded microparticles. PLGA nanoparticles and mannitol were spray dried each as sole component and in combination in three different ratios. An influence of the mannitol content on the morphology was observed. Pure mannitol microparticles were solid and spherical, while the addition of nanoparticles resulted in raisin-shaped hollow particles. The different morphologies can be explained by diffusion processes of the compounds described by the Péclet-number. All powders showed suitable aerodynamic properties. By dispersion of the powders in simulated lung fluid, initial nanoparticle sizes could be recovered for samples containing mannitol. The fraction of redispersed nanoparticles was increased with increasing mannitol content. To evaluate the disintegration under conditions with higher comparability to the in vivo situation, spray-dried powders were exposed to >90% relative humidity. The disintegration behavior was monitored by analyzing roughness values by white light interferometry and supporting SEM imaging. The exposure to high relative humidity was shown to be sufficient for disintegration of the microparticles containing mannitol, releasing morphologically unchanged nanoparticles. With increasing mannitol content, the disintegration occurred faster and to a higher degree. Under these conditions, microparticles only composed of nanoparticles did not disintegrate. By enabling the release of nanoparticles from nano-embedded microparticles, mannitol was shown to be an ideal excipient to convert nanoparticles by spray drying into an inhalable dry power formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Histotripsy Methods in Mechanical Disintegration of Tissue: Toward Clinical Applications

PubMed Central

Khokhlova, VA; Fowlkes, JB; Roberts, WW; Schade, GR; Xu, Z; Khokhlova, TD; Hall, TL; Maxwell, AD; Wang, YN; Cain, CA

2015-01-01

Purpose In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently, there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Material and Methods Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapor cavity causes tissue disintegration. Results Recent pre-clinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumors, kidney stone fragmentation, enhancing antitumor immune response, and tissue decellularization for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Conclusions Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilize different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of noninvasive surgery. PMID:25707817

ELECTRONIC ANALOG COMPUTER FOR DETERMINING RADIOACTIVE DISINTEGRATION

DOEpatents

Robinson, H.P.

1959-07-14

A computer is presented for determining growth and decay curves for elements in a radioactive disintegration series wherein one unstable element decays to form a second unstable element or isotope, which in turn forms a third element, etc. The growth and decay curves of radioactive elements are simulated by the charge and discharge curves of a resistance-capacitance network. Several such networks having readily adjustable values are connected in series with an amplifier between each successive pair. The time constant of each of the various networks is set proportional to the half-life of a corresponding element in the series represented and the charge and discharge curves of each of the networks simulates the element growth and decay curve.

Bioenhanced sublingual tablet of drug with limited permeability using novel surfactant binder and microencapsulated polysorbate: In vitro/in vivo evaluation.

PubMed

El-Setouhy, Doaa Ahmed; Basalious, Emad B; Abdelmalak, Nevine Shawky

2015-08-01

Formulation of sublingual tablets of drugs with limited permeability poses a great challenge due to their poor absorption. In this study, bioenhanced sublingual tablets (BESTs) of zolmitriptan were prepared using novel surfactant binder (Pluronic® p123/Syloid® mixture) to enhance tablet disintegration and dissolution. Microencapsulated polysorbate 80 (Sepitrap™ 80) were included in the composition of BESTs to enhance the drug transport through the sublingual mucosa. Tablets were evaluated for in vitro/in vivo disintegration, in vitro dissolution and ex vivo permeation. Solubility studies confirmed that phosphate buffer; pH 6.8 could be used as dissolution medium for sublingual tablets of zolmitriptan. BEST-5 containing Pluronic® p123/Syloid® mixture and Sepitrap™ 80 exhibited the shortest in vitro/in vivo disintegration times (<30s), the highest dissolution at early time dissolution points and the highest enhancement of drug transport through mucosal membrane. The in vivo pharmacokinetic study using human volunteers showed a significant increase in the rate and extent of sublingual absorption with less variations of Tmax after sublingual administration of both BEST-5 and Zomig-ZMT ODT. Our results proposed that Pluronic® p123/Syloid® mixture and Sepitrap™ 80 could be promising for the development of sublingual tablets for rapid onset of action of drugs with limited permeability. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of crospovidone and hydroxypropyl cellulose on carbamazepine in high-dose tablet formulation.

PubMed

Flicker, Felicia; Betz, Gabriele

2012-06-01

The aim of this study was to develop a high-dose tablet formulation of the poorly soluble carbamazepine (CBZ) with sufficient tablet hardness and immediate drug release. A further aim was to investigate the influence of various commercial CBZ raw materials on the optimized tablet formulation. Hydroxypropyl cellulose (HPC-SL) was selected as a dry binder and crospovidone (CrosPVP) as a superdisintegrant. A direct compacted tablet formulation of 70% CBZ was optimized by a 3² full factorial design with two input variables, HPC (0--10%) and CrosPVP (0--5%). Response variables included disintegration time, amount of drug released at 15 and 60 min, and tablet hardness, all analyzed according to USP 31. Increasing HPC-SL together with CrosPVP not only increased tablet hardness but also reduced disintegration time. Optimal condition was achieved in the range of 5--9% HPC and 3--5% CrosPVP, where tablet properties were at least 70 N tablet hardness, less than 1 min disintegration, and within the USP requirements for drug release. Testing the optimized formulation with four different commercial CBZ samples, their variability was still observed. Nonetheless, all formulations conformed to the USP specifications. With the excipients CrosPVP and HPC-SL an immediate release tablet formulation was successfully formulated for high-dose CBZ of various commercial sources.

Enhancement of activated sludge disintegration and dewaterability by Fenton process

NASA Astrophysics Data System (ADS)

Heng, G. C.; Isa, M. H.

2016-06-01

Municipal and industrial wastewater treatment plants produce large amounts of sludge. This excess sludge is an inevitable drawback inherent to the activated sludge process. In this study, the waste activated sludge was obtained from the campus wastewater treatment plant at Universiti Teknologi PETRONAS (UTP), Malaysia. Fenton pretreatment was optimized by using the response surface methodology (RSM) to study the effects of three operating conditions including the dosage of H2O2 (g H2O2/kg TS), the molar ratio of H2O2/Fe2+ and reaction time. The optimum operating variables to achieve MLVSS removal 65%, CST reduction 28%, sCOD 11000 mg/L and EPS 500 mg/L were: 1000 g H2O2/kg TS, H2O2/Fe2+ molar ratio 70 and reaction time 45 min. Fenton process was proved to be able to enhance the sludge disintegration and dewaterability.

Use of anaerobic hydrolysis pretreatment to enhance ultrasonic disintegration of excess sludge.

PubMed

Li, Xianjin; Zhu, Tong; Shen, Yang; Chai, Tianyu; Xie, Yuanhua; You, Meiyan; Wang, Youzhao

2016-01-01

To improve the excess sludge disintegration efficiency, reduce the sludge disintegration cost, and increase sludge biodegradability, a combined pretreatment of anaerobic hydrolysis (AH) and ultrasonic treatment (UT) was proposed for excess sludge. Results showed that AH had an advantage in dissolving flocs, modifying sludge characteristics, and reducing the difficulty of sludge disintegration, whereas UT was advantageous in damaging cell walls, releasing intracellular substances, and decomposing macromolecular material. The combined AH-UT process was an efficient method for excess sludge pretreatment. The optimized solution involved AH for 3 days, followed by UT for 10 min. After treatment, chemical oxygen demand, protein, and peptidoglycan concentrations reached 3,949.5 mg O2/L, 752.5 mg/L and 619.1 mg/L, respectively. This work has great significance for further engineering applications, namely, reducing energy consumption, increasing the sludge disintegration rate, and improving the biochemical properties of sludge.

Impact of Male Infanticide on the Social Structure of Mountain Gorillas

PubMed Central

Robbins, Andrew M.; Gray, Maryke; Basabose, Augustin; Uwingeli, Prosper; Mburanumwe, Innocent; Kagoda, Edwin; Robbins, Martha M.

2013-01-01

Infanticide can be a major influence upon the social structure of species in which females maintain long-term associations with males. Previous studies have suggested that female mountain gorillas benefit from residing in multimale groups because infanticide occurs when one-male groups disintegrate after the dominant male dies. Here we measure the impact of infanticide on the reproductive success of female mountain gorillas, and we examine whether their dispersal patterns reflect a strategy to avoid infanticide. Using more than 40 years of data from up to 70% of the entire population, we found that only 1.7% of the infants that were born in the study had died from infanticide during group disintegrations. The rarity of such infanticide mainly reflects a low mortality rate of dominant males in one-male groups, and it does not dispel previous observations that infanticide occurs during group disintegrations. After including infanticide from causes other than group disintegrations, infanticide victims represented up to 5.5% of the offspring born during the study, and they accounted for up to 21% of infant mortality. The overall rates of infanticide were 2–3 times higher in one-male groups than multimale groups, but those differences were not statistically significant. Infant mortality, the length of interbirth intervals, and the age of first reproduction were not significantly different between one-male versus multimale groups, so we found no significant fitness benefits for females to prefer multimale groups. In addition, we found limited evidence that female dispersal patterns reflect a preference for multimale groups. If the strength of selection is modest for females to avoid group disintegrations, than any preference for multimale groups may be slow to evolve. Alternatively, variability in male strength might give some one-male groups a lower infanticide risk than some multimale groups, which could explain why both types of groups remain common. PMID:24223143

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.

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.

Self-disintegrating Raney metal alloys

DOEpatents

Oden, Laurance L.; Russell, James H.

1979-01-01

A method of preparing a Raney metal alloy which is capable of self-disintegrating when contacted with water vapor. The self-disintegrating property is imparted to the alloy by incorporating into the alloy from 0.4 to 0.8 weight percent carbon. The alloy is useful in forming powder which can be converted to a Raney metal catalyst with increased surface area and catalytic activity.

Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs

PubMed Central

Castro, Silvina G.; Dib, Alicia; Suarez, Gonzalo; Allemandi, Daniel; Lanusse, Carlos; Sanchez Bruni, Sergio; Palma, Santiago D.

2013-01-01

The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form. PMID:24063016

Sludge reduction in a small wastewater treatment plant by electro-kinetic disintegration.

PubMed

Chiavola, Agostina; Ridolfi, Alessandra; D'Amato, Emilio; Bongirolami, Simona; Cima, Ennio; Sirini, Piero; Gavasci, Renato

2015-01-01

Sludge reduction in a wastewater treatment plant (WWTP) has recently become a key issue for the managing companies, due to the increasing constraints on the disposal alternatives. Therefore, all the solutions proposed with the aim of minimizing sludge production are receiving increasing attention and are tested either at laboratory or full-scale to evaluate their real effectiveness. In the present paper, electro-kinetic disintegration has been applied at full-scale in the recycle loop of the sludge drawn from the secondary settlement tank of a small WWTP for domestic sewage. After the disintegration stage, the treated sludge was returned to the biological reactor. Three different percentages (50, 75 and 100%) of the return sludge flow rate were subjected to disintegration and the effects on the sludge production and the WWTP operation efficiency evaluated. The long-term observations showed that the electro-kinetic disintegration was able to drastically reduce the amount of biological sludge produced by the plant, without affecting its treatment efficiency. The highest reduction was achieved when 100% return sludge flow rate was subjected to the disintegration process. The reduced sludge production gave rise to a considerable net cost saving for the company which manages the plant.

Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.

PubMed

Choi, Bo-Ryoung; Kim, Dong-Hee; Back, Dong Bin; Kang, Chung Hwan; Moon, Won-Jin; Han, Jung-Soo; Choi, Dong-Hee; Kwon, Kyoung Ja; Shin, Chan Young; Kim, Bo-Ram; Lee, Jongmin; Han, Seol-Heui; Kim, Hahn Young

2016-02-01

Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia. © 2015 American Heart Association, Inc.

Numerical simulation on zonal disintegration in deep surrounding rock mass.

PubMed

Chen, Xuguang; Wang, Yuan; Mei, Yu; Zhang, Xin

2014-01-01

Zonal disintegration have been discovered in many underground tunnels with the increasing of embedded depth. The formation mechanism of such phenomenon is difficult to explain under the framework of traditional rock mechanics, and the fractured shape and forming conditions are unclear. The numerical simulation was carried out to research the generating condition and forming process of zonal disintegration. Via comparing the results with the geomechanical model test, the zonal disintegration phenomenon was confirmed and its mechanism is revealed. It is found to be the result of circular fracture which develops within surrounding rock mass under the high geostress. The fractured shape of zonal disintegration was determined, and the radii of the fractured zones were found to fulfill the relationship of geometric progression. The numerical results were in accordance with the model test findings. The mechanism of the zonal disintegration was revealed by theoretical analysis based on fracture mechanics. The fractured zones are reportedly circular and concentric to the cavern. Each fracture zone ruptured at the elastic-plastic boundary of the surrounding rocks and then coalesced into the circular form. The geometric progression ratio was found to be related to the mechanical parameters and the ground stress of the surrounding rocks.

Numerical Simulation on Zonal Disintegration in Deep Surrounding Rock Mass

PubMed Central

Chen, Xuguang; Wang, Yuan; Mei, Yu; Zhang, Xin

2014-01-01

Zonal disintegration have been discovered in many underground tunnels with the increasing of embedded depth. The formation mechanism of such phenomenon is difficult to explain under the framework of traditional rock mechanics, and the fractured shape and forming conditions are unclear. The numerical simulation was carried out to research the generating condition and forming process of zonal disintegration. Via comparing the results with the geomechanical model test, the zonal disintegration phenomenon was confirmed and its mechanism is revealed. It is found to be the result of circular fracture which develops within surrounding rock mass under the high geostress. The fractured shape of zonal disintegration was determined, and the radii of the fractured zones were found to fulfill the relationship of geometric progression. The numerical results were in accordance with the model test findings. The mechanism of the zonal disintegration was revealed by theoretical analysis based on fracture mechanics. The fractured zones are reportedly circular and concentric to the cavern. Each fracture zone ruptured at the elastic-plastic boundary of the surrounding rocks and then coalesced into the circular form. The geometric progression ratio was found to be related to the mechanical parameters and the ground stress of the surrounding rocks. PMID:24592166

Investigating the response of Crane Glacier, Antarctic Peninsula to the disintegration of the Larsen B ice shelf using a 2-D flowline model

NASA Astrophysics Data System (ADS)

Campbell, A. J.; Hulbe, C. L.; Sergienko, O.

2009-12-01

Many of the glaciers flowing into the Larsen B ice shelf sped up and experienced front retreat following its March 2002 disintegration. Crane Glacier stands out among the fast responding glaciers for its dramatic increase in speed, from ~500 m/a to ~1500 m/a in its downstream reach, large surface lowering, and front retreat. Between march 2002 and early 2005, the glacier's calving front retreated by about 11.5 km to a location at which it has remained since that time. In order to investigate the physical processes that control the reaction of Crane Glacier to ice shelf disintegration, a flowline model has been developed. The model solves for the full momentum balance along the flowline using the finite element method and allows for basal sliding using a Budd type sliding relation. Model parameters are tuned to reproduce observation of surface velocity prior to ice shelf disintegration. Model can be applied diagnostically to examine instantaneous changes in boundary conditions or prognostically to evolve surface elevation over time. The instantaneous model response of the glacier to ice shelf removal produces surface velocities and thinning rates that agree well with observations. When the front position is modified to represent the steady position reached in 2005, the model again produces velocities similar to those observed on the glacier. A typical tidewater calving criterion can be used to predict the steady position toward which the front retreated. We conclude that the post-collapse speed up is facilitated by rapid basal sliding, which allows a small perturbation in vertical shearing to be amplified into a large velocity response. The pattern of glacier front retreat can be explained by a tidewater calving instability. These conclusions underscore the importance of basal sliding parametrizations in understanding observed changes in ice sheet outlet glaciers and modeling their future behavior. Correct representation of iceberg calving is also important.

Family disintegration: one fusarium verticillioides beta-lactamase at a time

USDA-ARS?s Scientific Manuscript database

Fusarium verticillioides is a mycotoxigenic fungus found commonly on maize, where it primarily exhibits asymptomatic endophytic growth. The F. verticillioides genome possesses approximately 30 regions that potentially encode beta-lactamase enzymatic domains. These enzymes are classically involved ...

Dynamical evolution and disintegration of comets

NASA Astrophysics Data System (ADS)

Kresak, L.

Current concepts of the origin and evolution of comets are reviewed. The place of their formation from which they have been delivered into the Oort reservoir is still an open problem, but the region of the outermost planets appears most probable. The interplay of stellar and planetary perturbations can be traced by model computations which reveal both the general trends and the variety of individual evolutionary paths. The present structure of the system of comets is controlled by the dynamical evolution of its individual members, limited by their physical aging by disintegration. Where the lifetimes are short, as in the Jupiter family of short-period comets, an equilibrium between elimination and replenishment is established. The role of different destructive processes and the resulting survival times are discussed.

Magnetic Resonance Imaging to Visualize Disintegration of Oral Formulations.

PubMed

Curley, Louise; Hinton, Jordan; Marjoribanks, Cameron; Mirjalili, Ali; Kennedy, Julia; Svirskis, Darren

2017-03-01

This article demonstrates that magnetic resonance imaging can visualize the disintegration of a variety of paracetamol containing oral formulations in an in vitro setting and in vivo in the human stomach. The different formulations had unique disintegration profiles which could be imaged both in vitro and in vivo. No special formulation approaches or other contrast agents were required. These data demonstrate the potential for further use of magnetic resonance imaging to investigate and understand the disintegration behavior of different formulation types in vivo, and could potentially be used as a teaching tool in pharmaceutical and medical curricula. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

PubMed Central

Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

2014-01-01

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

Instability of misoprostol tablets stored outside the blister: a potential serious concern for clinical outcome in medical abortion.

PubMed

Berard, Veronique; Fiala, Christian; Cameron, Sharon; Bombas, Teresa; Parachini, Mirella; Gemzell-Danielsson, Kristina

2014-01-01

Misoprostol (Cytotec) is recognised to be effective for many gynaecological indications including termination of pregnancy, management of miscarriage and postpartum haemorrhage. Although not licensed for such indications, it has been used for these purposes by millions of women throughout the world. Misoprostol tablets are most often packaged as multiple tablets within an aluminium strip, each within an individual alveolus. When an alveolus is opened, tablets will be exposed to atmospheric conditions. To compare the pharmaco technical characteristics (weight, friability), water content, misoprostol content and decomposition product content (type A misoprostol, type B misoprostol and 8-epi misoprostol) of misoprostol tablets Cytotec (Pfizer) exposed to air for periods of 1 hour to 720 hours (30 days), to those of identical non exposed tablets. Four hundred and twenty (420) tablets of Cytotec (Pfizer) were removed from their alveoli blister and stored at 25°C/60% relative humidity. Water content, and misoprostol degradation products were assayed in tablets exposed from 1 to 720 hours (30 days). Comparison was made with control tablets (N=60) from the same batch stored in non-damaged blisters. Statistical analyses were carried out using Fisher's exact test for small sample sizes. By 48 hours, exposed tablets demonstrated increased weight (+4.5%), friability (+1 300%), and water content (+80%) compared to controls. Exposed tablets also exhibited a decrease in Cytotec active ingredient dosage (-5.1% after 48 hours) and an increase in the inactive degradation products (+25% for type B, +50% for type A and +11% for 8-epi misoprostol after 48 hours) compared to controls. Exposure of Cytotec tablets to 'typical' European levels of air and humidity results in significant time-dependent changes in physical and biological composition that could impact adversely upon clinical efficacy. Health professionals should be made aware of the degradation of misoprostol with inappropriate storage of misoprostol tablets.

Instability of Misoprostol Tablets Stored Outside the Blister: A Potential Serious Concern for Clinical Outcome in Medical Abortion

PubMed Central

Berard, Veronique; Fiala, Christian; Cameron, Sharon; Bombas, Teresa; Parachini, Mirella; Gemzell-Danielsson, Kristina

2014-01-01

Introduction Misoprostol (Cytotec) is recognised to be effective for many gynaecological indications including termination of pregnancy, management of miscarriage and postpartum haemorrhage. Although not licensed for such indications, it has been used for these purposes by millions of women throughout the world. Misoprostol tablets are most often packaged as multiple tablets within an aluminium strip, each within an individual alveolus. When an alveolus is opened, tablets will be exposed to atmospheric conditions. Objective To compare the pharmaco technical characteristics (weight, friability), water content, misoprostol content and decomposition product content (type A misoprostol, type B misoprostol and 8-epi misoprostol) of misoprostol tablets Cytotec (Pfizer) exposed to air for periods of 1 hour to 720 hours (30 days), to those of identical non exposed tablets. Methods Four hundred and twenty (420) tablets of Cytotec (Pfizer) were removed from their alveoli blister and stored at 25°C/60% relative humidity. Water content, and misoprostol degradation products were assayed in tablets exposed from 1 to 720 hours (30 days). Comparison was made with control tablets (N = 60) from the same batch stored in non-damaged blisters. Statistical analyses were carried out using Fisher’s exact test for small sample sizes. Results By 48 hours, exposed tablets demonstrated increased weight (+4.5%), friability (+1 300%), and water content (+80%) compared to controls. Exposed tablets also exhibited a decrease in Cytotec active ingredient dosage (−5.1% after 48 hours) and an increase in the inactive degradation products (+25% for type B, +50% for type A and +11% for 8-epi misoprostol after 48 hours) compared to controls. Conclusion Exposure of Cytotec tablets to ‘typical’ European levels of air and humidity results in significant time-dependent changes in physical and biological composition that could impact adversely upon clinical efficacy. Health professionals should be made aware of the degradation of misoprostol with inappropriate storage of misoprostol tablets. PMID:25502819

Numerical simulation of phenomenon on zonal disintegration in deep underground mining in case of unsupported roadway

NASA Astrophysics Data System (ADS)

Han, Fengshan; Wu, Xinli; Li, Xia; Zhu, Dekang

2018-02-01

Zonal disintegration phenomenon was found in deep mining roadway surrounding rock. It seriously affects the safety of mining and underground engineering and it may lead to the occurrence of natural disasters. in deep mining roadway surrounding rock, tectonic stress in deep mining roadway rock mass, horizontal stress is much greater than the vertical stress, When the direction of maximum principal stress is parallel to the axis of the roadway in deep mining, this is the main reasons for Zonal disintegration phenomenon. Using ABAQUS software to numerical simulation of the three-dimensional model of roadway rupture formation process systematically, and the study shows that when The Direction of maximum main stress in deep underground mining is along the roadway axial direction, Zonal disintegration phenomenon in deep underground mining is successfully reproduced by our numerical simulation..numerical simulation shows that using ABAQUA simulation can reproduce Zonal disintegration phenomenon and the formation process of damage of surrounding rock can be reproduced. which have important engineering practical significance.

Impact of the excess sludge modification with selected chemical reagents on the increase of dissolved organic substances concentration compounds transformations in activated sludge.

PubMed

Zawieja, Iwona; Lidia, Wolny; Marta, Próba

2017-07-01

Submission of excess sludge initial disintegration process significantly affects the efficiency of anaerobic stabilization process. Expression of increasing the concentration of organic matter in dissolved form is to increase sludge disintegration. As a result of chemical modification is an increase of the chemical oxygen demand and the concentration of volatile fatty acids. The aim of this study was to determine the impact of the disintegration process with selected chemical reagents to increase the concentration of organic substances in dissolved form. The process of chemical disintegration of excess sludge was treated using the following reagents: Mg(OH) 2 , Ca(OH) 2 , HCl, H 2 SO 4 , H 2 O 2 . The modification was carried out at ambient temperature for 2, 6 and 24h. During sludge disintegration it was noticed the growth of indicators values that confirmed the susceptibility of prepared sludge to biodegradation. Copyright © 2017 Elsevier Inc. All rights reserved.

Fenton mediated ultrasonic disintegration of sludge biomass: Biodegradability studies, energetic assessment, and its economic viability.

PubMed

Kavitha, S; Rajesh Banu, J; IvinShaju, C D; Kaliappan, S; Yeom, Ick Tae

2016-12-01

Mechanical disintegration of sludge through ultrasonication demands high energy and cost. Therefore, in the present study, a comprehensive investigation was performed to analyze the potential of a novel method, fenton mediated sonic disintegration (FSD). In FSD process, extracellular polymeric substance (EPS) of sludge was first removed via fenton treatment. It was subsequently disintegrated via ultrasonication. Energetic assessment and economic analysis were then performed using net energy and cost gain (spent) as key factor to evaluate the practical viability of the FSD process. FSD was found to be superior over sonic disintegration based on its higher sludge solubilization (34.4% vs. 23.2%) and methane production potential (0.3gCOD/gCOD vs. 0.2gCOD/gCOD). Both energy analysis and cost assessment of the present study revealed that FSD could reduce the energy demand of ultrasonication considerably with a positive net profit of about 44.93USD/Ton of sludge. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics

PubMed Central

Lei, Ting; Guan, Ming; Liu, Jia; Lin, Hung-Cheng; Pfattner, Raphael; McGuire, Allister F.; Huang, Tsung-Ching; Shao, Leilai; Cheng, Kwang-Ting; Tok, Jeffrey B.-H.; Bao, Zhenan

2017-01-01

Increasing performance demands and shorter use lifetimes of consumer electronics have resulted in the rapid growth of electronic waste. Currently, consumer electronics are typically made with nondecomposable, nonbiocompatible, and sometimes even toxic materials, leading to serious ecological challenges worldwide. Here, we report an example of totally disintegrable and biocompatible semiconducting polymers for thin-film transistors. The polymer consists of reversible imine bonds and building blocks that can be easily decomposed under mild acidic conditions. In addition, an ultrathin (800-nm) biodegradable cellulose substrate with high chemical and thermal stability is developed. Coupled with iron electrodes, we have successfully fabricated fully disintegrable and biocompatible polymer transistors. Furthermore, disintegrable and biocompatible pseudo-complementary metal–oxide–semiconductor (CMOS) flexible circuits are demonstrated. These flexible circuits are ultrathin (<1 μm) and ultralightweight (∼2 g/m2) with low operating voltage (4 V), yielding potential applications of these disintegrable semiconducting polymers in low-cost, biocompatible, and ultralightweight transient electronics. PMID:28461459

Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics.

PubMed

Lei, Ting; Guan, Ming; Liu, Jia; Lin, Hung-Cheng; Pfattner, Raphael; Shaw, Leo; McGuire, Allister F; Huang, Tsung-Ching; Shao, Leilai; Cheng, Kwang-Ting; Tok, Jeffrey B-H; Bao, Zhenan

2017-05-16

Increasing performance demands and shorter use lifetimes of consumer electronics have resulted in the rapid growth of electronic waste. Currently, consumer electronics are typically made with nondecomposable, nonbiocompatible, and sometimes even toxic materials, leading to serious ecological challenges worldwide. Here, we report an example of totally disintegrable and biocompatible semiconducting polymers for thin-film transistors. The polymer consists of reversible imine bonds and building blocks that can be easily decomposed under mild acidic conditions. In addition, an ultrathin (800-nm) biodegradable cellulose substrate with high chemical and thermal stability is developed. Coupled with iron electrodes, we have successfully fabricated fully disintegrable and biocompatible polymer transistors. Furthermore, disintegrable and biocompatible pseudo-complementary metal-oxide-semiconductor (CMOS) flexible circuits are demonstrated. These flexible circuits are ultrathin (<1 μm) and ultralightweight (∼2 g/m 2 ) with low operating voltage (4 V), yielding potential applications of these disintegrable semiconducting polymers in low-cost, biocompatible, and ultralightweight transient electronics.

FDA-Approved Natural Polymers for Fast Dissolving Tablets

PubMed Central

Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

2014-01-01

Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

External scintigraphy in monitoring the behavior of pharmaceutical formulations in vivo I: technique for acquiring high-resolution images of tablets

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

Theodorakis, M.C.; Simpson, D.R.; Leung, D.M.

1983-02-01

A new method for monitoring tablet disintegration in vivo was developed. In this method, the tablets were labeled with a short-lived radionuclide, technetium 99m, and monitored by a gamma camera. Several innovations were introduced with this method. First, computer reconstruction algorithms were used to enhance the scintigraphic images of the disintegrating tablet in vivo. Second, the use of a four-pinhole collimator to acquire multiple views of the tablet resulted in high count rates and reduced acquisition times of the scintigraphic images. Third, the magnification of the scintigraphic images achieved by pinhole collimation led to significant improvement in resolution. Fourth, themore » radioinuclide was incorporated into the granulation so that the whole mass of the tablet was uniformly labeled with high levels of activity. This technique allowed the continuous monitoring of the disintegration process of tablets in vivo in experimental animals. Multiple pinhole collimation and the labeling process permitted the acquisition of quality scintigraphic images of the labeled tablet every 30 sec. The resolution of the method was tested in vitro and in vivo.« less

Fate of return activated sludge after ozonation: an optimization study for sludge disintegration.

PubMed

Demir, Ozlem; Filibeli, Ayse

2012-09-01

The effects of ozonation on sludge disintegration should be investigated before the application of ozone during biological treatment, in order to minimize excess sludge production. In this study, changes in sludge and supernatant after ozonation of return activated sludge were investigated for seven different ozone doses. The optimum ozone dose to avoid inhibition of ozonation and high ozone cost was determined in terms of disintegration degree as 0.05 g O3/gTS. Suspended solid and volatile suspended solid concentrations of sludge decreased by 77.8% and 71.6%, respectively, at the optimum ozone dose. Ozonation significantly decomposed sludge flocs. The release of cell contents was proved by the increase of supernatant total nitrogen (TN) and phosphorus (TP). While TN increased from 7 mg/L to 151 mg/L, TP increased from 8.8 to 33 mg/L at the optimum ozone dose. The dewaterability and filterability characteristics of the ozonated sludge were also examined. Capillary suction time increased with increasing ozone dosage, but specific resistance to filtration increased to a specific value and then decreased dramatically. The particle size distribution changed significantly as a result of floc disruption at an optimum dose of 0.05 gO3/gTS.

The potential for sea-level-rise-induced barrier island loss: Insights from the Chandeleur Islands, Louisiana, USA

USGS Publications Warehouse

Moore, Laura J.; Patsch, Kiki; List, Jeffrey H.; Williams, S. Jeffress

2014-01-01

As sea level rises and hurricanes become more intense, barrier islands around the world become increasingly vulnerable to conversion from self-sustaining migrating landforms to submerging or subaqueous sand bodies. To explore the mechanism by which such state changes occur and to assess the factors leading to island disintegration, we develop a suite of numerical simulations for the Chandeleur Islands in Louisiana, U.S.A., which appear to be on the verge of this transition. Our results suggest that the Chandeleurs are likely poised to change state, leading to their demise, within decades depending on future storm history. Contributing factors include high rates of relative sea level rise, limited sediment supply, muddy substrate, current island position relative to former Mississippi River distributary channels, and the effects of changes in island morphology on sediment transport pathways. Although deltaic barrier islands are most sensitive to disintegration because of their muddy substrate, the importance of relative sea level rise rate in determining the timing of threshold crossing suggests that the conceptual models for deltaic barrier island formation and disintegration may apply more broadly in the future.

The extreme mobility of debris avalanches: A new model of transport mechanism

NASA Astrophysics Data System (ADS)

Perinotto, Hélène; Schneider, Jean-Luc; Bachèlery, Patrick; Le Bourdonnec, François-Xavier; Famin, Vincent; Michon, Laurent

2015-12-01

Large rockslide-debris avalanches, resulting from flank collapses that shape volcanoes and mountains on Earth and other object of the solar system, are rapid and dangerous gravity-driven granular flows that travel abnormal distances. During the last 50 years, numerous physical models have been put forward to explain their extreme mobility. The principal models are based on fluidization, lubrication, or dynamic disintegration. However, these processes remain poorly constrained. To identify precisely the transport mechanisms during debris avalanches, we examined morphometric (fractal dimension and circularity), grain size, and exoscopic characteristics of the various types of particles (clasts and matrix) from volcanic debris avalanche deposits of La Réunion Island (Indian Ocean). From these data we demonstrate for the first time that syn-transport dynamic disintegration continuously operates with the increasing runout distance from the source down to a grinding limit of 500 µm. Below this limit, the particle size reduction exclusively results from their attrition by frictional interactions. Consequently, the exceptional mobility of debris avalanches may be explained by the combined effect of elastic energy release during the dynamic disintegration of the larger clasts and frictional reduction within the matrix due to interactions between the finer particles.

Orally disintegrating dosage forms and taste-masking technologies; 2010.

PubMed

Douroumis, Dennis

2011-05-01

In the last decade the development of orally disintegrating tablets (ODTs) and thin-film platforms has grown enormously in the field of pharmaceutical industry. A wide variety of new masking technologies combined with the aforementioned platforms have been developed in order to mask the taste of bitter active substances and achieve patient compliance. The commercial success and viability of such products requires the development of robust formulations with excellent palatability, disintegration times, physicochemical stability and pharmacokinetic profiles. In this review, emerging taste-masking technologies applied to solid dosage form manufacturing are summarized. The unique features and principles of taste-masking approaches used with ODT platforms are discussed, including the advantages and limitations of each technology. A brief discussion is also included on the taste masking of thin-film technologies, owing to their similar applications and requirements. This review elucidates the unique features of current commercially available or highly promising ODT and thin-film technologies, along with taste-masking approaches used in the manufacturing of oral solid dosage forms. A better understanding of these drug delivery approaches will help researchers to select the appropriate platform, or to develop innovative products with improved safety, compliance and clinical value.

Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories.

PubMed

Saleem, M A; Taher, M; Sanaullah, S; Najmuddin, M; Ali, Javed; Humaira, S; Roshan, S

2008-09-01

Rectal suppositories of tramadol hydrochloride were prepared using different bases and polymers like PEG, cocoa butter, agar and the effect of different additives on in vitro release of tramadol hydrochloride was studied. The agar-based suppositories were non-disintegrating/non-dissolving, whereas PEGs were disintegrating/dissolving and cocoa butter were melting suppositories. All the prepared suppositories were evaluated for various physical parameters like weight variation, drug content and hardness. The PEG and cocoa butter suppositories were evaluated for macromelting range, disintegration and liquefaction time. In vitro release study was performed by USP type I apparatus. The prepared suppositories were within the permissible range of all physical parameters. In vitro drug release was in the order of PEG>Agar>cocoa butter. Addition of PVP, HPMC in agar suppositories retards the release. The mechanism of drug release was diffusion controlled and follows first order kinetics. The results suggested that blends of PEG of low molecular weight (1000) with high molecular weight (4000 and 6000) in different percentage and agar in 10% w/w as base used to formulate rapid release suppositories. The sustained release suppositories can be prepared by addition of PVP, HPMC in agar-based suppositories and by use of cocoa butter as base.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

PubMed

Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ohike, Atsuo; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro

2005-11-28

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound. Sustained-release profiles of NiD from DCMT were identically controlled in several dissolution mediums in spite of varying pH and agitation speed. The release of NiD from DCMT was sustained more effectively by increasing the amount of wax or by decreasing the amount of disintegrant, and supersaturation of NiD was achieved without any re-crystallization in dissolution medium. The release rate of NiD from DCMT was controlled by the disintegration rate of tablet. The release profile of NiD was described by the Hixson-Crowell's model better than zero-order kinetics, first-order kinetics and Higuchi's model, which supports that the release of NiD from DCMT is regulated by the disintegration of the tablet. From this study, it was clarified that DCMT was one of the promising SR systems applying SD for the poorly water-soluble drugs.

Disintegration of nano-embedded microparticles after deposition on mucus: A mechanistic study.

PubMed

Ruge, Christian A; Bohr, Adam; Beck-Broichsitter, Moritz; Nicolas, Valérie; Tsapis, Nicolas; Fattal, Elias

2016-03-01

The conversion of colloidal drug carriers/polymeric nanoparticles into dry microparticulate powders (e.g., by spray-drying) is a prominent approach to overcome the aerodynamic limitations of these formulations for delivery via inhalation. However, to what extent such nano-embedded microparticles disintegrate into individual/intact nanoparticles after contacting relevant physiological media has so far not been addressed. Polymeric nanoparticles were spray-dried into nano-embedded microparticles (NEMs) using different amounts of trehalose as embedding matrix excipient. Formulations were characterized and then evaluated for their disintegration behavior after aerosolization onto model mucus. Although a rapid and complete aqueous redispersion was observed for specific excipient/nanoparticle weight ratios (i.e., greater than 1/1), the same formulations revealed no disintegration after deposition onto a static mucus layer. Double-labeled NEMs powders (i.e., dual color staining of polymeric nanoparticles and trehalose) demonstrated rapid matrix dissolution, while the nanoparticle aggregates persisted. When deposited onto agitated mucus, however, sufficient disintegration of NEMs into individual polymeric nanoparticles was observed. These findings indicate that mechanical forces are necessary to overcome the attraction between individual nanoparticles found within the NEMs. Thus, it remains questionable whether the lung mechanics (e.g., breathing, mucociliary clearance) acting on these formulations will contribute to the overall disintegration process. Copyright © 2015 Elsevier B.V. All rights reserved.

Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films.

PubMed

Mazumder, Sonal; Pavurala, Naresh; Manda, Prashanth; Xu, Xiaoming; Cruz, Celia N; Krishnaiah, Yellela S R

2017-07-15

The present investigation was carried out to understand the impact of formulation and process variables on the quality of oral disintegrating films (ODF) using Quality by Design (QbD) approach. Lamotrigine (LMT) was used as a model drug. Formulation variable was plasticizer to film former ratio and process variables were drying temperature, air flow rate in the drying chamber, drying time and wet coat thickness of the film. A Definitive Screening Design of Experiments (DoE) was used to identify and classify the critical formulation and process variables impacting critical quality attributes (CQA). A total of 14 laboratory-scale DoE formulations were prepared and evaluated for mechanical properties (%elongation at break, yield stress, Young's modulus, folding endurance) and other CQA (dry thickness, disintegration time, dissolution rate, moisture content, moisture uptake, drug assay and drug content uniformity). The main factors affecting mechanical properties were plasticizer to film former ratio and drying temperature. Dissolution rate was found to be sensitive to air flow rate during drying and plasticizer to film former ratio. Data were analyzed for elucidating interactions between different variables, rank ordering the critical materials attributes (CMA) and critical process parameters (CPP), and for providing a predictive model for the process. Results suggested that plasticizer to film former ratio and process controls on drying are critical to manufacture LMT ODF with the desired CQA. Published by Elsevier B.V.

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.

The Rate of Decay of Fission Products

DOE PAGES

May, K.; Wigner, Eugene P.

1948-06-01

By considering the fission products as a sort of statistical assembly, calculations have been made of the β -disintegrations per second and of the total energy emitted per second at any time after fission has taken place (cf. Fig. 6). The results are in good agreement with experiment. The theoretical work is based on the assumption that the mass of a nucleus of mass number A and charge Z is given by a ( Z 0 ( A ) - Z ) 2 + b . Empirical values for a and b are used. Use is also made of anmore » approximate empirical relationship between half-life and disintegration energy. A further basic hypothesis which is important for the results at very short times after fission has taken place is that, in the most probable way of splitting, the chain lengths of the light and heavy fragments are equal and that there is not much deviation from this most probable mode of fission. (See L. E. Glendenin, C. D. Coryell, R. R. Edwards, and M. H. Feldman, CL-LEG-1. A tentative explanation has been given recently by R. D. Present, Phys. Rev. 72, 7 (1947).) The average number of β -disintegrations per fission is found to be 6; the average energy of all radiations ( β, γ, and neutrino) of the fission products is 21.5 ± 3 Mev. Apparently, about half of this energy escapes in the form of neutrinos and a quarter is emitted in the form of β and in the form of γ rays.« less

A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance.

PubMed

Al-Khattawi, Ali; Koner, Jasdip; Rue, Peter; Kirby, Dan; Perrie, Yvonne; Rajabi-Siahboomi, Ali; Mohammed, Afzal R

2015-08-01

The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 151MPa and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods. Tablet porosity increased from 0.20±0.002 for pure mannitol to 0.53±0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135±5.29s for pure mannitol to 75.33±2.52-31.67±1.53s for mannitol 110-170°C. Hardness increased by 150% at 110°C (258.67±28.89N) and 30% at 150°C (152.70±10.58N) compared to pure mannitol tablets (104.17±1.70N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying. Copyright © 2015 Elsevier B.V. All rights reserved.

Psychosocial predictors of cannabis use in adolescents at risk.

PubMed

Hüsler, Gebhard; Plancherel, Bernard; Werlen, Egon

2005-09-01

This research has tested a social disintegration model in conjunction with risk and protection factors that have the power to differentiate relative, weighted interactions among variables in different socially disintegrated groups. The model was tested in a cross-sectional sample of 1082 at-risk youth in Switzerland. Structural equation analyses show significant differences between the social disintegration (low, moderate, high) groups and gender, indicating that the model works differently for groups and for gender. For the highly disintegrated adolescents results clearly show that the risk factors (negative mood, peer network, delinquency) are more important than the protective factors (family relations, secure sense of self). Family relations lose all protective value against negative peer influence, but personal variables, such as secure self, gain protective power.

Comments on filament-disintegration and its relation to other aspects of solar activity.

NASA Technical Reports Server (NTRS)

Dodson, H. W.; Hedeman, E. R.; Rovira De Miceli, M.

1972-01-01

Studies of sudden disintegrations of filaments in solar cycles 19 and 20 (to 1969) indicate that such events occur frequently. Approximately 30% of all large filaments in these cycles disintegrated in the course of their transit across the solar disk. 'Major' flares occurred with above average frequency on the last day on which 141 large disappearing filaments were observed. Relationships between a disintegrating filament on July 10-11, 1959, a prior major flare, a newly formed spot, and concomitant growth of H-alpha plage are presented. Observation of prior descending prominence material apparently directed towards the location of the flare of July 15, 1959 is reported. The development of the filament-associated flare of Feb. 13, 1967 is described.

A pharmaceutical study on lornoxicam fast disintegrating tablets: formulation and in vitro and in vivo evaluation.

PubMed

Moutasim, Mohamed Yousif; ElMeshad, Aliaa Nabil; El-Nabarawi, Mohamed Ahmed

2017-06-01

Lornoxicam is an anti-inflammatory drug used to relieve rheumatoid arthritis pain, but the low water solubility and bitter taste of the drug present challenges for formulation as fast disintegrating tablets (FDTs). Complexation of the drug with β-cyclodextrin was initially carried out to increase the drug solubility and to mask its bitter taste. Tablets were prepared by direct compression of drug complex (DC), F-Melt, mannitol, crospovidone, and sodium starch glycolate (SSG). FDTs were characterized in terms of disintegration time (DT) and dissolution. A bioequivalence study was carried out using (Zeficam® tablets (Eva Pharma) as reference with the help of human volunteers (n = 4). The chosen formula (F2, DC 24 mg, F-Melt 88.4 mg, and crospovidone 5 mg) exhibited the shortest in vitro (18 s) and in vivo DT (13 s), and the percent drug released after Q6min was 95.90%. Following administration of F2 and Zeficam®, the respective maximum drug plasma concentrations (C max ) were 510 and 532.5 ng/mL, at times (T max ) of 1 and 2.5 h, of mean residence times (MRTs) of 12.25 and 11.35 h and of areas under the plasma curve [AUC(0-24)] of 5080.253 and 4815.775 ng/h/mL. There were significant differences in T max and MRT of both treatments (p < 0.05). Moreover, the volunteers found F2 to be palatable. FDTs could be considered as promising dosage forms for lornoxicam as they exhibited a short in vivo DT and an increased rate of drug release and attained a relative bioavailability of 105.49%. This could offer a fast relief of pain accompanying rheumatoid arthritis.

Simultaneous Gram and viability staining on activated sludge exposed to erythromycin: 3D CLSM time-lapse imaging of bacterial disintegration.

PubMed

Louvet, Jean-Noël; Attik, Ghania; Dumas, Dominique; Potier, Olivier; Pons, Marie-Noëlle

2011-11-01

The effect of erythromycin on activated sludge bacteria according to their Gram type was investigated with 3-dimensional Confocal Laser Scanning Microscopy (CLSM) time-lapse imaging. The fluorescent stains SYTOX Green and Texas Red-X conjugate of wheat germ agglutinin stained dying bacteria and Gram(+) bacteria respectively. Time-lapse imaging allowed an understanding of the staining mechanism and the measurement of the death rate. In presence of erythromycin (10mg/L), Gram(+) bacteria had a higher mortality rate than the Gram(-) bacteria. This result suggests that antibiotic in wastewater could change the activated sludge bacteria composition, according to their Gram type by selecting the bacteria which are the least sensitive to the antibiotics. However bacterial death was followed by bacterial disintegration leading to a decrease in the fluorescence. Results suggested that the viability indicators based on membrane integrity should be used with a correct sampling method, which can give the initial quantity of living bacteria. Copyright © 2011 Elsevier GmbH. All rights reserved.

Evolution of arched roofs in salt caves: Role of gravity-induced stress and relative air humidity and temperature changes (Zagros Mts., Iran)

NASA Astrophysics Data System (ADS)

Bruthans, Jiri; Filippi, Michal; Zare, Mohammad

2016-04-01

In salt caves in the halite karst in SE Iran the disintegration of rock salt into individual grains can be observed. Highly disintegrated blocks and individual grains form a major volume of debris in many caves on islands in the Persian Gulf. Larger cave rooms have often perfectly arched roof. The perfect geometry of rooms and interlocking of salt grains indicate that evolution of room cross-sections in these caves is controlled by feedback between gravity-induced stress and rock salt disintegration in similar way as in evolution of sandstone landforms (Bruthans et al. 2014). Those portions of rock salt, which are under compressional stress, disintegrate much slower than portions under tensile stress. Important question is the kind of weathering mechanism responsible for intergranular disintegration of rock salt. The relationship between disintegration, its rate and cave climate was studied. Clearly the fastest disintegration rate was found in caves with strong air circulation (i.e, short caves with large cross-sections, open on both ends). Temperature and air humidity changes are considerable in these caves. On the other hand the disintegration is very slow in the inner parts of long caves with slow air circulation or caves with one entrance. The best example of such caves is the inner part of 3N Cave on Namakdan salt diapir with nearly no air circulation and stable temperature and humidity, where disintegration of rock salt into grains is missing. Strong effect of cave climate on disintegration rate can be explained by deliquescence properties of halite. Halite is absorbing air moisture forming NaCl solution if relative humidity (RH) exceeds 75 % (at 20-30 oC). In the Persian Gulf region the RH of the air is passing the 75 % threshold in case of 91% days (Qeshm Island, years 2002-2005), while in mountainous areas in mainland this threshold is less commonly reached. In most of nights (91 %) in Persian Gulf the air with RH >75 % is entering the salt caves and air moisture is wetting the dry rock and slightly diluting the percolating brine in ceiling of the caves, which is otherwise just saturated with respect to halite. During days the RH is <75% and brine partly dries up and precipitates halite. By repeating the cycle of dissolution and precipitation of halite and possibly also by temperature changes the rock salt is disintegrated into interlocked salt grains, whose behavior is then strongly controlled by gravity-induced stress. Research was funded by the Czech Science Foundation (GA CR No. 16-19459S). Reference: Bruthans J, Soukup J., Vaculíková J., Filippi M., Schweigstillova J., Mayo A.L., Masin D., Kletetschka G.,Rihosek J. (2014): Sandstone landforms shaped by negative feedback between stress and erosion. Nature Geoscience 7(8): 597-601.

Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

PubMed

Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

2010-06-01

The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

Disintegration of collagen fibrils by Glucono-δ-lactone: An implied lead for disintegration of fibrosis.

PubMed

Jayamani, Jayaraman; Ravikanth Reddy, R; Madhan, Balaraman; Shanmugam, Ganesh

2018-02-01

Excess accumulation of collagen (fibrosis) undergoes self-aggregation, which leads to fibrillar collagen, on the extracellular matrix is the hallmark of a number of diseases such as keloids, hypertrophic scars, and systemic scleroderma. Direct inhibition or disintegration of collagen fibrils by small molecules offer a therapeutic approach to prevent or treat the diseases related to fibrosis. Herein, the anti-fibrotic property of Glucono-δ-lactone (GdL), known as acidifier, on the fibrillation and its disintegration of collagen was investigated. As collagen fibrillation is pH dependent, the pH modulation property of GdL is attractive to inhibit self-association of collagen. Optical density and microscopic data indicate that GdL elicits concentration-dependent fibril inhibition and also disintegrates pre-formed collagen fibrils. The simultaneous pH analysis showed that the modulation(lowering) of pH by GdL is the primary cause for its anti-fibrotic activity. The intact triple helical structure of collagen upon treatment of GdL suggests that collagen fibril disintegration can be achieved without affecting the native structure of collagen which is essential for any anti-fibrotic agents. Saturation transfer difference (STD) NMR result reveals that GdL is in proximity to collagen. The present results thus suggest that GdL provides a lead to design novel anti-fibrotic agents for the pathologies related to collagen deposition. Copyright © 2017 Elsevier B.V. All rights reserved.

Palatal Seam Disintegration: To Die or Not to Die? That Is No Longer the Question

PubMed Central

Nawshad, Ali

2008-01-01

Formation of the medial epithelial seam (MES) by palatal shelf fusion is a crucial step of palate development. Complete disintegration of the MES is the final essential phase of palatal confluency with surrounding mesenchymal cells. In general, the mechanisms of palatal seam disintegration are not overwhelmingly complex, but given the large number of interacting constituents; their complicated circuitry involving feedforward, feedback, and crosstalk; and the fact that the kinetics of interaction matter, this otherwise simple mechanism can be quite difficult to interpret. As a result of this complexity, apparently simple but highly important questions remain unanswered. One such question pertains to the fate of the palatal seam. Such questions may be answered by detailed and extensive quantitative experimentation of basic biological studies (cellular, structural) and the newest molecular biological determinants (genetic/dye cell lineage, gene activity, kinase/enzyme activity), as well as animal model (knockouts, transgenic) approaches. System biology and cellular kinetics play a crucial role in cellular MES function; omissions of such critical contributors may lead to inaccurate understanding of the fate of MES. Excellent progress has been made relevant to elucidation of the mechanism(s) of palatal seam disintegration. Current understanding of palatal seam disintegration suggests epithelial–mesenchymal transition and/or programmed cell death as two most common mechanisms of MES disintegration. In this review, I discuss those two mechanisms and the differences between them. PMID:18629865

Accelerating the sludge disintegration potential of a novel bacterial strain Planococcus jake 01 by CaCl2 induced deflocculation.

PubMed

Kavitha, S; Saranya, T; Kaliappan, S; Adish Kumar, S; Yeom, Ick Tae; Rajesh Banu, J

2015-01-01

The present study investigates the impacts of phase separated disintegration through CaCl2 (calcium chloride) mediated biosurfactant producing bacterial pretreatment. In the initial phase of the study, the flocs were disintegrated (deflocculation) with 0.06g/gSS of CaCl2. In the subsequent phase, the sludge biomass was disintegrated (cell disintegration) through potent biosurfactant producing new novel bacteria, Planococcus jake 01. The pretreatment showed that suspended solids reduction and chemical oxygen demand solubilization for deflocculated - bacterially pretreated sludge was found to be 17.14% and 14.14% which were comparatively higher than flocculated sludge (treated with bacteria alone). The biogas yield potential of deflocculated - bacterially pretreated, flocculated, and control sludges were observed to be 0.322(L/gVS), 0.225(L/gVS) and 0.145(L/gVS) respectively. To our knowledge, this is the first study to present the thorough knowledge of biogas production potential through a novel phase separated biosurfactant bacterial pretreatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of a novel electric field-assisted modified hydrodynamic cavitation system for disintegration of waste activated sludge.

PubMed

Jung, Kyung-Won; Hwang, Min-Jin; Yun, Yeo-Myeong; Cha, Min-Jung; Ahn, Kyu-Hong

2014-09-01

In this current study, we present a modified hydrodynamic cavitation device that combines an electric field to substitute for the chemical addition. A modified HC system is basically an orifice plate and crisscross pipe assembly, in which the crisscross pipe imparts some turbulence, which creates collision events. This study shows that for maximizing disintegration, combining HC system, which called electric field-assisted modified orifice plate hydrodynamic cavitation (EFM-HC) in this study, with an electric field is important. Various HC systems were compared in terms of disintegration of WAS, and, among them, the EFM-HC system exhibited the best performance with the highest disintegration efficiency of 47.0±2.0% as well as the destruction of WAS morphological characteristics. The experimental results clearly show that a conventional HC system was successfully modified. In addition, electric field has a great potential for efficient disintegration of WAS for as a additional option in a combination treatment. This study suggests continued research in this field may lead to an appropriate design for commercial use. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhancement of aerobic biodegradability potential of municipal waste activated sludge by ultrasonic aided bacterial disintegration.

PubMed

Kavitha, S; Jessin Brindha, G M; Sally Gloriana, A; Rajashankar, K; Yeom, Ick Tae; Rajesh Banu, J

2016-01-01

An investigation was performed to study the influence of ultrasonic aided bacterial disintegration on the aerobic degradability of sludge. In first phase of the study, effective floc disruption was achieved at an ultrasonic specific energy input of 2.45kJ/kg TS with 44.5mg/L of Extracellular Polymeric Substance (EPS) release including 0.035U/mL and 0.025U/mL protease and amylase activity respectively. In second phase, experimental outcomes revealed bacterial disintegration of floc disrupted-sludge showing a maximum solubilization of about 23% and was observed to be superior to bacterially disintegrated (11%) and control (6%), respectively. The result of aerobic biodegradability of ultrasonic aided bacterially pretreated sludge showed volatile solids (VS) degradation of about 40.2%. The kinetic study of aerobic biodegradability through non linear regression modelling reveals that floc disrupted sludge showed better biodegradability with decay constant of about 0.19d(-1) relatively higher than the control (0.14d(-1)) and bacterially disintegrated (0.17d(-1)) sludges. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sewage sludge disintegration by combined treatment of alkaline+high pressure homogenization.

PubMed

Zhang, Yuxuan; Zhang, Panyue; Zhang, Guangming; Ma, Weifang; Wu, Hao; Ma, Boqiang

2012-11-01

Alkaline pretreatment combined with high pressure homogenization (HPH) was applied to promote sewage sludge disintegration. For sewage sludge with a total solid content of 1.82%, sludge disintegration degree (DD(COD)) with combined treatment was higher than the sum of DD(COD) with single alkaline and single HPH treatment. NaOH dosage ⩽0.04mol/L, homogenization pressure ⩽60MPa and a single homogenization cycle were the suitable conditions for combined sludge treatment. The combined sludge treatment showed a maximum DD(COD) of 59.26%. By regression analysis, the combined sludge disintegration model was established as 11-DD(COD)=0.713C(0.334)P(0.234)N(0.119), showing that the effect of operating parameters on sludge disintegration followed the order: NaOH dosage>homogenization pressure>number of homogenization cycle. The energy efficiency with combined sludge treatment significantly increased compared with that with single HPH treatment, and the high energy efficiency was achieved at low homogenization pressure with a single homogenization cycle. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dissolution Rate, Weathering Mechanics, and Friability of TNT, Comp B, Tritonal, and Octol

DTIC Science & Technology

2010-02-01

second conceptual model also simulates dissolution of a particle that experiences constant soil moisture such as one mixed in with the soil...or are mediated by moisture on the particle surface is not yet known. The identities of these red products are also unknown as are their health...it using the outdoor data. The model assumes that raindrops intercepted by HE particles were fully saturated in HE as they dripped off. Particle

The use of Hibiscus esculentus (Okra) gum in sustaining the release of propranolol hydrochloride in a solid oral dosage form.

PubMed

Zaharuddin, Nurul Dhania; Noordin, Mohamed Ibrahim; Kadivar, Ali

2014-01-01

The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength.

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.

Multiple-layer compression-coated tablets: formulation and humidity studies of novel chewable amoxicillin/clavulanate tablet formulations.

PubMed

Wardrop, J; Jaber, A B; Ayres, J W

1998-08-01

The purpose of this study was to produce novel multiple-layer, compression-coated, chewable tablet formulations containing amoxicillin trihydrate, and clavulanic acid as potassium clavulanate, and to test in vitro dissolution characteristics and the effect of humidity stability compared to Augmentin chewable tablets as a reference. Double- and triple-layer tablets were manufactured on a laboratory scale by multiple-layer dry compression, and dissolution profiles of both active ingredients were determined. Tablets were subjected to stability evaluation in laboratory-scale humidity tanks maintained at constant humidity. Assay of content was determined by HPLC or UV spectroscopy. Physical characteristics of the powder mixture, such as angle of repose, and of tablets for hardness and friability, were also determined. Chewable tablets showed similar dissolution profiles in vitro for both active ingredients, compared to the marketed reference, Augmentin. The stability of clavulanic acid, but not amoxicillin, was increased in the novel triple or bilayer formulation. The tablets showed suitable friability, hardness, and angle of repose for starting materials to suggest that industrial scale-up is feasible. This approach to formulation of drugs containing multiple or moisture-sensitive ingredients has been shown to increase the stability of the central core drug without changing the dissolution pattern of the active ingredients. This formulation is expected to be bioequivalent in vivo based on these in vitro results.

The Use of Hibiscus esculentus (Okra) Gum in Sustaining the Release of Propranolol Hydrochloride in a Solid Oral Dosage Form

PubMed Central

Noordin, Mohamed Ibrahim; Kadivar, Ali

2014-01-01

The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength. PMID:24678512

Components of released liquid from ultrasonic waste activated sludge disintegration.

PubMed

Wang, Fen; Lu, Shan; Ji, Min

2006-05-01

Ultrasound can be applied as a pretreatment to disintegrate sludge. In this paper, by observing the solution concentration of polysaccharide, protein, DNA, Ca and Mg before and after disintegration, the main components in the released liquid are analyzed. It has been found that the predominant component of the released liquid in this research is protein. Ultrasound can destroy the extracellular polymeric substances (EPS), which is important to the sludge flocs structure. Ca2+ and Mg2+, which play a key role in binding the EPS are released into the aqueous phase. As a result, the sludge flocs are loosened. Under the effect of the hydraulic shear force, the sludge is disintegrated. Then the hydraulic shear forces destroy the cell walls, the substances inside the cells are released into the aqueous phase.

Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2016-02-01

To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

PubMed

Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

2011-07-01

Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin bioavailability in the fed state is largely (and probably entirely) due to gastric degradation to DCA. Capsules can provide a useful and elegant dosage form for almost all drugs, but may result in a negative food effect for drugs as acid-labile as azithromycin.

A comparative study on seismic response of two unstable rock slopes within same tectonic setting but different activity level

NASA Astrophysics Data System (ADS)

Kleinbrod, Ulrike; Burjánek, Jan; Hugentobler, Marc; Amann, Florian; Fäh, Donat

2017-12-01

In this study, the seismic response of two slope instabilities is investigated with seismic ambient vibration analysis. Two similar sites have been chosen: an active deep-seated slope instability at Cuolm da Vi and the geologically, structurally and morphologically similar, but presently not moving Alp Caschlè slope. Both slopes are located at the upper Vorderrheintal (Canton Graubünden, Switzerland). Ambient vibrations were recorded on both slopes and processed by time-frequency polarization and site-to-reference spectral ratio analysis. The data interpretation shows correlations between degree of disintegration of the rock mass and amplification. However, the ambient vibration analysis conducted, does not allow retrieving a resonance frequency that can be related to the total depth of the instability of Cuolm da Vi. Even though seismic waves can be hardly traced in rock instabilities containing open fractures, it was possible to retrieve a dispersion curve and a velocity profile from the array measurement at Cuolm da Vi due to the high level of disintegration of the rock material down to a depth of about 100 m. From the similar amplification pattern at the two sites, we expect a similar structure, indicating that also the slope at Alp Caschlè was active in the past in a similar manner as Cuolm da Vi. However, a smoother increase of amplification with frequency is observed at Alp Caschlè, which might indicate less disintegration of the rock mass in a particular depth range at this site, when comparing to Cuolm da Vi where a high level of disintegration is observed, resulting from the high activity at the slope. From the frequency-dependent amplification, we can distinguish between two parts within both instabilities, one part showing decreasing disintegration of the rock mass with increasing depth, for the other parts less-fractured blocks are observed. Since the block structures are found in the lower part of the instabilities, they might contribute to the stability of the slopes. Using the velocity profiles, it was possible to estimate the depth of the two largest open fractures (i.e. tension cracks) at Cuolm da Vi.

Influence of mechanical disintegration on the microbial growth of aerobic sludge biomass: A comparative study of ultrasonic and shear gap homogenizers by oxygen uptake measurements.

PubMed

Divyalakshmi, P; Murugan, D; Sivarajan, M; Saravanan, P; Lajapathi Rai, C

2015-11-01

Wastewater treatment plant incorporates physical, chemical and biological processes to treat and remove the contaminants. The main drawback of conventional activated sludge process is the huge production of excess sludge, which is an unavoidable byproduct. The treatment and disposal of excess sludge costs about 60% of the total operating cost. The ideal way to reduce excess sludge production during wastewater treatment is by preventing biomass formation within the aerobic treatment train rather than post treatment of the generated sludge. In the present investigation two different mechanical devices namely, Ultrasonic and Shear Gap homogenizers have been employed to disintegrate the aerobic biomass. This study is intended to restrict the multiplication of microbial biomass and at the same time degrade the organics present in wastewater by increasing the oxidative capacity of microorganisms. The disintegrability on biomass was determined by biochemical methods. Degree of inactivation provides the information on inability of microorganisms to consume oxygen upon disruption. The soluble COD quantifies the extent of release of intra cellular compounds. The participation of disintegrated microorganism in wastewater treatment process was carried out in two identical respirometeric reactors. The results show that Ultrasonic homogenizer is very effective in the disruption of microorganisms leading to a maximum microbial growth reduction of 27%. On the other hand, Shear gap homogenizer does not favor the sludge growth reduction rather it facilitates the growth. This study also shows that for better microbial growth reduction, floc size reduction alone is not sufficient but also microbial disruption is essential. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of hydrodynamic disintegration to accelerate anaerobic digestion of surplus activated sludge.

PubMed

Grübel, Klaudiusz; Machnicka, Alicja

2009-12-01

Hydrodynamic disintegration of activated sludge resulted in organic matter and polymers transfer from the solid phase into the liquid phase. Disintegration by hydrodynamic cavitation had a positive effect on the degree and rate of excess sludge anaerobic digestion. Also, addition of a part of anaerobic digested sludge containing adapted microorganisms resulted in acceleration of the process. The disruption of cells of foam microorganisms and addition to the digestion process led to an increase of biogas production.

Anesthetic management with scalp nerve block and propofol/remifentanil infusion during awake craniotomy in an adolescent patient -A case report-

PubMed Central

Sung, Bohyun; Park, Jin-Woo; Byon, Hyo-Jin; Kim, Jin-Tae; Kim, Chong Sung

2010-01-01

Despite of various neurophysiologic monitoring methods under general anesthesia, functional mapping at awake state during brain surgery is helpful for conservation of speech and motor function. But, awake craniotomy in children or adolescents is worrisome considering their emotional friabilities. We present our experience on anesthetic management for awake craniotomy in an adolescent patient. The patient was 16 years old male who would undergo awake craniotomy for removal of brain tumor. Scalp nerve block was done with local anesthetics and we infused propofol and remifentanil with target controlled infusion. The patient endured well and was cooperative before scalp suture, but when surgeon sutured scalp, he complained of pain and was suddenly agitated. We decided change to general anesthesia. Neurosurgeon did full neurologic examinations and there was no neurologic deficit except facial palsy of right side. Facial palsy had improved with time. PMID:21286435

Nuclear Stability Rules

NASA Astrophysics Data System (ADS)

Feather, N.

2016-03-01

General preface; Author's preface; 1. The systematics of stable nuclei; 2. Regularities in x-disintegration; 3. Regularities in β-disintegration; 4. Spontaneous fission and the number of the elements; References and author index; Subject index.

[From the history of Radom's gynaecology].

PubMed

Wiraszka, Robert

2002-03-01

The aim of the work is to present a study of the gynaecology in Radom until 1947. The base of this study are prints, memoires and anniversary studies, both published and in typescript. Considering the scantiness of sources, disintegrated archives and time passed, the study is popularizing in character.

A novel coating concept for ileo-colonic drug targeting: proof of concept in humans using scintigraphy.

PubMed

Varum, F J O; Hatton, G B; Freire, A C; Basit, A W

2013-08-01

The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans. Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT S neutralised to pH 8.0 and a buffer salt (10% KH₂PO₄), which was overcoated with layer of standard EUDRAGIT S organic solution. For comparison, a single coating system was produced by applying the same amount of EUDRAGIT S organic solution on the tablet cores. Dissolution tests on the tablets were carried out using USP II apparatus in 0.1N HCl for 2 h and subsequently in pH 7.4 Krebs bicarbonate buffer. For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations. Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study. The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded. There was no drug release from the single-coated or double-coated tablets in 0.1N HCl for 2h. The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120 min, while in contrast drug release from the double-coated tablets was initiated at 60 min. In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained. The in vivo disintegration of the single-coated EUDRAGIT S tablets in the large intestine was erratic. Furthermore, in 2 volunteers, the single-coated tablet was voided intact. Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum. The accelerated in vivo disintegration of the double-coating EUDRAGIT S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets. Moreover, Krebs bicarbonate buffer has the ability to discriminate between formulations designed to target the ileo-colonic region. Copyright © 2013 Elsevier B.V. All rights reserved.

Ondansetron

MedlinePlus

... by your doctor.If you are taking the rapidly disintegrating tablet, remove the tablet from the package just before ... of reach of children. Store the tablets and rapidly disintegrating tablets away from light, at room temperature or in ...

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets.

PubMed

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH's intrinsic characteristics.

Youth and violence: Phenomena and international data.

PubMed

Legge, Sandra

2008-01-01

The topic of youth, violence, and disintegration needs addressing because young women and men are the world's greatest capital. They have the energy, talent, and creativity for building a future. But this group also suffers grave vulnerabilities. The time of adolescence includes important and difficult periods of life (for example, becoming more independent from the family, finding an adequate position in society, and starting a family of one's own). All of these points are strongly correlated with social integration, employment, and a place in the labor market--important factors in this context.This article gives an overview of the international development and the actual situation of socially harmful behavior among youths--both fatal violence (homicide) and nonfatal violence (such as bullying, fighting, and carrying weapons). The author shows that different kinds of youth violence represent social problems in every society. The data show that youths are not only perpetrators but also the group with the highest risk of becoming victims of violence. Furthermore, the data from around the world show that their vulnerability is not limited to this sphere. It arises also from their social conditions, especially their high risk of being disintegrated from the labor market. The parallels in the data underline the significance of a functioning institutional structure without positing a deterministic relationship between the risk of economic disintegration and violent behavior.

Mathematical modelling of liquid transport in swelling pharmaceutical immediate release tablets.

PubMed

Markl, Daniel; Yassin, Samy; Wilson, D Ian; Goodwin, Daniel J; Anderson, Andrew; Zeitler, J Axel

2017-06-30

Oral dosage forms are an integral part of modern health care and account for the majority of drug delivery systems. Traditionally the analysis of the dissolution behaviour of a dosage form is used as the key parameter to assess the performance of a drug product. However, understanding the mechanisms of disintegration is of critical importance to improve the quality of drug delivery systems. The disintegration performance is primarily impacted by the hydration and subsequent swelling of the powder compact. Here we compare liquid ingress and swelling data obtained using terahertz pulsed imaging (TPI) to a set of mathematical models. The interlink between hydration kinetics and swelling is described by a model based on Darcy's law and a modified swelling model based on that of Schott. Our new model includes the evolution of porosity, pore size and permeability as a function of hydration time. Results obtained from two sets of samples prepared from pure micro-crystalline cellulose (MCC) indicate a clear difference in hydration and swelling for samples of different porosities and particle sizes, which are captured by the model. Coupling a novel imaging technique, such as TPI, and mathematical models allows better understanding of hydration and swelling and eventually tablet disintegration. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

PubMed Central

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

The increasing role of monoamine oxidase type B inhibitors in Parkinson's disease therapy.

PubMed

Elmer, Lawrence W; Bertoni, John M

2008-11-01

The role of monoamine oxidase type B inhibitors in the treatment of Parkinson's disease has expanded with the new monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets. As primary therapy in early disease monoamine oxidase B inhibitors reduce motor disability and delay the need for levodopa. In more advanced disease requiring levodopa, adjunctive monoamine oxidase B inhibitors reduce 'off' time and may improve gait and freezing. Rasagiline and selegiline oral disintegrating tablets may reduce the safety risks associated with the amfetamine and methamfetamine metabolites of conventional oral selegiline while retaining or improving therapeutic efficacy. Articles were identified by searches of PubMed and searches on the Internet and reviewed. All articles and other referenced materials were retrieved using the keywords 'Parkinson's disease', 'treatment' and 'monoamine oxidase B inhibitor' and were published between 1960 and 2007, with older references selected for historical significance. Only papers published in English were reviewed. Accumulating data support the use of monoamine oxidase B inhibitors as monotherapy for early and mild Parkinson's disease and as adjunctive therapy for more advanced Parkinson's disease with levodopa-associated motor fluctuations. The recently released monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets, have potential advantages over conventional oral selegiline.

Positive Disintegration as a Process of Symmetry Breaking.

PubMed

Laycraft, Krystyna

2017-04-01

This article presents an analysis of the positive disintegration as a process of symmetry breaking. Symmetry breaking plays a major role in self-organized patterns formation and correlates directly to increasing complexity and function specialization. According to Dabrowski, a creator of the Theory of Positive Disintegration, the change from lower to higher levels of human development requires a major restructuring of an individual's psychological makeup. Each level of human development is a relatively stable and coherent configuration of emotional-cognitive patterns called developmental dynamisms. Their main function is to restructure a mental structure by breaking the symmetry of a low level and bringing differentiation and then integration to higher levels. The positive disintegration is then the process of transitions from a lower level of high symmetry and low complexity to higher levels of low symmetry and high complexity of mental structure.

Impact of influent COD/N ratio on disintegration of aerobic granular sludge.

PubMed

Luo, Jinghai; Hao, Tianwei; Wei, Li; Mackey, Hamish R; Lin, Ziqiao; Chen, Guang-Hao

2014-10-01

Disintegration of aerobic granular sludge (AGS) is a challenging issue in the long-term operation of an AGS system. Chemical oxygen demand (COD)-to-nitrogen (N) ratio (COD/N), often variable in industrial wastewaters, could be a destabilizing factor causing granule disintegration. This study investigates the impact of this ratio on AGS disintegration and identifies the key causes, through close monitoring of AGS changes in its physical and chemical characteristics, microbial community and treatment performance. For specific comparison, two lab-scale air-lift type sequencing batch reactors, one for aerobic granular and the other for flocculent sludge, were operated in parallel with three COD/N ratios (4, 2, 1) applied in the influent of each reactor. The decreased COD/N ratios of 2 and 1 strongly influenced the stability of AGS with regard to physical properties and nitrification efficiency, leading to AGS disintegration when the ratio was decreased to 1. Comparatively the flocculent sludge maintained relatively stable structure and nitrification efficiency under all tested COD/N ratios. The lowest COD/N ratio resulted in a large microbial community shift and extracellular polymeric substances (EPS) reduction in both flocculent and granular sludges. The disintegration of AGS was associated with two possible causes: 1) reduction in net tyrosine production in the EPS and 2) a major microbial community shift including reduction in filamentous bacteria leading to the collapse of granule structure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Youth and Violence: Phenomena and International Data

ERIC Educational Resources Information Center

Legge, Sandra

2008-01-01

The topic of youth, violence, and disintegration needs addressing because young women and men are the world's greatest capital. They have the energy, talent, and creativity for building a future. But this group also suffers grave vulnerabilities. The time of adolescence includes important and difficult periods of life (for example, becoming more…

Foreign Assistance Dependency: Breaking the Cycle Through Advanced Education

DTIC Science & Technology

2010-12-01

authorized the U.S. government to confiscate church assets due to its practice of polygamy . At this time, the fund was disintegrated with around $435,000...legal issues with the federal government over polygamy and uncertainty about how to handle new members.262 Although United Order communities were

The Social Psychology of Disintegrative Shaming in Education

ERIC Educational Resources Information Center

Brown, Joel H.; Clarey, Amy M.

2012-01-01

Despite considerable research concerning drug education and zero tolerance policies, few have examined their combined youth impact. Comprehensive and nationally recognized mixed method evidence is drawn from 77 school districts and 118 schools in the Drug, Alcohol and Tobacco Education (DATE) evaluation. For the first time it is found that the…

Chemokine Signaling during Midline Epithelial Seam Disintegration Facilitates Palatal Fusion

PubMed Central

Suttorp, Christiaan M.; Cremers, Niels A.; van Rheden, René; Regan, Raymond F.; Helmich, Pia; van Kempen, Sven; Kuijpers-Jagtman, Anne M.; Wagener, Frank A.D.T.G.

2017-01-01

Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO), which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO) mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling. PMID:29164113

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.

Possible Disintegrating Planet Artist Concept

NASA Image and Video Library

2012-05-21

This artist concept depicts a comet-like tail of a possible disintegrating super Mercury-size planet candidate as it transits, or crosses, its parent star, named KIC 12557548. The results are based on data from NASA Kepler mission.

Constraining properties of disintegrating exoplanets

NASA Astrophysics Data System (ADS)

Veras, D.; Carter, P. J.; Leinhardt, Z. M.; Gänsicke, B. T.

2017-09-01

Evaporating and disintegrating planets provide unique insights into chemical makeup and physical constraints. The striking variability, depth (˜10 - 60%) and shape of the photometric transit curves due to the disintegrating minor planet orbiting white dwarf WD 1145+017 has galvanised the post-main- sequence exoplanetary science community. We have performed the first tidal disruption simulations of this planetary object, and have succeeded in constraining its mass, density, eccentricity and physical nature. We illustrate how our simulations can bound these properties, and be used in the future for other exoplanetary systems.

Effect of moisture on disintegration kinetics during anaerobic digestion of complex organic substrates.

PubMed

Liotta, Flavia; d'Antonio, Giuseppe; Esposito, Giovanni; Fabbricino, Massimiliano; Frunzo, Luigi; van Hullebusch, Eric D; Lens, Piet N L; Pirozzi, Francesco

2014-01-01

The role of the moisture content and particle size (PS) on the disintegration of complex organic matter during the wet anaerobic digestion (AD) process was investigated. A range of total solids (TS) from 5% to 11.3% and PS from 0.25 to 15 mm was evaluated using carrot waste as model complex organic matter. The experimental results showed that the methane production rate decreased with higher TS and PS. A modified version of the AD model no.1 for complex organic substrates was used to model the experimental data. The simulations showed a decrease of the disintegration rate constants with increasing TS and PS. The results of the biomethanation tests were used to calibrate and validate the applied model. In particular, the values of the disintegration constant for various TS and PS were determined. The simulations showed good agreement between the numerical and observed data.

Influence of diligent disintegration on anaerobic biomass and performance of microbial fuel cell.

PubMed

Divyalakshmi, Palanisamy; Murugan, Devaraj; Rai, Chockalingam Lajapathi

2017-12-01

To enhance the performance of microbial fuel cells (MFC) by increasing the surface area of cathode and diligent mechanical disintegration of anaerobic biomass. Tannery effluent and anaerobic biomass were used. The increase in surface area of the cathode resulted in 78% COD removal, with the potential, current density, power density and coulombic efficiency of 675 mV, 147 mA m -2 , 33 mW m -2 and 3.5%, respectively. The work coupled with increased surface area of the cathode with diligent mechanical disintegration of the biomass, led to a further increase in COD removal of 82% with the potential, current density, power density and coulombic efficiency of 748 mV, 229 mA m -2 , 78 mW m -2 and 6% respectively. Mechanical disintegration of the biomass along with increased surface area of cathode enhances power generation in vertical MFC reactors using tannery effluent as fuel.

Nystatin and lidocaine pastilles for the local treatment of oral mucositis.

PubMed

Silva, Filipa Cosme; Marto, Joana M; Salgado, Ana; Machado, Paula; Silva, Alexandra N; Almeida, António J

2017-03-01

Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy in oncology. Its treatment requires oral formulations that enhance therapy compliance, improve administration and ensure drug effectiveness. Solid dosage forms that act by slow dissolution, such as pastilles, are an effective alternative to mouthwashes, for their versatility, ease of administration and extended residence time in the oral cavity. The present work describes the development and stability studies of an innovative formulation of nystatin and lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical quality testing was carried out, including disintegration and dissolution testing, texture profile analysis, grittiness and an antifungal activity testing. A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was obtained, presenting suitable pharmaceutical characteristics, as a disintegration time of 17 ± 2 min, dissolution rate and microbiological and physicochemical for 30 days when stored at 2-8 °C under light protection. Palatability was also evaluated, being well accepted by a panel of 38 healthy volunteers. This formulation allows an accurate drug dosing by the prescriber, while enabling the patients to control the retention time of the drugs in the oral cavity and consequently manage their pain treatment.

The Impact of Disintegrant Type, Surfactant, and API Properties on the Processability and Performance of Roller Compacted Formulations of Acetaminophen and Aspirin.

PubMed

Zhao, Junshu; Koo, Otilia; Pan, Duohai; Wu, Yongmei; Morkhade, Dinesh; Rana, Sandeep; Saha, Partha; Marin, Arturo

2017-09-01

In formulation development, certain excipients, even though used in small quantities, can have a significant impact on the processability and performance of the dosage form. In this study, three common disintegrants, croscarmellose sodium (CCS), crospovidone (xPVP), and sodium starch glycolate (SSG) as well as the surfactant sodium lauryl sulfate (SLS) were evaluated for their impact on the processability and performance of a typical dry granulation formulation. Two model compounds, the mechanically brittle and chemically inert acetaminophen and the mechanically ductile carboxylic acid aspirin, were used for the evaluation. It was found that the disintegrants were generally identical in their impact on the processability and little difference was observed in the granulation and compression processes. The exception is that when xPVP was used in the formulation of the brittle acetaminophen, lower compression forces were needed to reach the same tablet hardness, suggesting a binding effect of xPVP for such systems. In general, CCS and xPVP tend to provide slightly better disintegration than SSG. However, in the case of aspirin, a strong hydrogen bonding interaction between the carboxylic acid group of aspirin and the carbonyl group of xPVP was observed, resulting in slower release of the drug after fast disintegration. SLS was found to have a significant impact on the processability due to its lubricating effect, resulting in higher compression forces needed to achieve the target tablet hardness. Due to the higher degree of compression, the disintegration and dissolution of both drugs became slower despite the wetting effect of SLS.

Extrusion-spheronization: process variables and characterization.

PubMed

Sinha, V R; Agrawal, M K; Agarwal, A; Singh, G; Ghai, D

2009-01-01

Multiparticulate systems have undergone great development in the past decade fueled by the better understanding of their multiple roles as a suitable delivery system. With the passage of time, significant advances have been made in the process of pelletization due to the incorporation of specialized techniques for their development. Extrusion-spheronization seems to be the most promising process for the optimum delivery of many potent drugs having high systemic toxicity. It also offers immense pharmaceutical applicability due to the benefits of high loading capacity of active ingredient(s), narrow size distribution, and cost-effectiveness. On application of a specific coat, these systems can also aid in site-specific delivery, thereby enhancing the bioavailability of many drugs. The current review focuses on the process of extrusion-spheronization and the operational (extruder types, screen pressure, screw speed, temperature, moisture content, spheronization load, speed and time) and formulation (excipients and drugs) variables, which may affect the quality of the final pellets. Various methods for the evaluation of the quality of the pellets with regard to the size distribution, shape, friability, granule strength, density, porosity, flow properties, and surface texture are discussed.

Microforms in gravel bed rivers: Formation, disintegration, and effects on bedload transport

USGS Publications Warehouse

Strom, K.; Papanicolaou, A.N.; Evangelopoulos, N.; Odeh, M.

2004-01-01

This research aims to advance current knowledge on cluster formation and evolution by tackling some of the aspects associated with cluster microtopography and the effects of clusters on bedload transport. The specific objectives of the study are (1) to identify the bed shear stress range in which clusters form and disintegrate, (2) to quantitatively describe the spacing characteristics and orientation of clusters with respect to flow characteristics, (3) to quantify the effects clusters have on the mean bedload rate, and (4) to assess the effects of clusters on the pulsating nature of bedload. In order to meet the objectives of this study, two main experimental scenarios, namely, Test Series A and B (20 experiments overall) are considered in a laboratory flume under well-controlled conditions. Series A tests are performed to address objectives (1) and (2) while Series B is designed to meet objectives (3) and (4). Results show that cluster microforms develop in uniform sediment at 1.25 to 2 times the Shields parameter of an individual particle and start disintegrating at about 2.25 times the Shields parameter. It is found that during an unsteady flow event, effects of clusters on bedload transport rate can be classified in three different phases: a sink phase where clusters absorb incoming sediment, a neutral phase where clusters do not affect bedload, and a source phase where clusters release particles. Clusters also increase the magnitude of the fluctuations in bedload transport rate, showing that clusters amplify the unsteady nature of bedload transport. A fourth-order autoregressive, autoregressive integrated moving average model is employed to describe the time series of bedload and provide a predictive formula for predicting bedload at different periods. Finally, a change-point analysis enhanced with a binary segmentation procedure is performed to identify the abrupt changes in the bedload statistic characteristics due to the effects of clusters and detect the different phases in bedload time series using probability theory. The analysis verifies the experimental findings that three phases are detected in the bedload rate time series structure, namely, sink, neutral, and source. ?? ASCE / JUNE 2004.

Disintegration in Peru - Consolidation in Chile: The Case for Militant Capitalism in Latin America

DTIC Science & Technology

1990-06-01

organization Comision Chilena de Derechos Humanos (CCDH), (which along with the Church-sponsored Vicaria de la Solaridad are the principal watchdog...34 reported by Chile’s human rights group Comision de Desechos Humanos (CCDH), the majority reflect a particular 134 period in time during which DINA was the

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.

Confinement by carbon nanotubes drastically alters the boiling and critical behavior of water droplets.

PubMed

Chaban, Vitaly V; Prezhdo, Victor V; Prezhdo, Oleg V

2012-03-27

Vapor pressure grows rapidly above the boiling temperature, and past the critical point liquid droplets disintegrate. Our atomistic simulations show that this sequence of events is reversed inside carbon nanotubes (CNT). Droplets disintegrate first and at low temperature, while pressure remains low. The droplet disintegration temperature is independent of the CNT diameter. In contrast, depending on CNT diameter, a temperature that is much higher than the bulk boiling temperature is required to raise the internal pressure. The control over pressure by CNT size can be useful for therapeutic drug delivery. © 2012 American Chemical Society

[Oral disintegrating tablets. A new, modern, solid dosage form].

PubMed

Popa, Graţiela; Gafiţanu, Eliza

2003-01-01

The pharmaceutical market shows lately an increasing interest in orally disintegrating tablets, due to their good acceptability among certain age categories (ex. elderly, children), and other patients with difficulties in swallowing classic solid dosage forms. Some of the methods of preparing such tablets have gained industrial applicability: molding, lyophilization, direct compression with highly soluble excipients, super disintegrants and/or effervescent systems. Some of the patients have had a good impact on the pharmaceutical market and more improvements are expected in the next few years, with new drugs to be formulated as fast dissolving dosage formulations.

Drug abuse: consequences in terms of family pathology and disintegration.

PubMed

Visser, L

1991-01-01

This article examines some of the consequences of drug addiction in terms of family pathology and family disintegration. It briefly elucidates the role of the family in developing and maintaining drug addiction in family members. The concept of 'secondary' sufferers of the illness of drug addiction is examined. An actual case history will be presented in order to facilitate analysis of some of the forms of pathology and disintegration so often seen in the family of the drug addict. Within the family context, the question of who, if anyone, is the victim of drug addiction, is raised.

How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant.

PubMed

Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

2017-01-01

This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Holding fast.

PubMed

Gourville, John T

2005-06-01

CEO Peter Walsh faces a classic innovator's dilemma. His company, Crescordia, produces high-quality metal plates, pins, and screws that orthopedic surgeons use to repair broken bones. In fact, because the company has for decades refused to compromise on quality, there are orthopedic surgeons who use nothing but Crescordia hardware. And now these customers have begun to clamor for the next generation technology: resorbable hardware. Resorbables offer clear advantages over the traditional hardware. Like dissolving sutures, resorbable plates and screws are made of biodegradable polymers. They hold up long enough to support a healing bone, then gradually and harmlessly disintegrate in the patient's body. Surgeons are especially looking forward to using resorbables on children, so kids won't have to undergo a second operation to remove the old hardware after their bones heal, a common procedure in pediatrics. The new products, however, are not yet reliable; they fail about 8% of the time, sometimes disintegrating before the bone completely heals and sometimes not ever fully disintegrating. That's why Crescordia, mindful of its hard-earned reputation, has delayed launching a line using the new technology. But time is running out. A few competitors have begun to sell resorbables despite their imperfections, and these companies are picking up market share. Should Crescordia join the fray and risk tarnishing its brand? Or should the company sit tight until it can offer a perfect product? Commenting on this fictional case study are Robert A. Lutz, vice chairman of product development at General Motors; Clayton M. Christensen, the Robert and Jane Cizik Professor of Business Administration at Harvard Business School; Jason Wittes, a senior equity analyst covering medical supplies and devices at Leerink Swann; and Nick Galakatos, a general partner of MPM Capital.

Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion.

PubMed

Guggi, Davide; Marschütz, Michaela K; Bernkop-Schnürch, Andreas

2004-04-15

This study examined the influence of the pH on the mucoadhesive and cohesive properties of polyarcylic acid (PAA) and thiolated PAA. The pH of PAA (molecular mass: 450 kDa) and of a corresponding PAA-cysteine conjugate was adjusted to 3, 4, 5, 6, 7 and 8. The amount of immobilised thiol groups and disulfide bonds was determined via Ellman's reagent. Tablets were compressed out of each pH-batch of both thiolated and unmodified PAA and the swelling behaviour, the disintegration time and the mucoadhesiveness were evaluated. The amount of thiol/disulfide groups per gram thiolated PAA of pH 3 and pH 8 was determined to be 332 +/- 94 micromol and 162 +/- 46 micromol, respectively. The thiolated PAA tablets displayed a minimum four-fold higher water uptake compared to unmodified PAA tablets. A faster and higher water uptake of both polymer types was observed above pH 5. Thiolated polymer tablets showed a 3-20-fold more prolonged disintegration time than unmodified PAA tablets. The cohesiveness of PAA-cysteine conjugate increased at higher pH, whereas the unmodified PAA behaved inversely. A 3-7-fold stronger mucoadhesiveness was observed for the PAA-cysteine conjugate tablets compared to unmodified PAA tablets. For both thiolated and unmodified polymer the mucoadhesiveness was 2-4-fold enhanced below pH 5. The difference in mucoadhesion between the two polymer types was most pronounced at these lower pH values. In this study substantial information regarding the pH-dependence of mucoadhesion and cohesion of unmodified polyacrylates and of thiolated polyacrylates is provided, representing helpful basic information for an ameliorated deployment of these polymers.

Orodispersible films and tablets with prednisolone microparticles.

PubMed

Brniak, Witold; Maślak, Ewelina; Jachowicz, Renata

2015-07-30

Orodispersible tablets (ODTs) and orodispersible films (ODFs) are solid oral dosage forms disintegrating or dissolving rapidly when placed in the mouth. One of the main issues related to their preparation is an efficient taste masking of a bitter drug substance. Therefore, the aim of this study was to prepare and evaluate the microparticles intended to mask a bitter taste of the prednisolone and use them in further preparation of two orodispersible dosage forms. Microparticles based on the Eudragit E PO or E 100 as a taste-masking agent were prepared with spray-drying technique. Tablets containing microparticles, co-processed ODT excipient Pharmaburst, and lubricant were directly compressed with single-punch tablet press. Orodispersible films were prepared by casting polymeric solutions of hydroxypropyl methylcellulose containing uniformly dispersed microparticles. Physicochemical properties of microparticles were evaluated, as well as mechanical properties analysis, disintegration time measurements and dissolution tests were performed for prepared dosage forms. Both formulations showed good mechanical resistance while maintaining excellent disintegration properties. The dissolution studies showed good masking properties of microparticles with Eudragit E 100. The amount of prednisolone released during the first minute in phosphate buffer 6.8 was around 0.1%. After incorporation into the orodispersible forms, the amount of released prednisolone increased significantly. It was probably the effect of faster microparticles wetting in orodispersible forms and their partial destruction by compression force during tableting process. Copyright © 2015 Elsevier B.V. All rights reserved.

Mathematical modelling of disintegration-limited co-digestion of OFMSW and sewage sludge.

PubMed

Esposito, G; Frunzo, L; Panico, A; d'Antonio, G

2008-01-01

This paper presents a mathematical model able to simulate under dynamic conditions the physical, chemical and biological processes prevailing in a OFMSW and sewage sludge anaerobic digestion system. The model proposed is based on differential mass balance equations for substrates, products and bacterial groups involved in the co-digestion process and includes the biochemical reactions of the substrate conversion and the kinetics of microbial growth and decay. The main peculiarity of the model is the surface based kinetic description of the OFMSW disintegration process, whereas the pH determination is based on a nine-order polynomial equation derived by acid-base equilibria. The model can be applied to simulate the co-digestion process for several purposes, such as the evaluation of the optimal process conditions in terms of OFMSW/sewage sludge ratio, temperature, OFMSW particle size, solid mixture retention time, reactor stirring rate, etc. Biogas production and composition can also be evaluated to estimate the potential energy production under different process conditions. In particular, model simulations reported in this paper show the model capability to predict the OFMSW amount which can be treated in the digester of an existing MWWTP and to assess the OFMSW particle size diminution pre-treatment required to increase the rate of the disintegration process, which otherwise can highly limit the co-digestion system. Copyright IWA Publishing 2008.

Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas.

PubMed

Ito, Yoshitaka; Maeda, Atsushi; Kondo, Hiromu; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2016-09-10

The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus. Copyright © 2016 Elsevier B.V. All rights reserved.

Local shock-wave lithotripsy of distal ureteral calculi.

PubMed

Voges, G E; Wilbert, D M; Stöckle, M; Hohenfellner, R

1988-01-01

Since the initiation of the clinical trial utilizing a second-generation lithotripor (Lithostar, Siemens, Erlangen, FRG), 96 patients with distal ureteral calculi (i.e. calculi below the pelvic brim) underwent local shock-wave lithotripsy. Routine treatment was conducted under intravenous sedation and light analgesia only. Complete stone disintegration was achieved in 84 patients (87.5%), 11 requiring two sessions and 1 patient, three. In 7 patients ureteroscopy became necessary after unsuccessful local shock-wave treatment. In 2 of these patients a 9-french flexible ureteroscope and the Storz Q-switched neodymium-YAG laser was used for stone disintegration. In 3 cases loop extraction and in 2 cases open surgery had to be performed for definitive stone removal. All pre- and postoperative manipulations (except open surgery) were done on the Lithostar. Local shock-wave lithotripsy is a highly successful, noninvasive, time-saving and easily applicable technique. It has become our primary approach in the treatment of distal ureteral calculi.

An Enzyme-Responsive "Turn-on" Fluorescence Polymeric Superamphiphile as a Potential Visualizable Phosphate Prodrug Delivery Vehicle.

PubMed

Yang, Xi; Shen, Shihong; Guo, Li; Tan, Jidong; Lei, Henxin; Wu, Jianghan; Zhao, Lei; Xiong, Tao; Wu, Youshen; Cheng, Yilong; Zhang, Yanfeng

2018-06-01

The development of inexpensive and highly efficient enzyme-responsive polymers has significantly contributed to targeted drug delivery systems. Here, a superamphiphile with a capability of fluorescent dissociation sensing is designed. It is constructed with negatively charged adenosine 5'-triphosphate (ATP) and negatively charged fluorescein diphosphate (FDP), which are used as fluorescence detection, and a cationic diblock copolymer methoxy-poly(ethylene glycol) 113 -b-poly(2-dimethyl-aminoethyl methacrylate) 70 . Upon addition of calf intestinal alkaline phosphatase, the superamphiphile disintegrates, presumably due to the enzymatic hydrolysis of ATP. This process is accompanied by an increase in the fluorescence emission intensity of fluorescein owing to the hydrolysis of FDP. The in vitro application of the superamphiphile is also proven. Thus, the "turn-on" fluorescence of the superamphiphile serves as a real-time module for detection of the disintegration of superamphiphile. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Childhood Disintegrative Disorder.

ERIC Educational Resources Information Center

Malhotra, Savita; Gupta, Nitin

1999-01-01

This article reviews what is known about childhood distintegrative disorder (CDD), a clinical syndrome characterized by disintegration of mental functions and regression of acquired language and intellectual functions after a period (usually 3-4 years) of normal development. It reviews the condition's epidemiology, onset and progression,…

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.

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.

Effects of the KIF2C neck peptide on microtubules: lateral disintegration of microtubules and β-structure formation.

PubMed

Shimizu, Youské; Shimizu, Takashi; Nara, Masayuki; Kikumoto, Mahito; Kojima, Hiroaki; Morii, Hisayuki

2013-04-01

Members of the kinesin-13 sub-family, including KIF2C, depolymerize microtubules. The positive charge-rich 'neck' region extending from the N-terminus of the catalytic head is considered to be important in the depolymerization activity. Chemically synthesized peptides, covering the basic region (A182-E200), induced a sigmoidal increase in the turbidity of a microtubule suspension. The increase was suppressed by salt addition or by reduction of basicity by amino acid substitutions. Electron microscopic observations revealed ring structures surrounding the microtubules at high peptide concentrations. Using the peptide A182-D218, we also detected free thin straight filaments, probably protofilaments disintegrated from microtubules. Therefore, the neck region, even without the catalytic head domain, may induce lateral disintegration of microtubules. With microtubules lacking anion-rich C-termini as a result of subtilisin treatment, addition of the peptide induced only a moderate increase in turbidity, and rings and protofilaments were rarely detected, while aggregations, also thought to be caused by lateral disintegration, were often observed in electron micrographs. Thus, the C-termini are not crucial for the action of the peptides in lateral disintegration but contribute to structural stabilization of the protofilaments. Previous structural studies indicated that the neck region of KIF2C is flexible, but our IR analysis suggests that the cation-rich region (K190-A204) forms β-structure in the presence of microtubules, which may be of significance with regard to the action of the neck region. Therefore, the neck region of KIF2C is sufficient to cause disintegration of microtubules into protofilaments, and this may contribute to the ability of KIF2C to cause depolymerization of microtubules. © 2013 The Authors Journal compilation © 2013 FEBS.

Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.

PubMed

Lin, Shan-Yang; Li, Mei-Jane; Lin, Kung-Hsu

2004-08-16

An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.

[Studies on preparation of sustained-release Shuxiong formulation, a traditional Chinese medicine compound recipe, using time-controlled release techniques].

PubMed

Song, Hong-Tao; Zhang, Qian; Jiang, Peng; Guo, Tao; Chen, Da-Wei; He, Zhong-Gui

2006-09-01

To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.

Disintegration of fluids under supercritical conditions from mixing layer studies

NASA Technical Reports Server (NTRS)

Okong'o, N.; Bellan, J.

2003-01-01

Databases of transitional states obtained from Direct Numerical simulations (DNS) of temporal, supercritical mixing layers for two species systems, O2/H2 and C7H16/N2, are analyzed to elucidate species-specific turbulence aspects and features of fluid disintegration.

High Functioning Autism and Childhood Disintegrative Disorder in Half Brothers.

ERIC Educational Resources Information Center

Zwaigenbaum, L.; Szatmari, P.; Mahoney, W.; Bryson, S.; Bartolucci, G.; MacLean, J.

2000-01-01

This case report describes the presence of autism and Childhood Disintegrative Disorder (CDD) cosegregating within a sibship of half-brothers with the same mother. The report suggests that the rarity of the two conditions suggests a shared transmissible mechanism. (Contains references.) (Author/DB)

Criteria for personal dosimetry in mixed radiation fields in space. [analyzing trapped protons, tissue disintegration stars, and neutrons

NASA Technical Reports Server (NTRS)

Schaefer, H. J.

1974-01-01

The complexity of direct reading and passive dosimeters for monitoring radiation is studied to strike the right balance of compromise to simplify the monitoring procedure. Trapped protons, tissue disintegration stars, and neutrons are analyzed.

Energy efficient bead milling of microalgae: Effect of bead size on disintegration and release of proteins and carbohydrates.

PubMed

Postma, P R; Suarez-Garcia, E; Safi, C; Yonathan, K; Olivieri, G; Barbosa, M J; Wijffels, R H; Eppink, M H M

2017-01-01

The disintegration of three industry relevant algae (Chlorella vulgaris, Neochloris oleoabundans and Tetraselmis suecica) was studied in a lab scale bead mill at different bead sizes (0.3-1mm). Cell disintegration, proteins and carbohydrates released into the water phase followed a first order kinetics. The process is selective towards proteins over carbohydrates during early stages of milling. In general, smaller beads led to higher kinetic rates, with a minimum specific energy consumption of ⩽0.47kWhkg DW -1 for 0.3mm beads. After analysis of the stress parameters (stress number and stress intensity), it appears that optimal disintegration and energy usage for all strains occurs in the 0.3-0.4mm range. During the course of bead milling, the native structure of the marker protein Rubisco was retained, confirming the mildness of the disruption process. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

H2O2 induced cost effective microwave disintegration of dairy waste activated sludge in acidic environment for efficient biomethane generation.

PubMed

Eswari, A Parvathy; Kavitha, S; Banu, J Rajesh; Karthikeyan, O Parthiba; Yeom, Ick-Tae

2017-11-01

This study aimed to improve the biomethane potential of dairy waste activated sludge (WAS) by H 2 O 2 -acidic pH induced microwave disintegration (HAMW-D) pretreatment approach. The results of HAMW-D compared with the microwave disintegration (MW-D) alone for energy and economic factors. In the two phase disintegration process, the H 2 O 2 concentration of about 0.5mg/g SS under acid pH of 5 was found to be optimum for effective dissociation of Extracellular Polymeric Substances (EPS) matrix. A higher liquefaction of about 46.6% was achieved in HAMW-D when compared to that of MW-D (30%). It subsequently improved the methane yield of about 250mL/g VS in HAMW-D, which was 9.6% higher than MW-D. A net profit of about 49€/ton was achieved for HAMW-D, therefore it is highly recommended for WAS pretreatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparing alkaline and thermal disintegration characteristics for mechanically dewatered sludge.

PubMed

Tunçal, Tolga

2011-10-01

Thermal drying is one of the advanced technologies ultimately providing an alternative method of sludge disposal. In this study, the drying kinetics of mechanically dewatered sludge (MDS) after alkaline and thermal disintegration have been studied. In addition, the effect of total organic carbon (TOC) on specific resistance to filtration and sludge bound water content were also investigated on freshly collected sludge samples. The combined effect of pH and TOC on the thermal sludge drying rate for MDS was modelled using the two-factorial experimental design method. Statistical assessment of the obtained results proposed that sludge drying potential has increased exponentially for both increasing temperature and lime dosage. Execution of curve fitting algorithms also implied that drying profiles for raw and alkaline-disintegrated sludge were well fitted to the Henderson and Pabis model. The activation energy of MDS decreased from 28.716 to 11.390 kJ mol(-1) after disintegration. Consequently, the unit power requirement for thermal drying decreased remarkably from 706 to 281 W g(-1) H2O.

Homogeneous suspensions of individualized microfibrils from TEMPO-catalyzed oxidation of native cellulose.

PubMed

Saito, Tsuguyuki; Nishiyama, Yoshiharu; Putaux, Jean-Luc; Vignon, Michel; Isogai, Akira

2006-06-01

Never-dried native celluloses (bleached sulfite wood pulp, cotton, tunicin, and bacterial cellulose) were disintegrated into individual microfibrils after oxidation mediated by the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical followed by a homogenizing mechanical treatment. When oxidized with 3.6 mmol of NaClO per gram of cellulose, almost the totality of sulfite wood pulp and cotton were readily disintegrated into long individual microfibrils by a treatment with a Waring Blendor, yielding transparent and highly viscous suspensions. When observed by transmission electron microscopy, the wood pulp and cotton microfibrils exhibited a regular width of 3-5 nm. Tunicin and bacterial cellulose could be disintegrated by sonication. A bulk degree of oxidation of about 0.2 per one anhydroglucose unit of cellulose was necessary for a smooth disintegration of sulfite wood pulp, whereas only small amounts of independent microfibrils were obtained at lower oxidation levels. This limiting degree of oxidation decreased in the following order: sulfite wood pulp > cotton > bacterial cellulose, tunicin.

Mitochondrial Ca2+ influx targets cardiolipin to disintegrate respiratory chain complex II for cell death induction

PubMed Central

Hwang, M-S; Schwall, C T; Pazarentzos, E; Datler, C; Alder, N N; Grimm, S

2014-01-01

Massive Ca2+ influx into mitochondria is critically involved in cell death induction but it is unknown how this activates the organelle for cell destruction. Using multiple approaches including subcellular fractionation, FRET in intact cells, and in vitro reconstitutions, we show that mitochondrial Ca2+ influx prompts complex II of the respiratory chain to disintegrate, thereby releasing an enzymatically competent sub-complex that generates excessive reactive oxygen species (ROS) for cell death induction. This Ca2+-dependent dissociation of complex II is also observed in model membrane systems, but not when cardiolipin is replaced with a lipid devoid of Ca2+ binding. Cardiolipin is known to associate with complex II and upon Ca2+ binding coalesces into separate homotypic clusters. When complex II is deprived of this lipid, it disintegrates for ROS formation and cell death. Our results reveal Ca2+ binding to cardiolipin for complex II disintegration as a pivotal step for oxidative stress and cell death induction. PMID:24948011

Profitable ultrasonic assisted microwave disintegration of sludge biomass: Modelling of biomethanation and energy parameter analysis.

PubMed

Kavitha, S; Rajesh Banu, J; Kumar, Gopalakrishnan; Kaliappan, S; Yeom, Ick Tae

2018-04-01

In this study, microwave irradiation has been employed to disintegrate the sludge biomass profitably by deagglomerating the sludge using a mechanical device, ultrasonicator. The outcomes of the study revealed that a specific energy input of 3.5 kJ/kg TS was found to be optimum for deagglomeration with limited cell lysis. A higher suspended solids (SS) reduction and biomass lysis efficiency of about 22.5% and 33.2% was achieved through ultrasonic assisted microwave disintegration (UMWD) when compared to microwave disintegration - MWD (15% and 20.9%). The results of biochemical methane potential (BMP) test were used to estimate biodegradability of samples. Among the samples subjected to BMP, UMWD showed better amenability towards anaerobic digestion with higher methane production potential of 0.3 L/g COD representing enhanced liquefaction potential of disaggregated sludge biomass. Economic analysis of the proposed method of sludge biomass pretreatment showed a net profit of 2.67 USD/Ton respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of the temperature on the cement disintegration in cement-retained implant restorations.

PubMed

Linkevicius, Tomas; Vindasiute, Egle; Puisys, Algirdas; Linkeviciene, Laura; Svediene, Olga

2012-01-01

The aim of this study was to estimate the average disintegration temperature of three dental cements used for the cementation of the implant-supported prostheses. One hundred and twenty metal frameworks were fabricated and cemented on the prosthetic abutments with different dental cements. After heat treatment in the dental furnace, the samples were set for the separation to test the integration of the cement. Results have shown that resin-modified glass-ionomer cement (RGIC) exhibited the lowest disintegration temperature (p<0.05), but there was no difference between zinc phosphate cement (ZPC) and dual cure resin cement (RC) (p>0.05). Average separation temperatures: RGIC - 306 ± 23 °C, RC - 363 ± 71 °C, it could not be calculated for the ZPC due to the eight unseparated specimens. Within the limitations of the study, it could be concluded that RGIC cement disintegrates at the lowest temperature and ZPC is not prone to break down after exposure to temperature.

Electromagnetically induced disintegration and polarization plane rotation of laser pulses

NASA Astrophysics Data System (ADS)

Parshkov, Oleg M.; Budyak, Victoria V.; Kochetkova, Anastasia E.

2017-04-01

The numerical simulation results of disintegration effect of linear polarized shot probe pulses of electromagnetically induced transparency in the counterintuitive superposed linear polarized control field are presented. It is shown, that this disintegration occurs, if linear polarizations of interacting pulses are not parallel or mutually perpendicular. In case of weak input probe field the polarization of one probe pulse in the medium is parallel, whereas the polarization of another probe pulse is perpendicular to polarization direction of input control radiation. The concerned effect is analogous to the effect, which must to take place when short laser pulse propagates along main axes of biaxial crystal because of group velocity of normal mod difference. The essential difference of probe pulse disintegration and linear process in biaxial crystal is that probe pulse preserves linear polarization in all stages of propagation. The numerical simulation is performed for scheme of degenerated quantum transitions between 3P0 , 3P01 and 3P2 energy levels of 208Pb isotope.

Stabilization Mechanism of Roxithromycin Tablets under Gastric pH Conditions.

PubMed

Inukai, Koki; Noguchi, Shuji; Kimura, Shin-Ichiro; Itai, Shigeru; Iwao, Yasunori

2018-05-31

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of three widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A (EM), and azithromycin (AZM). The results indicated that not only CAM but also RXM gelated under acidic conditions. EM and AZM did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that two of the four macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides. Copyright © 2018. Published by Elsevier Inc.

Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

PubMed

Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P; Parks, Thomas P

2015-01-01

MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

Robust Vaginal Colonization of Macaques with a Novel Vaginally Disintegrating Tablet Containing a Live Biotherapeutic Product to Prevent HIV Infection in Women

PubMed Central

Lagenaur, Laurel A.; Swedek, Iwona; Lee, Peter P.; Parks, Thomas P.

2015-01-01

MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody. PMID:25875100

Identification of the Properties of Gum Arabic Used as a Binder in 7.62-mm Ammunition Primers

DTIC Science & Technology

2010-06-01

Solution - LCC Testing (ATK Task 700) 51 Cartridge - Ballistic Testing (ATK Task 800) 51 ATK Elemental Analysis 52 Moisture Loss and Friability...Hummel sample 7 3 SDT summary for Quadra sample 8 4 Particle size analysis summary for gum arabic samples 9 5 SEM images of Colony gum arabic at 230x...strengths 21 16 Color analysis : Colony after 5.0 hrs 23 17 Color analysis : Hummel after 5.0 hrs 23 18 Color analysis : Brenntag after 5.0 hrs 23 19 Gel

EVIDENCE FOR GAS FROM A DISINTEGRATING EXTRASOLAR ASTEROID

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

Xu, S.; Jura, M.; Zuckerman, B.

We report high-resolution spectroscopic observations of WD 1145+017—a white dwarf that was recently found to be transitted by multiple asteroid-sized objects within its tidal radius. We discovered numerous circumstellar absorption lines with linewidths of ∼300 km s{sup −1} from Mg, Ca, Ti, Cr, Mn, Fe, and Ni, possibly from several gas streams produced by collisions among the actively disintegrating objects. The atmosphere of WD 1145+017 is polluted with 11 heavy elements, including O, Mg, Al, Si, Ca, Ti, V:, Cr, Mn, Fe, and Ni. Evidently, we are witnessing the active disintegration and subsequent accretion of an extrasolar asteroid.

Suicide in the Ukraine.

PubMed

Kondrichin, Sergei V; Lester, David

2002-01-01

The suicide rates of the 24 provinces (oblasts) of the Ukraine were found to be strongly associated with indices of social disintegration (such as divorce and illegitimacy rates), with the Western provinces incorporated in the USSR later than other Ukrainian territories having lower suicide rates and lower levels of social disintegration.

Case Study of Childhood Disintegrative Disorder--Heller's Syndrome.

ERIC Educational Resources Information Center

Bray, Melissa A.; Kehle, Thomas J.; Theodore, Lea A.; Broudy, Matthew S.

2002-01-01

Discusses the case of a 25-year-old male with childhood disintegrative disorder (CDD), or Heller's syndrome, in terms of differential diagnosis, progression of the disorder, and suggestions for home- and school-based interventions. Documents the progressive deterioration of cognitive and social competencies. (Contains 23 references.) (GCP)