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

PubMed Central

Vranić, Edina; Uzunović, Alija

2007-01-01

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

Design, formulation and evaluation of caffeine chewing gum.

PubMed

Aslani, Abolfazl; Jalilian, Fatemeh

2013-01-01

Caffeine which exists in drinks such as coffee as well as in drug dosage forms in the global market is among the materials that increase alertness and decrease fatigue. Compared to other forms of caffeine, caffeine gum can create faster and more prominent effects. In this study, the main goal is to design a new formulation of caffeine gum with desirable taste and assess its physicochemical properties. Caffeine gum was prepared by softening of gum bases and then mixing with other formulation ingredients. To decrease the bitterness of caffeine, sugar, aspartame, liquid glucose, sorbitol, manitol, xylitol, and various flavors were used. Caffeine release from gum base was investigated by mechanical chewing set. Content uniformity test was also performed on the gums. The gums were evaluated in terms of organoleptic properties by the Latin-Square design at different stages. After making 22 formulations of caffeine gums, F11 from 20 mg caffeine gums and F22 from 50 mg caffeine gums were chosen as the best formulation in organoleptic properties. Both types of gum released about 90% of their own drug content after 30 min. Drug content of 20 and 50 mg caffeine gum was about 18.2-21.3 mg and 45.7-53.6 mg respectively. In this study, 20 and 50 mg caffeine gums with suitable and desirable properties (i.e., good taste and satisfactory release) were formulated. The best flavor for caffeine gum was cinnamon. Both kinds of 20 and 50 mg gums succeeded in content uniformity test.

Design and in vivo evaluation of carvedilol buccal mucoadhesive patches.

PubMed

Thimmasetty, J; Pandey, G S; Babu, P R Sathesh

2008-07-01

The buccal region offers an attractive route of administration for systemic drug delivery. Carvedilol (dose, 3.125-25 mg) is beta-adrenergic antagonist. Its oral bioavailability is 25-35% because of first pass metabolism. Buccal absorption studies of a carvedilol solution in human volunteers showed 32.86% drug absorption. FTIR and UV spectroscopic methods revealed that there was no interaction between carvedilol and polymers. Carvedilol patches were prepared using HPMC, carbopol 934, eudragit RS 100, and ethylcellulose. The patches were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, swelling behaviour, tensile strength, and surface pH. In vitro release studies were conducted for carvedilol-loaded patches in phosphate buffer (pH, 6.6) solution. Patches exhibited drug release in the range of 86.26 to 98.32% in 90 min. Data of in vitro release from patches were fit to different equations and kinetic models to explain release profiles. Kinetic models used were zero and first-order equations, Hixon-Crowell, Higuchi, and Korsmeyer-Peppas models. In vivo drug release studies in rabbits showed 90.85% of drug release from HPMC-carbopol patch while it was 74.63 to 88.02% within 90 min in human volunteers. Good correlation among in vitro release and in vivo release of carvedilol was observed.

Evaluation of Granulated Lactose as a Carrier for Dry Powder Inhaler Formulations 2: Effect of Drugs and Drug Loading.

PubMed

Du, Ping; Du, Ju; Smyth, Hugh D C

2017-01-01

Previously, granulated lactose carriers were shown to improve uniformity and aerosolization of a low-dose model drug. In the present study, the blending uniformity and aerosol dispersion performance were assessed for 2 model drugs salbutamol sulfate (SS) and rifampicin (RIF), blended at high loadings (10% or 30% drug) with granulated lactose carriers. The model drug powders differed in particle size distribution, morphology, density, and surface energies. Content uniformity of RIF blends was better than that of SS. Aerosolization studies showed that all blend formulations had acceptable emitted fractions (>70%). The SS blends showed low induction-port deposition (6%-10%) compared to RIF (5%-30%). This difference was greater at high flow rates. At 90 L/min, the low induction port deposition of SS blends allowed high fine particle fraction (FPF) of 73%-81%, whereas the FPF of the RIF blends was around 43%-45% with higher induction port deposition. However, SS blends exhibited strong flow rate-dependent performance. Increasing the flow rate from 30 L/min to 90 L/min increased SS FPF from approximately 20% to 80%. Conversely, RIF blends were flow rate and drug loading independent. It was concluded that the aerosolization of high drug-loaded dry powder inhaler formulations using granulated lactose, particularly flow rate dependency, varies with active pharmaceutical ingredient properties. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug

PubMed Central

Alyami, Hamad; Dahmash, Eman; Bowen, James

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation. PMID:28609454

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug.

PubMed

Alyami, Hamad; Dahmash, Eman; Bowen, James; Mohammed, Afzal R

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.

Development and Evaluation of Cefadroxil Drug Loaded Biopolymeric Films Based on Chitosan-Furfural Schiff Base

PubMed Central

Dixit, Ritu B.; Uplana, Rahul A.; Patel, Vishnu A.; Dixit, Bharat C.; Patel, Tarosh S.

2010-01-01

Cefadroxil drug loaded biopolymeric films of chitosan-furfural schiff base were prepared by reacting chitosan with furfural in presence of acetic acid and perchloric acid respectively for the external use. Prepared films were evaluated for their strength, swelling index, thickness, drug content, uniformity, tensile strength, percent elongation, FTIR spectral analysis and SEM. The results of in vitro diffusion studies revealed that the films exhibited enhanced drug diffusion as compared to the films prepared using untreated chitosan. The films also demonstrated good to moderate antibacterial activities against selective gram positive and gram negative bacteria. PMID:21179325

Design, formulation and evaluation of caffeine chewing gum

PubMed Central

Aslani, Abolfazl; Jalilian, Fatemeh

2013-01-01

Background: Caffeine which exists in drinks such as coffee as well as in drug dosage forms in the global market is among the materials that increase alertness and decrease fatigue. Compared to other forms of caffeine, caffeine gum can create faster and more prominent effects. In this study, the main goal is to design a new formulation of caffeine gum with desirable taste and assess its physicochemical properties. Materials and Methods: Caffeine gum was prepared by softening of gum bases and then mixing with other formulation ingredients. To decrease the bitterness of caffeine, sugar, aspartame, liquid glucose, sorbitol, manitol, xylitol, and various flavors were used. Caffeine release from gum base was investigated by mechanical chewing set. Content uniformity test was also performed on the gums. The gums were evaluated in terms of organoleptic properties by the Latin-Square design at different stages. Results: After making 22 formulations of caffeine gums, F11 from 20 mg caffeine gums and F22 from 50 mg caffeine gums were chosen as the best formulation in organoleptic properties. Both types of gum released about 90% of their own drug content after 30 min. Drug content of 20 and 50 mg caffeine gum was about 18.2-21.3 mg and 45.7-53.6 mg respectively. Conclusion: In this study, 20 and 50 mg caffeine gums with suitable and desirable properties (i.e., good taste and satisfactory release) were formulated. The best flavor for caffeine gum was cinnamon. Both kinds of 20 and 50 mg gums succeeded in content uniformity test. PMID:24223387

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate, Cetirizine Hydrochloride in Combined Pharmaceutical Dosage Form: A New Era in Novel Drug Delivery for Pediatrics and Geriatrics

PubMed Central

Sharma, Deepak; Singh, Gurmeet; Kumar, Dinesh; Singh, Mankaran

2015-01-01

The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics. PMID:25810924

Colon targeted curcumin delivery using guar gum.

PubMed

Elias, Edwin J; Anil, Singhal; Ahmad, Showkat; Daud, Anwar

2010-06-01

Curcumin is used in the treatment of colon cancer, but its very poor absorption in the upper part of the GIT is a major concern. As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time and an increased responsiveness to absorption enhancers. The aim of the present study was to identify a suitable polymer (guar gum) based matrix tablet for curcumin with sufficient mechanical strength and promising in vitro mouth-to-colon release profile. Three formulations of curcumin were prepared using varying concentrations of guar gum containing 50 mg curcumin by the wet granulation method. Tablets were subjected to evaluation by studying parameter like hardness, friability, drug content uniformity, and in-vitro drug release. In vitro drug release was evaluated using simulated stomach, intestinal and colonic fluids. The susceptibility of guar gum to colonic bacteria was also assessed by a drug release study with rat caecal contents. The 40% guar gum containing formulation (F-1) showed better drug release (91.1%) after 24 hours in the presence of rat caecal contents in comparison with the 50% guar gum containing formulation (F-2) (82.1%). Curcumin could, thus, be positively delivered to the colon for effective colon cancer treatment using guar gum.

Development of sustained and dual drug release co-extrusion formulations for individual dosing.

PubMed

Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

2015-01-01

In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting.

PubMed

Zhang, Lin; Cao, Fengliang; Ding, Buyun; Li, Qilu; Xi, Yanwei; Zhai, Guangxi

2011-01-01

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit® S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit® S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.

Spectrofluorimetric determination of thioridazine and flupentixol in dosage forms; application to content uniformity test.

PubMed

Attia, Tamer Z; Omar, Mahmoud A

2016-08-01

A reliable, sensitive, cheap and non-extractive spectrofluorimetric method has been developed and validated for determination of thioridazine and flupentixol based on ternary complex formation with eosin and lead(II) in the presence of methylcellulose as surfactant at pH 3.2. Under the optimum conditions, the quantitative quenching effect of investigated drugs on the native fluorescence of eosin has been investigated. The quenching of the eosin fluorescence was measured at 517 nm after excitation at 462 nm. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized, and the results were satisfactory. The calibration plots were constructed over the range of 0.5-3.0 µg mL(-1) . The developed method was successfully applied for determination of investigated drugs in commercial tablets without interference from common excipients. It was further applied for content uniformity testing of flupentixol in its tablets. Statistical comparisons of the results with those of the reference methods revealed excellent agreement and indicated no significant difference in accuracy and precision. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Selective spectrofluorimetric method for determination of Lisinopril in pharmaceutical preparations and in presence of hydrochlorothiazide: Application to content uniformity testing.

PubMed

Derayea, Sayed M; Badr El-Din, Khalid M; Mohammed, Fatma F

2017-12-01

A novel sensitive and cost-effective spectrofluorimetric method has been developed and validated for determination of lisinopril (an angiotensin converting enzyme inhibitor) in its pure form and pharmaceutical preparations. The method is based on the reaction of the drug with ninhydrin and phenylacetaldehyde in buffered medium (pH 7.0) to form a highly fluorescent product measured at 460 nm after excitation at 390 nm. Different experimental parameters were optimized and calibration curve was constructed. The fluorescence-concentration relationship was linear in the range of 0.15-4.0 μg mL -1 . The calculated Limit of detection (LOD) and Limit of quantitation (LOQ) were 0.04 and 0.12 μg mL -1 , respectively. The method was successfully applied for the analysis of pharmaceutical preparations containing the studied drug either alone or co-formulated with hydrochlorothiazide. The obtained results were in agreement with those of the reported method in respect to accuracy and precession. Moreover, the method was applied content uniformity testing according to United States Pharmacopeia (USP) guidelines. Copyright © 2017 John Wiley & Sons, Ltd.

Investigation of product quality between extemporaneously compounded progesterone vaginal suppositories and an approved progesterone vaginal gel.

PubMed

Mahaguna, Vorapann; McDermott, J Mario; Zhang, Feng; Ochoa, Felipe

2004-01-01

The purpose of this investigation was to compare quality parameters, including product appearance, content uniformity, pH, weight uniformity, microbial limit testing and preservative effectiveness testing on extemporaneously compounded progesterone vaginal suppositories obtained from 10 randomly chosen compounding pharmacies (90 suppositories each) across the United States, to the Food and Drug Administration (FDA) approved prescription progesterone gel product (Prochieve/Crinone) which is manufactured in a cGMP regulated facility. The content uniformity and pH were determined using qualified methods. The microbial limits testing and preservative effectiveness testing were conducted according to compendial methods. Only one pharmacy provided suppositories that were all within the potency limits required for the prescription progesterone gel product. The other pharmacies provided at least some suppositories where progesterone content was either subpotent or superpotent for progesterone. The pH of most of the compounded suppository products was in the range of 4.22 to 7.68 with a median of 6.30 (normal vaginal pH is <5), whereas the gel product was 2.80. For compounded product from one of the pharmacies, microbial limits testing indicated CDC group IVC-2 and Comamonas acidovorans were detected. This data indicates that pharmacy compounded delivery systems for progesterone should be used with caution.

Actual Versus Expected Doses of Half Tablets Containing Prescribed Psychoactive Substances: A Systematic Review.

PubMed

Eserian, Jaqueline K; Lombardo, Márcia; Chagas, Jair R; Galduróz, José C F

2018-02-08

To assess through a systematic review of the literature if the practice of splitting tablets containing psychoactive/psychotropic medications for medical or economic reasons would result in the expected doses. A MEDLINE and PsycInfo comprehensive search of English-language publications from January 1999 to December 2015 was conducted using the terms describing tablet splitting (tablet splitting, split tablets, tablet subdivision, divided tablets, and half tablets) and psychoactive substances (psychoactive medicines, psychotropic medicines, antidepressants, anxiolytics, anticonvulsants, antipsychotics, and antiparkinsonian agents). An additional supplementary search included the references from the articles found. Studies were included if splitting content was directly related to psychoactive medications and examined the effect of tablet splitting on drug uniformity, weight uniformity, and adherence of psychoactive drugs. Articles were systematically reviewed and examined regarding the study design, methodology, and results of the study. A total of 125 articles were screened, and 13 were selected. Tablet splitting implications are extensive, yet substantial deviations from the ideal weight, potency, and dose uniformity are more prone to be important to patient safety. The uneven division of tablets might result in the administration of different doses than what was prescribed, causing under- or overdosing, which might be relevant depending on the drug. In 55% of the cases, splitting psychoactive drugs was satisfactory. It cannot be generalized that splitting psychoactive drugs compromises dose accuracy, thus tablet splitting might still be employed in cases in which the advantages outweigh the disadvantages. It is recommended that alternatives be adopted to prevent the disadvantages related to tablet splitting. © Copyright 2018 Physicians Postgraduate Press, Inc.

Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques.

PubMed

Genina, Natalja; Fors, Daniela; Vakili, Hossein; Ihalainen, Petri; Pohjala, Leena; Ehlers, Henrik; Kassamakov, Ivan; Haeggström, Edward; Vuorela, Pia; Peltonen, Jouko; Sandler, Niklas

2012-10-09

We combined conventional inkjet printing technology with flexographic printing to fabricate drug delivery systems with accurate doses and tailored drug release. Riboflavin sodium phosphate (RSP) and propranolol hydrochloride (PH) were used as water-soluble model drugs. Three different paper substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer. The printed APIs were coated with water insoluble polymeric films of different thickness using flexographic printing. All substrates were characterized with respect to wettability, surface roughness, air permeability, and cell toxicity. In addition, content uniformity and release profiles of the produced solid dosage forms before and after coating were studied. The substrates were nontoxic for the human cell line assayed. Substrate B was smoothest and least porous. The properties of substrates B and C were similar, whereas those of substrate A differed significantly from those of B, C. The release kinetics of both printed APIs was slowest from substrate B before and after coating with the water insoluble polymer film, following by substrate C, whereas substrate A showed the fastest release. The release rate decreased with increasing polymer coating film thickness. The printed solid dosage forms showed excellent content uniformity. So, combining the two printing technologies allowed fabricating controlled-release oral dosage forms that are challenging to produce using a single technique. The approach opens up new perspectives in the manufacture of flexible doses and tailored drug-delivery systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Simultaneous production and co-mixing of microparticles of nevirapine with excipients by supercritical antisolvent method for dissolution enhancement.

PubMed

Sanganwar, Ganesh P; Sathigari, Sateeshkumar; Babu, R Jayachandra; Gupta, Ram B

2010-01-31

Microparticles of a poorly water-soluble model drug, nevirapine (NEV) were prepared by supercritical antisolvent (SAS) method and simultaneously deposited on the surface of excipients such as lactose and microcrystalline cellulose in a single step to reduce drug-drug particle aggregation. In the proposed method, termed supercritical antisolvent-drug excipient mixing (SAS-DEM), drug particles were precipitated in supercritical CO(2) vessel containing excipient particles in suspended state. Drug/excipient mixtures were characterized for surface morphology, crystallinity, drug-excipient physico-chemical interactions, and molecular state of drug. In addition, the drug content uniformity and dissolution rate were determined. A highly ordered NEV-excipient mixture was produced. The SAS-DEM treatment was effective in overcoming drug-drug particle aggregation and did not affect the crystallinity or physico-chemical properties of NEV. The produced drug/excipient mixture has a significantly faster dissolution rate as compared to SAS drug microparticles alone or when physically mixed with the excipients. Copyright 2009 Elsevier B.V. All rights reserved.

Formulation and in vitro evaluation of Hydrodynamically balanced system for theophylline delivery.

PubMed

Nayak, Amit Kumar; Malakar, Jadupati

2011-06-01

The objective of the present study was to formulate hydrodynamically balanced systems (HBSs) of theophylline as single unit capsules. They were formulated by physical blending of theophylline with hydroxypropyl methyl cellulose, polyethylene oxide, polyvinyl pyrrolidone, ethyl cellulose, liquid paraffin, and lactose in different ratios. These theophylline HBS capsules were evaluated for weight uniformity, drug content uniformity, in vitro floating behavior and drug release in simulated gastric fluids (pH 1.2). All these formulated HBS capsules containing theophylline were floated well over 6 hours with no floating lag time, and also showed sustained in vitro drug release in simulated gastric fluid over 6 hours. The theophylline release from these capsules was more sustained with the addition of release modifiers (ethyl cellulose and liquid paraffin). The drug release pattern from these capsules was correlated well with first order model (F-1 to F-5) and Korsmeyer-Peppas model (F-6 and F-7) with the non-Fickian (anomalous) diffusion mechanism. These experimental results clearly indicated that these theophylline HBS capsules were able to remain buoyant in the gastric juice for longer period, which may improve oral bioavailability of theophylline.

Nifedipine capsules may provide a viable alternative to oral powders for paediatric patients.

PubMed

Helin-Tanninen, M; Naaranlahti, T; Kontra, K; Savolainen, K

2007-02-01

To compare content uniformities between different sizes of extemporaneously compounded nifedipine oral powders and capsules, in order to find out if capsules could be used instead of oral powders as paediatric medications. Actual content and content uniformity of extemporaneously compounded 1-mg nifedipine oral powders and capsules were evaluated by a high performance liquid chromatographic assay. Capsules and powders were prepared by triturating 10-mg nifedipine tablets with different amounts of lactose or microcrystalline cellulose with a mortar and pestle using a standard geometric dilution technique. Oral powders were weighed individually and capsules were filled by a hand-operated capsule-filling machine. Four different sizes of powders (500, 300, 100 and 50 mg) and three different sizes of capsules (numbers 1, 3 and 4) were prepared. Ten oral powders and 10 capsules from each batch were randomly selected and individually assayed for nifedipine amount. The extemporaneously prepared nifedipine oral powders and capsules were within acceptable limits for content uniformity, as defined by the European Pharmacopoeia, but the results indicate that the loss of nifedipine during the preparation process may be considerable for both preparations. The concentration on nifedipine decreased while the total mass of the oral powder decreased. These results demonstrate that nifedipine oral powders can be replaced by capsules, whose contents are emptied for use, in paediatric medications. Compounding small capsules, such as size number 3 or 4, is acceptable when considering the average drug content. The total weight of the oral powder should be at least 300 mg. The preparation of nifedipine in all studied capsule sizes was safe with either lactose monohydrate or microcrystalline cellulose as excipients. Thus, emptied capsules seem to be a good choice for delivering a paediatric medication. The loss of nifedipine was considerable in oral powders with low total weight.

Formulation and evaluation of dried yeast tablets using different techniques.

PubMed

Al-Mohizea, Abdullah M; Ahmed, Mahrous O; Al-jenoobi, Fahad I; Mahrous, Gamal M; Abdel-Rahman, Aly A

2007-08-01

The aim of this study was to prepare and evaluate dried yeast tablets using both direct compression and dry granulation techniques in comparison with the conventional wet granulation as well as commercial product. Wet granulation technique is not favorable for producing the yeast tablets due to the problems of color darkening and the reduction of the fermentation power of the yeast as a result of the early start of the fermentation process due to the presence of moisture. Twenty six formulae of dried yeast tablets were prepared and evaluated. Certain directly compressible vehicles were employed for preparing these tablets. The quality control tests (weight uniformity, friability, disintegration time and hardness) of the prepared dried yeast tablets were performed according to B.P. 1998 limits. All batches of the prepared tablets complied with the B.P. limits of weight uniformity. Moreover, small values of friability % (1% or less) were obtained for all batches of dried yeast tablets with acceptable hardness values, indicating good mechanical properties which can withstand handling. On the other hand, not all batches complied with the limit of disintegration test which may be attributed to various formulation component variables. Therefore, four disintegrating agents were investigated for their disintegrating effect. It was found that the method of preparation, whether it is direct compression, dry granulation or wet granulation, has an effect on disintegration time of these dried yeast tablets and short disintegration times were obtained for some of the formulae. The shortest disintegration time was obtained with those tablets prepared by direct compression among the other techniques. Therefore, the direct compression is considered the best technique for preparation of dried yeast tablets and the best formula (which showed shorter disintegration time and better organoleptic properties than the available commercial yeast tablets) was chosen. Drug content for dried yeast granular powder, and the chosen best prepared formula, was determined by gas chromatography (GC). It was found that this formula gave the same alcohol content produced by an equal amount of the dried yeast granular powder. This result in conjunction with weight uniformity indicated drug content uniformity of the prepared dried yeast tablets.

Salbutamol sulfate suppositories: influence of formulation on physical parameters and stability.

PubMed

Taha, Ehab I; Zaghloul, Abdel-Azim A; Kassem, Alaa A; Khan, Mansoor A

2003-01-01

To prepare and evaluate a suppository dosage form of salbutamol sulfate. The prepared formulae with and without different concentrations of gels were tested for hardness, melting time, content uniformity, and drug release. The stability of some of the selected formulae was assessed. Salbutamol sulfate was formulated as a rectal suppository with emulsifying fatty bases (suppocire and witepsol) and water-soluble bases (PEG) adopting the molding from a melt technique. Physical characteristics and dissolution profiles of the prepared formulations were determined as the responses. The effects of adding gels, methyl cellulose (MC), and Eudispert (Eud) and their concentrations (1, 3, and 6%) on these responses were also investigated. Formulations showing high rank order were scaled up for shelf-life stability study for one year. The results showed that all the investigated formulae have acceptable physical characteristics with respect to hardness, melting time (except F7), and uniformity of drug content. The amount of drug dissolved in 100 min of dissolution time was inversely affected by the melting point of the fatty base. The release from PEG bases was found to be molecular weight dependent. Addition of 1% MC or Eud gel increased the release from all the investigated formulae. Increasing gel concentration to 3% then to 6% showed different effects on the release. The degradation of salbutamol sulfate in the investigated formulae was found to be a first-order reaction. Rectal suppository of salbutamol sulfate could be prepared as an alternative to the oral dosage form to circumvent the first-pass metabolism.

Analysis of the Uniform Accident And Sickness Policy Provision Law: lessons for social work practice, policy, and research.

PubMed

Cochran, Gerald

2010-01-01

The Uniform Accident and Sickness Policy Provision Law (UPPL) is a state statute that allows insurance companies in 26 states to deny claims for accidents and injuries incurred by persons under the influence of drugs or alcohol. Serious repercussions can result for patients and health care professionals as states enforce this law. To examine differences within the laws that might facilitate amendments or reduce insurance companies' ability to deny claims, a content analysis was carried out of each state's UPPL law. Results showed no meaningful differences between each state's laws. These results indicate patients and health professionals share similar risk related to the UPPL regardless of state.

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.

[Preparation of ondansetron hydrochloride osmotic pump tablets and their in vitro drug release].

PubMed

Zheng, Hang-sheng; Bi, Dian-zhou

2005-12-01

To prepare ondansetron hydrochloride osmotic pump tablets (OND-OPT) and investigate their in vitro drug release behavior. OND-OPT were prepared with a single punch press and pan coating technique. Osmotic active agents and plasticizer of coating film were chosen by drug release tests. The effects of the number, position and direction of drug release orifice on release behavior were investigated. The relation between drug release duration and thickness of coating film, PEG content of coating film and size of drug release orifice was established by uniform design experiment. The surface morphological change of coating film before and after drug release test was observed by scanning electron microscopy. The osmotic pumping release mechanism of OND-OPT was confirmed by drug release test with high osmotic pressure medium. Lactose-mannitol (1:2) was chosen as osmotic active agents and PEG400 as plasticizer of coating film. The direction of drug release orifice had great effect on the drug release of OND-OPT without HPMC, and had no effect on the drug release of OND-OPT with HPMC. The OND-OPT with one drug release orifice at the centre of the coating film on one surface of tablet released their drug with little fluctuation. The drug release duration of OND-OPT correlated with thickness of coating film and PEG content of coating film, and didn't correlate significantly with the size of drug release orifice. OND-OPT released their drug with osmotic pumping mechanism predominantly. OND-OPT are able to realize ideal controlled drug release.

A cross-sectional investigation of the quality of selected medicines in Cambodia in 2010

PubMed Central

2014-01-01

Background Access to good-quality medicines in many countries is largely hindered by the rampant circulation of spurious/falsely labeled/falsified/counterfeit (SFFC) and substandard medicines. In 2006, the Ministry of Health of Cambodia, in collaboration with Kanazawa University, Japan, initiated a project to combat SFFC medicines. Methods To assess the quality of medicines and prevalence of SFFC medicines among selected products, a cross-sectional survey was carried out in Cambodia. Cefixime, omeprazole, co-trimoxazole, clarithromycin, and sildenafil were selected as candidate medicines. These medicines were purchased from private community drug outlets in the capital, Phnom Penh, and Svay Rieng and Kandal provinces through a stratified random sampling scheme in July 2010. Results In total, 325 medicine samples were collected from 111 drug outlets. Non-licensed outlets were more commonly encountered in rural than in urban areas (p < 0.01). Of all the samples, 93.5% were registered and 80% were foreign products. Samples without registration numbers were found more frequently among foreign-manufactured products than in domestic ones (p < 0.01). According to pharmacopeial analytical results, 14.5%, 4.6%, and 24.6% of the samples were unacceptable in quantity, content uniformity, and dissolution test, respectively. All the ultimately unacceptable samples in the content uniformity tests were of foreign origin. Following authenticity investigations conducted with the respective manufacturers and medicine regulatory authorities, an unregistered product of cefixime collected from a pharmacy was confirmed as an SFFC medicine. However, the sample was acceptable in quantity, content uniformity, and dissolution test. Conclusions The results of this survey indicate that medicine counterfeiting is not limited to essential medicines in Cambodia: newer-generation medicines are also targeted. Concerted efforts by both domestic and foreign manufacturers, wholesalers, retailers, and regulatory authorities should help improve the quality of medicines. PMID:24593851

Preparation of mucoadhesive oral patches containing tetracycline hydrochloride and carvacrol for treatment of local mouth bacterial infections and candidiasis.

PubMed

Obaidat, Rana M; Bader, Ammar; Al-Rajab, Wafa; Abu Sheikha, Ghassan; Obaidat, Aiman A

2011-01-01

The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability.

Design of FLT3 Inhibitor - Gold Nanoparticle Conjugates as Potential Therapeutic Agents for the Treatment of Acute Myeloid Leukemia.

PubMed

Simon, Timea; Tomuleasa, Ciprian; Bojan, Anca; Berindan-Neagoe, Ioana; Boca, Sanda; Astilean, Simion

2015-12-01

Releasing drug molecules at the targeted location could increase the clinical outcome of a large number of anti-tumor treatments which require low systemic damage and low side effects. Nano-carriers of drugs show great potential for such task due to their capability of accumulating and releasing their payload specifically, at the tumor site. FLT3 inhibitor - gold nanoparticle conjugates were fabricated to serve as vehicles for the delivery of anti-tumor drugs. Lestaurtinib, midostaurin, sorafenib, and quizartinib were selected among the FLT3 inhibitor drugs that are currently used in clinics for the treatment of acute myeloid leukemia. The drugs were loaded onto nanoparticle surface using a conjugation strategy based on hydrophobic-hydrophobic interactions with the Pluronic co-polymer used as nanoparticle surface coating. Optical absorption characterization of the particles in solution showed that FLT3 inhibitor-incorporated gold nanoparticles were uniformly distributed and chemically stable regardless of the drug content. Drug loading study revealed a high drug content in the case of midostaurin drug which also showed increased stability. Drug release test in simulated cancer cell conditions demonstrated more than 56 % release of the entrapped drug, a result that correlates well with the superior cytotoxicity of the nano-conjugates comparatively with the free drug. This is a pioneering study regarding the efficient loading of gold nanoparticles with selected FLT3 inhibitors. In vitro cytotoxicity assessment shows that FLT3-incorporated gold nanoparticles are promising candidates as vehicles for anti-tumor drugs and demonstrate superior therapeutic effect comparatively with the bare drugs.

Formulation of thermoresponsive and buccal adhesive in situ gel for treatment of oral thrush containing poorly water soluble drug bifonazole.

PubMed

Patel, Dimendra; Patel, Dipti; Prajapati, Jatin; Patel, Umang; Patel, Vijay

2012-03-01

The aim of the present work is to formulate and evaluate in situ oral topical gels of poorly water soluble drug Bifonazole based on temperature induced systems for the treatment of oral candidiasis. Bifonazole is poorly water soluble and low permeable drug means it's belongs to BCS Class IV. Due to its poor water solubility, it necessary to enhance solubility in water by make complex with Beta- Cyclodextrin (Drug to βCyclo Dextrine ratio is 1:1). After in situ gel preparation done by using Poloxamer (10% and 15%w/w) along with carbopol 934 (0.2 to 1.0% w/w) and Bifonazole - β CD complex (1%w/w). The formulations were evaluated for physiochemical parameter, gelation Temperature, viscosity, gel strength, content uniformity mucoadhesive force, Diffusion Study.

Formulation of thermoresponsive and buccal adhesive in situ gel for treatment of oral thrush containing poorly water soluble drug bifonazole

PubMed Central

Patel, Dimendra; Patel, Dipti; Prajapati, Jatin; Patel, Umang; Patel, Vijay

2012-01-01

The aim of the present work is to formulate and evaluate in situ oral topical gels of poorly water soluble drug Bifonazole based on temperature induced systems for the treatment of oral candidiasis. Bifonazole is poorly water soluble and low permeable drug means it's belongs to BCS Class IV. Due to its poor water solubility, it necessary to enhance solubility in water by make complex with Beta- Cyclodextrin (Drug to βCyclo Dextrine ratio is 1:1). After in situ gel preparation done by using Poloxamer (10% and 15%w/w) along with carbopol 934 (0.2 to 1.0% w/w) and Bifonazole – β CD complex (1%w/w). The formulations were evaluated for physiochemical parameter, gelation Temperature, viscosity, gel strength, content uniformity mucoadhesive force, Diffusion Study. PMID:23066185

Quality control of anti-tuberculosis FDC formulations in the global market: part II-accelerated stability studies.

PubMed

Ashokraj, Y; Kohli, G; Kaul, C L; Panchagnula, R

2005-11-01

To determine the quality and performance of rifampicin (RMP) containing fixed-dose combination (FDC) formulations of anti-tuberculosis drugs sourced from the international market with respect to physical, chemical and dissolution properties after storage at accelerated stability conditions (40 degrees C/75% relative humidity) and to identify appropriate storage specifications. Formulations across different companies and combinations were subjected to 6-month accelerated stability testing in packaging conditions recommended by the manufacturer. Various pharmacopeial and nonpharmacopeial tests for tablets were performed for 3- and 6-month samples. All the formulations were found to be stable, where extent of dissolution was within +/- 10% of that of the initial value, and all formulations passed the pharmacopeial limits for assay and content uniformity of 90-110% and +/- 15% of average drug content, respectively. Good quality RMP-containing FDCs that remain stable after 6-month accelerated stability testing are available in the marketplace.

Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI).

PubMed

Yu, Tao; Chan, Kannie W Y; Anonuevo, Abraham; Song, Xiaolei; Schuster, Benjamin S; Chattopadhyay, Sumon; Xu, Qingguo; Oskolkov, Nikita; Patel, Himatkumar; Ensign, Laura M; van Zjil, Peter C M; McMahon, Michael T; Hanes, Justin

2015-02-01

Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging ("theranostics"). Here, we describe liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, e.g., the diaCEST MRI contrast agent barbituric acid (BA). We observed that polyethylene glycol (PEG)-coated liposomes containing ≥7 mol% PEG diffused only ~10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol%-PEG liposomes contained sufficient BA loading for diaCEST contrast, and provided improved vaginal distribution compared to 0 and 3mol%-PEG liposomes. However, increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution, suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol%-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces. This team of authors characterized liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, such as barbituric acid (a diaCEST MRI contrast agent) and concluded that liposomal MPP with optimized PEG coating enables drug delivery and imaging at mucosal surfaces. Copyright © 2015 Elsevier Inc. All rights reserved.

Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

PubMed

Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

2011-01-01

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

Development and validation of an UPLC method for determination of content uniformity in low-dose solid drugs products using the design space approach.

PubMed

Oliva, Alexis; Fariña, José B; Llabrés, Matías

2013-10-15

A simple and reproducible UPLC method was developed and validated for the quantitative analysis of finasteride in low-dose drug products. Method validation demonstrated the reliability and consistency of analytical results. Due to the regulatory requirements of pharmaceutical analysis in particular, evaluation of robustness is vital to predict how small variations in operating conditions affect the responses. Response surface methodology as an optimization technique was used to evaluate the robustness. For this, a central composite design was implemented around the nominal conditions. Statistical treatment of the responses (retention factor and drug concentrations expressed as percentage of label claim) showed that methanol content in mobile-phase and flow rate were the most influential factors. In the optimization process, the compromise decision support problem (cDSP) strategy was used. Construction of the robust domain from response-surfaces provided tolerance windows for the factors affecting the effectiveness of the method. The specified limits for the USP uniformity of dosage units assay (98.5-101.5%) and the purely experimental variations based on the repeatability test for center points (nominal conditions repetitions) were used as criteria to establish the tolerance windows, which allowed definition design space (DS) of analytical method. Thus, the acceptance criteria values (AV) proposed by the USP-uniformity of assay only depend on the sampling error. If the variation in the responses corresponded to approximately twice the repeatability standard deviation, individual values for percentage label claim (%LC) response may lie outside the specified limits; this implies the data are not centered between the specified limits, and that this term plus the sampling error affects the AV value. To avoid this fact, the limits specified by the Uniformity of Dosage Form assay (i.e., 98.5-101.5%) must be taken into consideration to fix the tolerance windows for each factor. All these results were verified by the Monte Carlo simulation. In conclusion, the level of variability for different factors must be calculated for each case, and not arbitrary way, provided a variation is found higher than the repeatability for center points and secondly, the %LC response must lie inside the specified limits i.e., 98.5-101.5%. If not the UPLC method must be re-developed. © 2013 Elsevier B.V. All rights reserved.

How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

PubMed

Hancock, Bruno C; Garcia-Munoz, Salvador

2013-03-01

Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data. The data from the PQRI industry survey do not support the commonly held viewpoint that granulation processes are necessary to create and sustain tablet and capsule formulations with a high degree of API uniformity. There was no correlation between the blend or tablet potency variability and the type of process used to manufacture the product. Although it is commonly believed that direct compression processes should be avoided for low API loading formulations because of blend and tablet content uniformity concerns, the data for direct compression processes reported by the respondents to the PQRI survey suggest that such processes are being used routinely to manufacture solid dosage forms of acceptable quality even when the drug loading is quite low. Copyright © 2012 Wiley Periodicals, Inc.

Establishing a Link Between Prescription Drug Abuse and Illicit Online Pharmacies: Analysis of Twitter Data.

PubMed

Katsuki, Takeo; Mackey, Tim Ken; Cuomo, Raphael

2015-12-16

Youth and adolescent non-medical use of prescription medications (NUPM) has become a national epidemic. However, little is known about the association between promotion of NUPM behavior and access via the popular social media microblogging site, Twitter, which is currently used by a third of all teens. In order to better assess NUPM behavior online, this study conducts surveillance and analysis of Twitter data to characterize the frequency of NUPM-related tweets and also identifies illegal access to drugs of abuse via online pharmacies. Tweets were collected over a 2-week period from April 1-14, 2015, by applying NUPM keyword filters for both generic/chemical and street names associated with drugs of abuse using the Twitter public streaming application programming interface. Tweets were then analyzed for relevance to NUPM and whether they promoted illegal online access to prescription drugs using a protocol of content coding and supervised machine learning. A total of 2,417,662 tweets were collected and analyzed for this study. Tweets filtered for generic drugs names comprised 232,108 tweets, including 22,174 unique associated uniform resource locators (URLs), and 2,185,554 tweets (376,304 unique URLs) filtered for street names. Applying an iterative process of manual content coding and supervised machine learning, 81.72% of the generic and 12.28% of the street NUPM datasets were predicted as having content relevant to NUPM respectively. By examining hyperlinks associated with NUPM relevant content for the generic Twitter dataset, we discovered that 75.72% of the tweets with URLs included a hyperlink to an online marketing affiliate that directly linked to an illicit online pharmacy advertising the sale of Valium without a prescription. This study examined the association between Twitter content, NUPM behavior promotion, and online access to drugs using a broad set of prescription drug keywords. Initial results are concerning, as our study found over 45,000 tweets that directly promoted NUPM by providing a URL that actively marketed the illegal online sale of prescription drugs of abuse. Additional research is needed to further establish the link between Twitter content and NUPM, as well as to help inform future technology-based tools, online health promotion activities, and public policy to combat NUPM online.

Establishing a Link Between Prescription Drug Abuse and Illicit Online Pharmacies: Analysis of Twitter Data

PubMed Central

Cuomo, Raphael

2015-01-01

Background Youth and adolescent non-medical use of prescription medications (NUPM) has become a national epidemic. However, little is known about the association between promotion of NUPM behavior and access via the popular social media microblogging site, Twitter, which is currently used by a third of all teens. Objective In order to better assess NUPM behavior online, this study conducts surveillance and analysis of Twitter data to characterize the frequency of NUPM-related tweets and also identifies illegal access to drugs of abuse via online pharmacies. Methods Tweets were collected over a 2-week period from April 1-14, 2015, by applying NUPM keyword filters for both generic/chemical and street names associated with drugs of abuse using the Twitter public streaming application programming interface. Tweets were then analyzed for relevance to NUPM and whether they promoted illegal online access to prescription drugs using a protocol of content coding and supervised machine learning. Results A total of 2,417,662 tweets were collected and analyzed for this study. Tweets filtered for generic drugs names comprised 232,108 tweets, including 22,174 unique associated uniform resource locators (URLs), and 2,185,554 tweets (376,304 unique URLs) filtered for street names. Applying an iterative process of manual content coding and supervised machine learning, 81.72% of the generic and 12.28% of the street NUPM datasets were predicted as having content relevant to NUPM respectively. By examining hyperlinks associated with NUPM relevant content for the generic Twitter dataset, we discovered that 75.72% of the tweets with URLs included a hyperlink to an online marketing affiliate that directly linked to an illicit online pharmacy advertising the sale of Valium without a prescription. Conclusions This study examined the association between Twitter content, NUPM behavior promotion, and online access to drugs using a broad set of prescription drug keywords. Initial results are concerning, as our study found over 45,000 tweets that directly promoted NUPM by providing a URL that actively marketed the illegal online sale of prescription drugs of abuse. Additional research is needed to further establish the link between Twitter content and NUPM, as well as to help inform future technology-based tools, online health promotion activities, and public policy to combat NUPM online. PMID:26677966

Medical Advice from Lawyers: A Content Analysis of Advertising for Drug Injury Lawsuits.

PubMed

Tippett, Elizabeth

2015-01-01

This study examined the medical information contained in a sample of television ads soliciting consumers for lawsuits against drug and medical device manufactures. Almost all such ads involved drugs or devices that have not been recalled and remain on the market. These ads raise important public health questions because they may influence the prospective medical decisions of viewers. The ads contained extensive descriptions of serious adverse events associated with the drugs or devices but almost uniformly failed to disclose information relating to the likelihood of such events. They also failed to effectively advise viewers to consult a doctor. Results also identified a subset of ads that mimicked public service announcements, claiming to be. a "medical alert" "consumer alert" or "FDA warning" at the start of the ad. Most such ads did not disclose the attorney source of the advertising until the final few seconds.

Design and Evaluation of Topical Diclofenac Sodium Gel Using Hot Melt Extrusion Technology as a Continuous Manufacturing Process with Kolliphor® P407.

PubMed

Pawar, Jaywant; Narkhede, Rajkiran; Amin, Purnima; Tawde, Vaishali

2017-08-01

The aim of the present context was to develop and evaluate a Kolliphor® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as an industrially feasible and continuous manufacturing technology for the manufacturing of gel formulation using Kolliphor® P407 and Kollisolv® PEG400 as a gel base. Diclofenac sodium was used as a model drug. The HME parameters such as feeding rate, screw speed, and barrel temperature were crucial for the semisolid product development, and were optimized after preliminary trials. For the processing of the gel formulation by HME, a modified screw design was used to obtain a uniform product. The obtained product was evaluated for physicochemical characterization such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), pH measurement, rheology, surface tension, and texture profile analysis. Moreover, it was analyzed for general appearance, spreadibility, surface morphology, and drug content. The optimized gel formulation showed homogeneity and transparent film when applied on a glass slide under microscope, pH was 7.02 and uniform drug content of 100.04 ± 2.74 (SD = 3). The DSC and XRD analysis of the HME gel formulation showed complete melting of crystalline API into an amorphous form. The Kolliphor® P407 and Kollisolv® PEG400 formed excellent gel formulation using HME with consistent viscoelastic properties of the product. An improved drug release was found for the HME gel, which showed a 100% drug release than that of a marketed product which showed only 88% of drug release at the end of 12 h. The Flux value of the HME gel was 106 than that of a marketed formulation, which showed only about 60 value, inferring a significant difference (P < 0.05) at the end of 1 h. This study demonstrates a novel application of the hot melt extrusion process for manufacturing of topical semisolid products.

Assessment of the pharmaceutical quality of marketed enteric coated pantoprazole sodium sesquihydrate products.

PubMed

Mostafa, Haitham F; Ibrahim, Mohamed A; Mahrous, Gamal M; Sakr, Adel

2011-04-01

Pantoprazole sodium sesquihydrate (PSS) is a proton pump inhibitor, used in acid-related disorders, like peptic ulcer and gastroesophageal reflux. Increasing the number of pantoprazole containing products in the market, raises questions of its efficacy and generic substitution. The pharmaceutical quality of 6 generic PSS enteric coated tablets in 2 local markets was assessed relative to the innovator product (pantozol®). Uniformity of dosage unit, disintegration and in vitro drug release were determined using United States pharmacopeia for delayed release tablets. The similarity factor (f2) was assessed using the FDA recommended approach (f2 similarity factor). The content uniformity of the innovator product was 98.39% of the labeled claim with RSD value of 1.08%, while the content of generic products ranged from 96.98% to 98.80% with RSD values of 1.24-2.19%. All the products showed no disintegration, cracks or swelling in 0.1 N HCl, except product 1, which showed complete disintegration after 20 min. However, the disintegration of all the products in phosphate buffer met USP requirements. Dissolution of tablets in 0.1 N HCl showed no drug release after 2 h except product 1 in which one tablet showed a drug release more than 10% at acid stage level A1. In addition, three tablets of this product showed dissolution of 45%, 48% and 69% at acid stage level A2. The similarity factor f2 of the products was between 71 and 74 indicating the similarity in dissolution profiles of all the products in accordance to FDA requirements, except product 1 in which f2 value was 18.67.

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

PubMed

Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

2010-01-01

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

A minitablet formulation made from electrospun nanofibers.

PubMed

Poller, Bettina; Strachan, Clare; Broadbent, Roland; Walker, Greg F

2017-05-01

The purpose of this study was to evaluate electrospun drug loaded nanofibers as a new matrix for minitablets. Prednisone, a poorly water-soluble drug, was loaded into povidone (polyvinylpyrrolidone, PVP) nanofibers using the process of electrospinning. The drug-loaded nanofiber mat was compressed into minitablets with a 2mm diameter and a height of 2.63±0.04mm. SEM analysis of the minitablet identified a nano-web structure with a nanofiber diameter in the range of 400-500nm. The minitablets met the requirements of the US Pharmacopeia with respect to content uniformity and friability. DSC and XRPD analysis of the minitablet indicated that the drug-polymer mixture was a one-phase amorphous system. XRPD analysis of the drug loaded nanofiber mat after 10-months of storage at ambient temperature showed no evidence of recrystallization of the drug. Solubility and dissolution properties of the drug formulated into a nanofiber mat and minitablet were evaluated. These results show that electrospun nanofibers may provide a useful matrix for the further development of minitablets. Copyright © 2017 Elsevier B.V. All rights reserved.

A knowledge management system for new drug submission by pharma-industries.

PubMed

Pinciroli, Francesco; Mottadelli, Sara; Vinci, Maurizio; Fabbro, Luigi; Gothager, Klas

2004-01-01

The pharma-industries are facing a number of crucial business issues to improve operational excellence in product time-to-market and wide regulatory compliance. These organizations own, produce, and manipulate a lot of knowledge. The new regulations by Health Authorities (HA) to pharma-industries should make the content and format of new drug application uniform worldwide. In this paper we suggest a novel approach of a pharma-industry to capture, process, and transmit clinical data electronically. The approach begins with an analysis of the knowledge generation points, some of them being outside the company. Implementations are grounded on the use of a de facto standard platform being Microsoft, having acceptable cost levels. The proposed infrastructure is integrated into existing company environment and technological platform, minimizing cost and risks, but improving efficiency and efficacy of new drug dossier compilation.

Microemulsion-loaded hydrogel formulation of butenafine hydrochloride for improved topical delivery.

PubMed

Pillai, Anilkumar B; Nair, Jyothilaksmi V; Gupta, Nishant Kumar; Gupta, Swati

2015-09-01

Topical microemulsion systems for the antifungal drug, butenafine hydrochloride (BTF) were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of BTF in oils, surfactants and co-surfactants was evaluated to screen the components of the microemulsion. Isopropyl palmitate was used as the oil phase, aerosol OT as the surfactant and sorbitan monooleate as co-surfactant. The pseudoternary diagrams were constructed to identify the area of microemulsion existence and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterized for pH, robustness to dilution, globule size, drug content and stability. Viscosity analysis, spreadability, drug content assay, ex vivo skin permeation study and antifungal activity assay were performed for the optimized microemulsion-loaded hydrogel. The optimized BTF microemulsion had a small and uniform globule size. The incorporation of microemulsion system into Carbopol 940 gel was found to be better as compared to sodium alginate or hydroxyl propyl methyl cellulose (HPMC K4 M) gel. The developed gel has shown better ex vivo skin permeation and antifungal activity when compared to marketed BTF cream. Thus, the results provide a basis for the successful delivery of BTF from microemulsion-loaded hydrogel formulation, which resulted in improved penetration of drug and antifungal activity in comparison with commercial formulation of BTF.

Single-step preparation and deagglomeration of itraconazole microflakes by supercritical antisolvent method for dissolution enhancement.

PubMed

Sathigari, Sateesh Kumar; Ober, Courtney A; Sanganwar, Ganesh P; Gupta, Ram B; Babu, R Jayachandra

2011-07-01

Itraconazole (ITZ) microflakes were produced by supercritical antisolvent (SAS) method and simultaneously mixed with pharmaceutical excipients in a single step to prevent drug agglomeration. Simultaneous ITZ particle formation and mixing with fast-flo lactose (FFL) was performed in a high-pressure stirred vessel at 116 bar and 40 °C by the SAS-drug excipient mixing (SAS-DEM) method. The effects of stabilizers, such as sodium dodecyl sulfate and poloxamer 407 (PLX), on particle formation and drug dissolution were studied. Drug-excipient formulations were characterized for surface morphology, crystallinity, drug-excipient interactions, drug content uniformity, and drug dissolution rate. Mixture of drug microflakes and FFL formed by the SAS-DEM process shows that the process was successful in overcoming drug-drug agglomeration. PLX produced crystalline drug flakes in loose agglomerates with superior dissolution and flow properties even at higher drug loadings. Characterization studies confirmed the crystallinity of the drug and absence of chemical interactions during the SAS process. The dissolution of ITZ was substantially higher due to SAS and SAS-DEM processes; this improvement can be attributed to the microflake particle structures, effective deagglomeration, and wetting of the drug flakes with the excipients. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

High-Content Monitoring of Drug Effects in a 3D Spheroid Model

PubMed Central

Mittler, Frédérique; Obeïd, Patricia; Rulina, Anastasia V.; Haguet, Vincent; Gidrol, Xavier; Balakirev, Maxim Y.

2017-01-01

A recent decline in the discovery of novel medications challenges the widespread use of 2D monolayer cell assays in the drug discovery process. As a result, the need for more appropriate cellular models of human physiology and disease has renewed the interest in spheroid 3D culture as a pertinent model for drug screening. However, despite technological progress that has significantly simplified spheroid production and analysis, the seeming complexity of the 3D approach has delayed its adoption in many laboratories. The present report demonstrates that the use of a spheroid model may be straightforward and can provide information that is not directly available with a standard 2D approach. We describe a cost-efficient method that allows for the production of an array of uniform spheroids, their staining with vital dyes, real-time monitoring of drug effects, and an ATP-endpoint assay, all in the same 96-well U-bottom plate. To demonstrate the method performance, we analyzed the effect of the preclinical anticancer drug MLN4924 on spheroids formed by VCaP and LNCaP prostate cancer cells. The drug has different outcomes in these cell lines, varying from cell cycle arrest and protective dormancy to senescence and apoptosis. We demonstrate that by using high-content analysis of spheroid arrays, the effect of the drug can be described as a series of EC50 values that clearly dissect the cytostatic and cytotoxic drug actions. The method was further evaluated using four standard cancer chemotherapeutics with different mechanisms of action, and the effect of each drug is described as a unique multi-EC50 diagram. Once fully validated in a wider range of conditions, this method could be particularly valuable for phenotype-based drug discovery. PMID:29322028

Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis.

PubMed

Goyal, Amit Kumar; Garg, Tarun; Rath, Goutam; Gupta, Umesh Datta; Gupta, Pushpa

2015-11-02

The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.

Gluten content of medications.

PubMed

Cruz, Joseph E; Cocchio, Craig; Lai, Pak Tsun; Hermes-DeSantis, Evelyn

2015-01-01

The establishment of a database for the identification of the presence of gluten in excipients of prescription medications is described. While resources are available to ascertain the gluten content of a given medication, these resources are incomplete and often do not contain a source and date of contact. The drug information service (DIS) at Robert Wood Johnson University Hospital (RWJUH) determined that directly contacting the manufacturer of a product is the best method to determine the gluten content of medications. The DIS sought to establish a resource for use within the institution and create directions for obtaining this information from manufacturers to ensure uniformity of the data collected. To determine the gluten content of a medication, the DIS analyzed the manufacturer's package insert to identify any statement indicating that the product contained gluten or inactive ingredients from known sources of gluten. If there was any question about the source of an inactive ingredient or if no information about gluten content appeared in the package insert, the manufacturer of the particular formulation of the queried medication was contacted to provide clarification. Manufacturers' responses were collected, and medications were categorized as "gluten free," "contains gluten," or "possibly contains gluten." To date, the DIS at RWJUH has received queries about 84 medications and has cataloged their gluten content. The DIS at RWJUH developed a database that categorizes the gluten status of medications, allowing clinicians to easily identify drugs that are safe for patients with celiac disease. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

A rapid micro quantification method of paracetamol in suppositories using differential scanning calorimetry.

PubMed

Noordin, Mohamed I; Chung, L Y

2004-01-01

This study adopts Differential Scanning Calorimetry (DSC) to analyze the thermal properties of samples (2.5-4.0 mg) from the tip, middle, and base sections of individual paracetamol suppositories, which were sampled carefully using a stainless steel scalpel. The contents of paracetamol present in the samples obtained from these sections were determined from the enthalpies of fusion of paracetamol and expressed as % w/w paracetamol to allow comparison of the amount of paracetamol found in each section. The tip, middle, and base sections contained 10.1+/-0.2%, 10.1+/-0.2%, and 10.3+/-0.2% w/w paracetamol, and are statistically similar (One-way anova; p>0.05). This indicates that the preparation technique adopted produces high quality suppositories in terms of content uniformity. The contents of paracetamol in the 120-mg paracetamol suppositories determined by DSC and UV spectrophotometry were statistically equivalent (Students's t-test; p>0.05), 120.8+/-2.6 mg and 120.8+/-1.5 mg, respectively, making DSC a clear alternative method for the measurement of content of drug in suppositories. The main advantages of the method are that samples of only 2.5-4.0 mg are required and the procedure does not require an extraction process, which allows for the analysis to be completed rapidly. In addition, it is highly sensitive and reproducible, with the lower detection limit at 4.0% w/w paracetamol, which is about 2.5 times lower than the content of paracetamol (10% w/w) present in our 120-mg paracetamol suppositories and commercial paracetamol suppositories, which contained about 125 mg paracetamol. Therefore, this method is particularly suited for determination of content uniformity in individual suppositories in quality control (QC) and in process quality control (PQC).

PHARMACEUTICAL QUALITY OF GENERIC ATORVASTATIN PRODUCTS COMPARED WITH THE INNOVATOR PRODUCT: A NEED FOR REVISING PRICING POLICY IN PALESTINE.

PubMed

Shawahna, Ramzi; Hroub, Abdel Kareem; Abed, Eliama; Jibali, Sondos; Al-Saghir, Ruba; Zaid, Abdel Naser

2016-01-01

Atorvastatin reduces morbidity and mortality due to cardiovascular events. This study was conducted to assess the prices and pharmaceutical quality of innovator atorvastatin 20 mg with its locally available generics in Palestine and to assess the suitability of their interchangeability. The prices of innovator and generic atorvastatin 20 mg were determined and compared. Innovator atorvastatin and four generic products were tested for their pharmaceutical quality. Tablets were tested for their drug contents, weight uniformity, hardness, disintegration and dissolution. Three out of four generics were less expensive than the innovator. Pharmaceutical quality assessments were satisfactory and within limits for all atorvastatin tested products. The average weight ranged from 206.6 ± 8.40 to 330 ± 3.92 mg and the %RSDs were within the permitted limits as per USP. Tablet hardness ranged from 102 ± 1.41 to 197.4 ± 6.88 kg and drug contents ranged from 92.2% to 105.3%. All products disintegrated within permitted time limits and showed very rapid dissolution. Products released more than 85% of their drug contents in less than 15 min. Our results showed that all tested innovator and generic atorvastatin products were of good pharmaceutical quality. Despite the lack of in vivo evaluation, our results indicate that these products are equivalent in vitro. Considering the in vitro release characteristics, these products might be used interchangeably. However, regulatory authorities permit the use of in vitro data in establishing similarity between immediate release oral dosage forms containing biopharmaceutical classification system class I and III drugs only.

Use of Bayesian Methods to Analyze and Visualize Content Uniformity Capability Versus United States Pharmacopeia and ASTM Standards.

PubMed

Hofer, Jeffrey D; Rauk, Adam P

2017-02-01

The purpose of this work was to develop a straightforward and robust approach to analyze and summarize the ability of content uniformity data to meet different criteria. A robust Bayesian statistical analysis methodology is presented which provides a concise and easily interpretable visual summary of the content uniformity analysis results. The visualization displays individual batch analysis results and shows whether there is high confidence that different content uniformity criteria could be met a high percentage of the time in the future. The 3 tests assessed are as follows: (a) United States Pharmacopeia Uniformity of Dosage Units <905>, (b) a specific ASTM E2810 Sampling Plan 1 criterion to potentially be used for routine release testing, and (c) another specific ASTM E2810 Sampling Plan 2 criterion to potentially be used for process validation. The approach shown here could readily be used to create similar result summaries for other potential criteria. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Critical material attributes (CMAs) of strip films loaded with poorly water-soluble drug nanoparticles: I. Impact of plasticizer on film properties and dissolution

PubMed Central

Krull, Scott M.; Patel, Hardik V.; Li, Meng; Bilgili, Ecevit; Davé, Rajesh N.

2016-01-01

Recent studies have demonstrated polymer films to be a promising platform for delivery of poorly water-soluble drug particles. However, the impact of critical material attributes, for example plasticizer, on the properties of and drug release from such films has yet to be investigated. In response, this study focuses on the impact of plasticizer and plasticizer concentration on properties and dissolution rate of polymer films loaded with poorly water-soluble drug nanoparticles. Glycerin, triacetin, and polyethylene glycol were selected as film plasticizers. Griseofulvin was used as a model Biopharmaceutics Classification System class II drug and hydroxypropyl methylcellulose was used as a film-forming polymer. Griseofulvin nanoparticles were prepared via wet stirred media milling in aqueous suspension. A depression in film glass transition temperature was observed with increasing plasticizer concentration, along with a decrease in film tensile strength and an increase in film elongation, as is typical of plasticizers. However, the type and amount of plasticizer necessary to produce strong yet flexible films had no significant impact on the dissolution rate of the films, suggesting that film mechanical properties can be effectively manipulated with minimal impact on drug release. Griseofulvin nanoparticles were successfully recovered upon redispersion in water regardless of plasticizer or content, even after up to 6 months’ storage at 40 °C and 75% relative humidity, which contributed to similar consistency in dissolution rate after 6 months’ storage for all films. Good content uniformity (<4% R.S.D. for very small film sample size) was also maintained across all film formulations. PMID:27402100

Montmorillonite-Alginate Composites as a Drug delivery System: Intercalation and In vitro Release of Diclofenac sodium

PubMed Central

Kevadiya, B. D.; Patel, H. A.; Joshi, G. V.; Abdi, S. H. R.; Bajaj, H. C.

2010-01-01

Diclofenac sodium and alginate was intercalated into montmorillonite to form uniform sized beads by gelation method. The structure and surface morphology of the synthesized composite beads were characterized by powdered X-ray diffraction, Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning electron microscopy. Diclofenac release kinetics of the composite in simulated intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in vitro release of diclofenac from diclofenac-montmorillonite-alginate composites bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation efficiency in the montmorillonite-alginate composites bead increases with an increase in the montmorillonite content. The control release of diclofenac from diclofenac-montmorillonite-alginate composites beads was observed to be better as compared to diclofenac-alginate beads. PMID:21969745

Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP.

PubMed

Muselík, Jan; Franc, Aleš; Doležel, Petr; Goněc, Roman; Krondlová, Anna; Lukášová, Ivana

2014-09-01

The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API) warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS) regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.

Continuous direct tablet compression: effects of impeller rotation rate, total feed rate and drug content on the tablet properties and drug release.

PubMed

Järvinen, Maiju A; Paaso, Janne; Paavola, Marko; Leiviskä, Kauko; Juuti, Mikko; Muzzio, Fernando; Järvinen, Kristiina

2013-11-01

Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages. This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process. The tablet formulations consisted of acetaminophen (3-30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69-96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8 min and steady state was reached within 5 min. The effects of acetaminophen content, impeller rotation rate (39-254 rpm) and total feed rate (15 and 20 kg/h) on tablet properties were examined. All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20 kg/h). A compression force of 12 kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8 kN. In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.

The influence of recrystallized caffeine on water-swellable polymethacrylate mucoadhesive buccal films.

PubMed

Morales, Javier O; Su, Rong; McConville, Jason T

2013-06-01

The aim of this work was to investigate the influence of particles on the properties of polymethacrylate films intended for buccal delivery. A solvent casting method was used with Eudragit RS and RL (ERS and ERL, respectively) as film-forming rate-controlling polymers, with caffeine as a water-soluble model drug. The physicochemical properties of the model films for a series of formulations with increasing concentrations of caffeine were determined in terms of morphology, mechanical and mucoadhesive properties, drug content uniformity, and drug release and associated kinetics. Typically regarded as non-mucoadhesive polymers, ERS and mainly ERL, were found to be good mucoadhesives, with ERL01 exhibiting a work of mucoadhesion (WoA) of 118.9 μJ, which was about five to six times higher than that observed for commonly used mucoadhesives such as Carbopol(®) 974P (C974P, 23.9 μJ) and polycarbophil (PCP, 17.4 μJ). The mucoadhesive force for ERL01 was found to be significantly lower yet comparable to C974P and PCP films (211.1 vs. 329.7 and 301.1 mN, respectively). Inspection of cross-sections of the films indicated that increasing the concentration of caffeine was correlated with the appearance of recrystallized agglomerates. In conclusion, caffeine agglomerates had detrimental effects in terms of mucoadhesion, mechanical properties, uniformity, and drug release at large particle sizes. ERL series of films exhibited very rapid release of caffeine while ERS series showed controlled release. Analysis of release profiles revealed that kinetics changed from a diffusion controlled to a first-order release mechanism.

Development, optimization and evaluation of curcumin loaded biodegradable crosslinked gelatin film for the effective treatment of periodontitis.

PubMed

Chauhan, Sheetal; Bansal, Monika; Khan, Gayasuddin; Yadav, Sarita K; Singh, Ashish K; Prakash, Pradyot; Mishra, Brahmeshwar

2018-07-01

Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis. Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis. The film was developed by using solvent casting technique and "Design of Experiments" approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior. Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04 ± 2.4, swelling index 138.10 ± 1.25, and folding endurance 270 ± 3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7 days. The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.

Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect

PubMed Central

Venkatesh, D. Nagasamy; Baskaran, Mahendran; Karri, Veera Venkata Satyanarayana Reddy; Mannemala, Sai Sandeep; Radhakrishna, Kollipara; Goti, Sandip

2015-01-01

Nelfinavir mesylate (NFV) is an anti-viral drug, used in the treatment of Acquired Immunodeficiency Syndrome (AIDS). Poor oral bioavailability and shorter half-life (3.5–5 h) remain a major clinical limitation of NFV leading to unpredictable drug bioavailability and frequent dosing. In this context, the objective of the present study was to formulate NFV loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which can increase the solubility and oral bioavailability along with sustained release of the drug. NFV loaded PLGA-NPs were prepared by nanoprecipitation method using PLGA and Poloxomer 407. The prepared NPs were evaluated for particle size, zeta potential, morphology, drug content, entrapment efficiency (EE) and in vitro dissolution studies. Oral bioavailability studies were carried out in New Zealand rabbits by administering developed NFV PLGA-NPs and pure drug suspension. PLGA-NPs prepared by using 1:4 ratio of drug and PLGA, with a stirring rate of 1500 rpm for 4 h. The prepared NPs were in the size of 185 ± 0.83 nm with a zeta potential of 28.7 ± 0.09 mV. The developed NPs were found to be spherical with uniform size distribution. The drug content and EE of the optimized formulation were found to be 36 ± 0.19% and 72 ± 0.47% respectively. After oral administration of NFV PLGA-NPs, the relative bioavailability was enhanced about 4.94 fold compared to NFV suspension as a control. The results describe an effective strategy for oral delivery of NFV loaded PLGA NPs that helps in enhancing bioavailability and reduce the frequency of dosing. PMID:26702262

Bilayered Films Based on Novel Polymer Derivative for Improved Ocular Therapy of Gatifloxacin

PubMed Central

Aher, Naval Dinesh; Nair, Hema Ajit

2014-01-01

Context. Thiomers could prove to be suitable mucoadhesives for fabrication of ocular inserts. Objective. The study intends to explore the application of thiolated sodium alginate (TSA) to the preparation of bilayered ocular inserts of gatifloxacin. Methods. Cysteine moieties were grafted onto sodium alginate (SA) and the resultant thiomer was characterized for relevant physicochemical properties. Bilayered inserts were fabricated with a mucoadhesive immediate release layer composed of either SA or TSA and a sustained release layer composed of acrylates. Films were prepared by solvent evaporation and evaluated for mechanical properties, drug content, and in vitro release. Results and Discussion. The synthesized TSA possessed 248.80 ± 49.7 μmol thiol groups/gm and its solutions thickened on standing due to disulphide bridging. Its films showed improved mucoadhesion and also a strikingly beneficial property of resisting erosion and remaining as a hydrated adhesive layer for the duration of drug release. The bilayered films were found to be flexible, with good folding endurance, uniform thickness, and appropriate drug content, and showed a release of about 80% of loaded gatifloxacin in 12 h. Conclusion. The study demonstrates promise in employing thiolated polymer in conjunction with acrylates for the design of ocular inserts for twice a day therapy with gatifloxacin. PMID:24516362

Design and Evaluation of Microemulsion Gel System of Nadifloxacin

PubMed Central

Shinde, Ujwala; Pokharkar, Sharda; Modani, Sheela

2012-01-01

Topical microemulsion systems for the antiacne agent, nadifloxacin were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of nadifloxacin in oils, surfactants and cosurfactants was evaluated to screen the components of the microemulsion. Various surfactants and cosurfactants were screened for their ability to emulsify the selected oily phase. The pseudoternary diagrams were constructed to identify the area of microemulsion existence. The influence of km (surfactant/cosurfactant) ratio on the microemulsion existence region was determined and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterised for optical birefringence, pH and refractive index, robustness to dilution, globule size, drug content and thermodynamic stability. Optimised microemulsion systems were formulated into gel form and evaluated for viscosity, spreadability, drug content, ex vivo skin permeation and antibacterial activity. The maximum solubility of nadifloxacin in the microemulsion system was found to be 0.25%. The nadifloxacin microemulsions had a small and uniform globule size (67.3-121.23 nm). The stability results revealed that all formulations showed a stable globule size and the polydispersity index under stress conditions. Incorporation of nadifloxacin in microemulsion gel increased the ex vivo skin permeation and antibacterial activity when compared to marketed cream. PMID:23439454

Injectable, degradable, electroactive nanocomposite hydrogels containing conductive polymer nanoparticles for biomedical applications

PubMed Central

Wang, Qinmei; Wang, Qiong; Teng, Wei

2016-01-01

Injectable electroactive hydrogels (eGels) are promising in regenerative medicine and drug delivery, however, it is still a challenge to obtain such hydrogels simultaneously possessing other properties including uniform structure, degradability, robustness, and biocompatibility. An emerging strategy to endow hydrogels with desirable properties is to incorporate functional nanoparticles in their network. Herein, we report the synthesis and characterization of an injectable hydrogel based on oxidized alginate (OA) crosslinking gelatin reinforced by electroactive tetraaniline-graft-OA nanoparticles (nEOAs), where nEOAs are expected to impart electroactivity besides reinforcement without significantly degrading the other properties of hydrogels. Assays of transmission electron microscopy, 1H nuclear magnetic resonance, and dynamic light scattering reveal that EOA can spontaneously and quickly self-assemble into robust nanoparticles in water, and this nanoparticle structure can be kept at pH 3~9. Measurement of the gel time by rheometer and the stir bar method confirms the formation of the eGels, and their gel time is dependent on the weight content of nEOAs. As expected, adding nEOAs to hydrogels does not cause the phase separation (scanning electron microscopy observation), but it improves mechanical strength up to ~8 kPa and conductivity up to ~10−6 S/cm in our studied range. Incubating eGels in phosphate-buffered saline leads to their further swelling with an increase of water content <6% and gradual degradation. When growing mesenchymal stem cells on eGels with nEOA content ≤14%, the growth curves and morphology of cells were found to be similar to that on tissue culture plastic; when implanting these eGels on a chick chorioallantoic membrane for 1 week, mild inflammation response appeared without any other structural changes, indicating their good in vitro and in vivo biocompatibility. With injectability, uniformity, degradability, electroactivity, relative robustness, and biocompatibility, these eGels may have a huge potential as scaffolds for tissue regeneration and matrix for stimuli responsive drug release. PMID:26792990

Layered growth with bottom-spray granulation for spray deposition of drug.

PubMed

Er, Dawn Z L; Liew, Celine V; Heng, Paul W S

2009-07-30

The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.

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.

Transmission near-infrared (NIR) and photon time-of-flight (PTOF) spectroscopy in a comparative analysis of pharmaceuticals.

PubMed

Kamran, Faisal; Abildgaard, Otto H A; Sparén, Anders; Svensson, Olof; Johansson, Jonas; Andersson-Engels, Stefan; Andersen, Peter E; Khoptyar, Dmitry

2015-03-01

We present a comprehensive study of the application of photon time-of-flight spectroscopy (PTOFS) in the wavelength range 1050-1350 nm as a spectroscopic technique for the evaluation of the chemical composition and structural properties of pharmaceutical tablets. PTOFS is compared to transmission near-infrared spectroscopy (NIRS). In contrast to transmission NIRS, PTOFS is capable of directly and independently determining the absorption and reduced scattering coefficients of the medium. Chemometric models were built on the evaluated absorption spectra for predicting tablet drug concentration. Results are compared to corresponding predictions built on transmission NIRS measurements. The predictive ability of PTOFS and transmission NIRS is comparable when models are based on uniformly distributed tablet sets. For non-uniform distribution of tablets based on particle sizes, the prediction ability of PTOFS is better than that of transmission NIRS. Analysis of reduced scattering spectra shows that PTOFS is able to characterize tablet microstructure and manufacturing process parameters. In contrast to the chemometric pseudo-variables provided by transmission NIRS, PTOFS provides physically meaningful quantities such as scattering strength and slope of particle size. The ability of PTOFS to quantify the reduced scattering spectra, together with its robustness in predicting drug content, makes it suitable for such evaluations in the pharmaceutical industry.

Critical material attributes (CMAs) of strip films loaded with poorly water-soluble drug nanoparticles: I. Impact of plasticizer on film properties and dissolution.

PubMed

Krull, Scott M; Patel, Hardik V; Li, Meng; Bilgili, Ecevit; Davé, Rajesh N

2016-09-20

Recent studies have demonstrated polymer films to be a promising platform for delivery of poorly water-soluble drug particles. However, the impact of critical material attributes, for example plasticizer, on the properties of and drug release from such films has yet to be investigated. In response, this study focuses on the impact of plasticizer and plasticizer concentration on properties and dissolution rate of polymer films loaded with poorly water-soluble drug nanoparticles. Glycerin, triacetin, and polyethylene glycol were selected as film plasticizers. Griseofulvin was used as a model Biopharmaceutics Classification System class II drug and hydroxypropyl methylcellulose was used as a film-forming polymer. Griseofulvin nanoparticles were prepared via wet stirred media milling in aqueous suspension. A depression in film glass transition temperature was observed with increasing plasticizer concentration, along with a decrease in film tensile strength and an increase in film elongation, as is typical of plasticizers. However, the type and amount of plasticizer necessary to produce strong yet flexible films had no significant impact on the dissolution rate of the films, suggesting that film mechanical properties can be effectively manipulated with minimal impact on drug release. Griseofulvin nanoparticles were successfully recovered upon redispersion in water regardless of plasticizer or content, even after up to 6months' storage at 40°C and 75% relative humidity, which contributed to similar consistency in dissolution rate after 6months' storage for all films. Good content uniformity (<4% R.S.D. for very small film sample size) was also maintained across all film formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a fast dissolving film of epinephrine hydrochloride as a potential anaphylactic treatment for pediatrics.

PubMed

Alayoubi, Alaadin; Haynes, Lindsay; Patil, Hemlata; Daihom, Baher; Helms, Richard; Almoazen, Hassan

2017-12-01

To develop a fast dissolving film strip containing epinephrine HCl for the potential treatment of pediatric anaphylaxis. Four different films have been prepared by solvent casting technique where the percentages of the polymer (Lycoat RS720) were optimized. The polymer percentages were (20%, 25%, 27% and 30%) of the total formulation weighs. The thickness and elastic modulus of the optimized film was evaluated using dynamic mechanical analyzer. Epinephrine content uniformity was assessed using UV at wavelength 280 nm. For the dissolution test, fast dissolving films (FDFs) were evaluated in 500 Simulated Saliva, with 50 rpm. In vivo taste and disintegration evaluation was performed on six healthy volunteers. Films formed by formulations 1, 2 and 3 were too sticky after drying, while formulation 4 that has 30% polymer content formed smooth, transparent, flexible and uniform film, and therefore, it was selected for further testing. The value of elastic modulus was determined at 1.325 MPa. The thickness of the film at different locations was measured at 0.29 mm. Drug content in film was measured at 93% ±10. More than 90% of epinephrine was released from the film within 7.2 min. Bitterness of epinephrine was masked efficiently according to volunteer's comments with average disintegration time of 20 s. This study presents potential proof for using FDFs as a replacement therapy of epinephrine injections for pediatrics.

Formulation, development and characterization of mucoadhesive film for treatment of vaginal candidiasis.

PubMed

Mishra, Renuka; Joshi, Priyanka; Mehta, Tejal

2016-01-01

The objective of the present investigation was formulation, optimization and characterization of mucoadhesive film of clotrimazole (CT) which is patient-convenient and provides an effective alternative for the treatment of vaginal candidiasis. CT is an antimycotic drug applied locally for the treatment of vaginal candidiasis. Mucoadhesive vaginal films were prepared by solvent casting technique using hydroxyl propylcellulose and sodium alginate as polymers. Propylene glycol and polyethylene glycol-400 were evaluated as plasticizers. The mucoadhesive vaginal films were evaluated for percentage elongation, tensile strength, folding endurance, drug content, in vitro disintegration time, in vitro dissolution study, swelling index, bioadhesive strength, and diffusion study. Among various permeation enhancers used, isopropyl myristate was found to be suitable. To evaluate the role of the concentration of permeation enhancer and concentration of polymers in the optimization of mucoadhesive vaginal film, 3(2) full factorial design was employed. Optimized batch showed in vitro disintegration time, 18 min; drug content, 99.83%; and tensile strength, 502.1 g/mm(2). In vitro diffusion study showed that 77% drug diffusion occurred in 6 h. This batch was further evaluated by scanning electron microscopy indicating uniformity of the film. In vitro Lactobacillus inhibition and in vitro antifungal activity of optimized batch showed an inhibitory effect against Candida albicans and no effect on Lactobacillus, which is a normal component of vaginal flora. Mucoadhesive vaginal film of CT is an effective dosage form for the treatment of vaginal candidiasis.

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.

Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form

PubMed Central

Khale, Anubha; Bajaj, Amrita

2011-01-01

In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation. PMID:22923867

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

PubMed

Al-Hanbali, Othman A; Hamed, Rania; Arafat, Mosab; Bakkour, Youssef; Al-Matubsi, Hisham; Mansour, Randa; Al-Bataineh, Yazan; Aldhoun, Mohammad; Sarfraz, Muhammad; Dardas, Abdel Khaleq Yousef

2018-01-01

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

3D Printed "Starmix" Drug Loaded Dosage Forms for Paediatric Applications.

PubMed

Scoutaris, Nicolaos; Ross, Steven A; Douroumis, Dennis

2018-01-16

Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print "candy - like" formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability. Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug - excipient interactions and the content uniformity. Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min. 3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.

Thermal protective uniforms and hoods: impact of design modifications and water content on burn prevention in New York City firefighters: laboratory and field results

PubMed Central

Prezant, D; Malley, K; Barker, R; Guerth, C; Kelly, K

2001-01-01

Objectives—To determine (1) the effectiveness of hoods in reducing head burns, (2) the impact of clothes worn under the protective outer uniform (modern = long sleeve shirt and long pants; modified modern = short sleeve T-shirt and short pants) on burns, and (3) whether water content (dry, damp or saturated) affects the level of thermal protection. Setting—Fire Department of the City of New York (FDNY). Methods—Laboratory tests (fully dressed manikin) evaluated the different uniform and water conditions when exposed to an average 24 cal/cm2 heat flux, approximately 2250°F air temperature. FDNY field results compared (1) head burns during winters wearing the hood to winters without hood and (2) upper and lower extremity burns during summers wearing traditional, modern, and modified modern uniforms. Results—Laboratory tests showed that thermal protection was: (1) dramatically improved by the hood with protection increasing as water content increased and (2) not significantly different between modern and modified modern uniforms, regardless of water content. FDNY field results confirmed these tests showing (1) significant decreases in neck burns (by 54%), ear burns (by 60%), and head burn totals (by 46%) wearing the hood and (2) no significant differences in upper or lower extremity burns wearing modern compared with modified modern uniforms. Conclusions—Based on combined laboratory and field results, we strongly recommend the use of modern thermal protective hoods and the modified modern uniform. PMID:11565971

Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century.

PubMed

Tiwari, Roshan V; Patil, Hemlata; Repka, Michael A

2016-01-01

Hot-melt extrusion (HME) technology is applied successfully in the plastic, rubber and food industry. HME has also emerged as an important technology for drug delivery applications in pharmaceutical research and manufacturing because of its process automation and low-cost scale-up properties, which reduce labor costs and capital investment. There are a number of commercial FDA-approved HME-derived products, signifying the commercial feasibility of this novel technique in drug delivery applications. HME is a highly efficient, solvent-free continuous processing technique for the development of solid dispersions; thus, research efforts to develop sustained, modified and targeted drug delivery systems to improve the solubility and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) are of interest. This review focuses on both the innovations and applications of HME in the production of pharmaceutical formulations, and on the significant findings of the general principles regarding formulation and process development via HME as described in published articles. Challenges faced by pharmaceutical companies to produce efficient drug formulations may be partly overcome by HME's advantages - high drug-loading capacity, good content uniformity, cost-effectiveness, and ease of processing scale-up. Nevertheless, HME's high processing temperatures may be an obstacle if adequate knowledge about the product's formulation is lacking.

Design and Optimization of Floating Drug Delivery System of Acyclovir

PubMed Central

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Design and optimization of floating drug delivery system of acyclovir.

PubMed

Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

2010-09-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

Male enhancement Nutraceuticals in the Middle East market: Claim, pharmaceutical quality and safety assessments.

PubMed

ElAgouri, Ghada; ElAmrawy, Fatema; ElYazbi, Ahmed; Eshra, Ahmed; Nounou, Mohamed I

2015-08-15

The global market is invaded by male enhancement nutraceuticals claimed to be of natural origin sold with a major therapeutic claim. Most of these products have been reported by international systems like the Food and Drug Administration (FDA). We hypothesize that these products could represent a major threat to the health of the consumers. In this paper, pharmaceutical evaluation of some of these nutraceutical products sold in Egypt under the therapeutic claim of treating erectile dysfunction, are discussed along with pharmacological evaluation to investigate their safety and efficacy parameters. Samples were analyzed utterly using conventional methods, i.e.: HPLC, HPTLC, NIR, content uniformity and weight variation and friability. The SeDeM system was used for quality assessment. On the basis of the results of this research, the sampled products are adulterated and totally heterogeneous in their adulterant drug content and pharmaceutical quality. These products represent a major safety threat for the consumers in Egypt and the Middle East, especially; the target audience is mostly affected with heart and blood pressure problems seeking natural and safe alternatives to the well-established Phosphodiesterase 5 Inhibitors (PDE-5Is). Copyright © 2015 Elsevier B.V. All rights reserved.

Host-guest interaction induced supramolecular amphiphilic star architecture and uniform nanovesicle formation for anticancer drug delivery

NASA Astrophysics Data System (ADS)

Zhu, Jing-Ling; Liu, Kerh Li; Wen, Yuting; Song, Xia; Li, Jun

2016-01-01

A star polymer of poly[(R,S)-3-hydroxybutyrate] (PHB) with adamantyl end-terminals extended from an α-cyclodextrin (α-CD) core is designed. It subsequently self-assembles to form controllable and uniform nanovesicles induced by host-guest interactions between heptakis(2,6-di-O-methyl)-β-CD and the adamantyl ends. The nanovesicles are suitable for loading and intracellular delivery of the anticancer drug doxorubicin.A star polymer of poly[(R,S)-3-hydroxybutyrate] (PHB) with adamantyl end-terminals extended from an α-cyclodextrin (α-CD) core is designed. It subsequently self-assembles to form controllable and uniform nanovesicles induced by host-guest interactions between heptakis(2,6-di-O-methyl)-β-CD and the adamantyl ends. The nanovesicles are suitable for loading and intracellular delivery of the anticancer drug doxorubicin. Electronic supplementary information (ESI) available: Polymer synthesis, characterization, preparation of drug-loaded nanovesicles, intracellular drug release and cytotoxicity assays, TEM and DLS measurements. See DOI: 10.1039/c5nr06744h

7 CFR 51.891 - Uniform in appearance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Vinifera Type) 1 Definitions § 51.891 Uniform in appearance. Uniform in appearance means that not more than... materially detract from the appearance of the contents of the individual container, and that the stems are...

7 CFR 51.891 - Uniform in appearance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Vinifera Type) 1 Definitions § 51.891 Uniform in appearance. Uniform in appearance means that not more than... materially detract from the appearance of the contents of the individual container, and that the stems are...

Uniform Sampling Table Method and its Applications II--Evaluating the Uniform Sampling by Experiment.

PubMed

Chen, Yibin; Chen, Jiaxi; Chen, Xuan; Wang, Min; Wang, Wei

2015-01-01

A new method of uniform sampling is evaluated in this paper. The items and indexes were adopted to evaluate the rationality of the uniform sampling. The evaluation items included convenience of operation, uniformity of sampling site distribution, and accuracy and precision of measured results. The evaluation indexes included operational complexity, occupation rate of sampling site in a row and column, relative accuracy of pill weight, and relative deviation of pill weight. They were obtained from three kinds of drugs with different shape and size by four kinds of sampling methods. Gray correlation analysis was adopted to make the comprehensive evaluation by comparing it with the standard method. The experimental results showed that the convenience of uniform sampling method was 1 (100%), odds ratio of occupation rate in a row and column was infinity, relative accuracy was 99.50-99.89%, reproducibility RSD was 0.45-0.89%, and weighted incidence degree exceeded the standard method. Hence, the uniform sampling method was easy to operate, and the selected samples were distributed uniformly. The experimental results demonstrated that the uniform sampling method has good accuracy and reproducibility, which can be put into use in drugs analysis.

Formulation and evaluation of buccal film of Ivabradine hydrochloride for the treatment of stable angina pectoris

PubMed Central

Lodhi, Mohasin; Dubey, Akhilesh; Narayan, Reema; Prabhu, Prabhakara; Priya, Sneh

2013-01-01

Background: Ivabradine hydrochloride is an anti-anginal drug with a biological half-life of about 2 h, and repeated daily administration is needed to maintain effective plasma level. Present investigation of buccal films of Ivabradine hydrochloride is an attempt to avoid the repeated administration and release of drug in more controlled fashion, thereby, to improve the bioavailability. Materials and Methods: Buccal patches were fabricated by solvent casting technique and were evaluated for its physical properties like physical appearance, weight uniformity, thickness, swelling index, surface pH, mucoadhesive time, and folding endurance, in vitro and ex vivo release studies. Results: A combination of hydroxypropyl methyl cellulose (HPMC) K15M and K100M with carbopol 940, PEG 6000 gave promising results. Further, the drug content of all the formulations was determined and was found to be uniform. All the formulations were subjected to in vitro release study using phosphate buffer pH 6.6. Patches exhibited drug release in the range of 90.36% ± 0.854 to 98.37% ± 0.589 at the end of six hrs. The best formulations (F2 and F5) containing the composition of HPMC K15-37.50 mg, carbopol-0.42 mg, PEG6000-16.87 mg, Aspertane-0.28 mg, Tween-0.0023 mg and HPMC K100-37.50 mg, carbopol-0.42 mg, PEG6000-16.87 mg, Aspertane-0.28 mg, Tween-0.0023 mg respectively exhibited in vitro drug release of 97.61% ± 0.589 and 98.37% ± 0.114 respectively. The results of ex vivo diffusion using goat cheek pouch revealed that the drug release rate was retarded up to seven hrs. Films prepared with permeation enhancer (Tween 80) showed faster drug release. Finally, stability studies were carried out by using human saliva for the optimized formulation (F2-F5). Conclusion: The present study indicated enormous potential of mucoadhesive buccal patches containing Ivabradine for systemic delivery with an added advantage of circumventing hepatic first pass metabolism. Further work is recommended to support its efficacy claims by long term pharmacokinetic and pharmacodynamic studies in human beings. PMID:23799205

In vitro studies on guar gum based formulation for the colon targeted delivery of Sennosides.

PubMed

Momin, Munira; Pundarikakshudu, K

2004-09-24

The objective of the present study is to develop colon targeted drug delivery systems for sennosides using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for content uniformity and in vitro drug release study as per BP method. T(50) % value from the dissolution studies was taken for selecting the best formulation. Guar gum matrix tablets released 4-18% sennosides in the physiological environment of gastrointestinal tract depending on the proportion of the guar gum used in the formulation. The matrix tablets containing 50% of guar gum were found to be suitable for targeting of sennosides for local action in the colon. Compared to tablets having 30% and 40% of guar gum, those with 50% guar gum gave better T(50)% (11.7 h) le and fewer amounts (5-8%) of drug release in upper GIT. These tablets with 50% guar gum released 43% and 96% sennosides with and without rat caecal fluids. This suggests the susceptibility of matrix to the colonic micro flora. The similarity factor (f2 value) for drug release with and without rat caecal fluids was found to be less than 30. When hydroxy propyl methylcellulose phthalate (10%) was used as a coat material on the matrix tablets, the initial loss of 5-8% sennosides in stomach could be completely averted. These tablets showed no change in physical appearance, content and dissolution profile upon storage at 45 degrees C / 75% relative humidity for 3 months. The results of our study indicates that matrix tablets containing 50% guar gum and coated with 10% hydroxy propyl methylcellulose phthalate are most suitable for drugs like sennosides which are mainly active in the lower GIT.

[Breeding of new varieties "zhongchai no. 2" and "zhongchai no. 3" of Bupleurum chinense].

PubMed

Zheng, Tingting; Sui, Chun; Wei, Jianhe; Jin, Yue; Chu, Qinglong; Yang, Chengmin

2010-08-01

To breed new varieties with better uniformity and commercial quality as well as higher saikosaponin contents. The excellent germplasm resources were selected from "zhongchai no. 1" population. Single plant method was applied to get better varieties. All the breeding material was investigated according to morphological characters, agronomic characters and the contents of saikosaponin a and saikosaponin d. The experiments of comparative test and varieties regional test were carried out. The bred new varieties of "zhongchai No. 2" and "zhongchai No. 3" had better uniformity. The dark brown roots ratios of the two varieties were 83.2%, 89.9%, respectively. The contents of saikosaponins (a + d) of the two varieties reached 1.31%, 1.02%, respectively. "zhongchai No. 2" and " zhongchai No. 3" both had the advantages of better uniformity, darker brown roots and higher saikosaponin contents.

Formulation characteristics and in vitro release testing of cyclosporine ophthalmic ointments.

PubMed

Dong, Yixuan; Qu, Haiou; Pavurala, Naresh; Wang, Jiang; Sekar, Vasanthakumar; Martinez, Marilyn N; Fahmy, Raafat; Ashraf, Muhammad; Cruz, Celia N; Xu, Xiaoming

2018-06-10

The aim of the present study was to investigate the relationship between formulation/process variables versus the critical quality attributes (CQAs) of cyclosporine ophthalmic ointments and to explore the feasibility of using an in vitro approach to assess product sameness. A definitive screening design (DSD) was used to evaluate the impact of formulation and process variables. The formulation variables included drug percentage, percentage of corn oil and lanolin alcohol. The process variables studied were mixing temperature, mixing time and the method of mixing. The quality and performance attributes examined included drug assay, content uniformity, image analysis, rheology (storage modulus, shear viscosity) and in vitro drug release. Of the formulation variables evaluated, the percentage of the drug substance and the percentage of corn oil in the matrix were the most influential factors with respect to in vitro drug release. Conversely, the process parameters tested were observed to have minimal impact. An evaluation of the release mechanism of cyclosporine from the ointment revealed an interplay between formulation (e.g. physicochemical properties of the drug and ointment matrix type) and the release medium. These data provide a scientific basis to guide method development for in vitro drug release testing of ointment dosage forms. These results demonstrate that the in vitro methods used in this investigation were fit-for-purpose for detecting formulation and process changes and therefore amenable to assessment of product sameness. Published by Elsevier B.V.

Formulation and process factors influencing product quality and in vitro performance of ophthalmic ointments.

PubMed

Xu, Xiaoming; Al-Ghabeish, Manar; Rahman, Ziyaur; Krishnaiah, Yellela S R; Yerlikaya, Firat; Yang, Yang; Manda, Prashanth; Hunt, Robert L; Khan, Mansoor A

2015-09-30

Owing to its unique anatomical and physiological functions, ocular surface presents special challenges for both design and performance evaluation of the ophthalmic ointment drug products formulated with a variety of bases. The current investigation was carried out to understand and identify the appropriate in vitro methods suitable for quality and performance evaluation of ophthalmic ointment, and to study the effect of formulation and process variables on its critical quality attributes (CQA). The evaluated critical formulation variables include API initial size, drug percentage, and mineral oil percentage while the critical process parameters include mixing rate, temperature, time and cooling rate. The investigated quality and performance attributes include drug assay, content uniformity, API particle size in ointment, rheological characteristics, in vitro drug release and in vitro transcorneal drug permeation. Using design of experiments (DoE) as well as a novel principle component analysis approach, five of the quality and performance attributes (API particle size, storage modulus of ointment, high shear viscosity of ointment, in vitro drug release constant and in vitro transcorneal drug permeation rate constant) were found to be highly influenced by the formulation, in particular the strength of API, and to a lesser degree by processing variables. Correlating the ocular physiology with the physicochemical characteristics of acyclovir ophthalmic ointment suggested that in vitro quality metrics could be a valuable predictor of its in vivo performance. Published by Elsevier B.V.

Content Analysis of Measures for Identification of Elder Abuse.

ERIC Educational Resources Information Center

Sengstock, Mary C.; And Others

Measures designed to detect elder abuse lack uniformity as a result of having been designed in isolation. To develop and test a uniform index for the identification of elder abuse victims, an analysis of existing abuse identification instruments was conducted. Initially, seven elder abuse identification measures were content analyzed, resulting in…

Formulation development and comparative in vitro study of metoprolol tartrate (IR) tablets.

PubMed

Husain, Tazeen; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Maboos, Madiha; Khan, Madeeha; Bashir, Lubna; Naz, Shazia

2016-05-01

The objective of the present work was to develop Immediate Release (IR) tablets of Metoprolol Tartrate (MT) and to compare trial formulations to a reference product. Six formulations (F1-F6) were designed using central composite method and compared to a reference brand (A). Two marketed products (brands B and C) were also evaluated. F1-F6 were prepared with Avicel PH101 (filler), Crospovidone (disintegrant) and Magnesium Stearate (lubricant) by direct compression. Pharmacopoeial and non-pharmacopoeial methods were used to assess their quality. Furthermore, drug profiles were characterized using model dependent and independent (f(2)) approaches. Brands B and C and F5 and F6 did not qualify the tests for content uniformity. Moreover, brand B did not meet weight variation criteria and brand C did not satisfy requirements for single point dissolution test. Of the trial formulations, F2 failed the test for uniformity in thickness while F4 did not disintegrate within time limit. Only F1 and F3 met all quality parameters and were subjected to accelerated stability testing without significant alterations in their physicochemical characteristics. Based on AIC and r(2)(adjusted) values obtained by applying various kinetic models, drug release was determined to most closely follow Hixson-Crowell cube root law. F1 was determined to be the optimized formulation.

Formulation and in vitro evaluation of xanthan gum or carbopol 934-based mucoadhesive patches, loaded with nicotine.

PubMed

Abu-Huwaij, Rana; Obaidat, Rana M; Sweidan, Kamal; Al-Hiari, Yusuf

2011-03-01

Bilayer nicotine mucoadhesive patches were prepared and evaluated to determine the feasibility of the formulation as a nicotine replacement product to aid in smoking cessation. Nicotine patches were prepared using xanthan gum or carbopol 934 as a mucoadhesive polymers and ethyl cellulose as a backing layer. The patches were evaluated for their thickness, weight and content uniformity, swelling behavior, drug-polymers interaction, adhesive properties, and drug release. The physicochemical interactions between nicotine and the polymers were investigated by Fourier transform infrared (FTIR) spectroscopy. Mucoadhesion was assessed using two-arm balance method, and the in vitro release was studied using the Franz cell. FTIR revealed that there was an acid base interaction between nicotine and carbopol as well as nicotine and xanthan. Interestingly, the mucoadhesion and in vitro release studies indicated that this interaction was strong between the drug and carbopol whereas it was weak between the drug and xanthan. Loading nicotine concentration to non-medicated patches showed a significant decrease in the mucoadhesion strength of carbopol patches and no significant effect on the mucoadhesion strength of xanthan patches. In vitro release studies of the xanthan patches showed a reasonable fast initial release profile followed by controlled drug release over a 10-h period. © 2010 American Association of Pharmaceutical Scientists

Lornoxicam gastro retentive floating matrix tablets: Design and in vitro evaluation.

PubMed

Sathiyaraj, S; Devi, Ramya D; Hari, Vedha B N

2011-07-01

The objective of this present investigation is to prolong the gastric residence time of Lornoxicam by fabricating it into a floating sustained release matrix tablets. Lornoxicam, a potent oxicam group of non-steroidal anti-inflammatory drugs, suffers from relatively short half life of 2 to 3 hrs showing maximal absorption in proximal gastro intestinal tract region necessitating its need to be formulated as a floating sustained release matrix tablets. In this current investigation, hydroxyl propyl methyl cellulose K15M, a high viscous grade polymer with apparent viscosity of 15,000 cps, was kept as a variable (10-50%) and calcium carbonate (13%) was used as a gas generator. The prepared blends were subjected for its pre-formulation characterization. The directly compressed tablets were evaluated for physical parameters such as weight uniformity, hardness, friability, drug content, in-vitro buoyancy with axial and radial enlargement measurement, swelling index. From the investigation it was observed that the buoyancy lasted for up to 24 hrs. Fourier transform infra-red spectroscopy peaks assured the compatibility of the drug with excipients and confirmed the presence of pure drug in the formulation. It was supported by in-vitro dissolution studies; and the dissolution data was subjected to various release kinetic models to understand the mechanism of drug release.

Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy.

PubMed

Okeke, Obinna C; Boateng, Joshua S

2016-10-01

Smoking cessation is of current topical interest due to the significant negative health and economic impact in many countries. This study aimed to develop buccal films and wafers comprising HPMC and sodium alginate (SA) for potential use in nicotine replacement therapy via the buccal mucosa, as a cheap but effective alternative to currently used nicotine patch and chewing gum. The formulations were characterised using texture analyser (tensile and hardness, mucoadhesion), scanning electron microscopy, X-ray diffractometry, attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC) and swelling capacity. Drug loaded films and wafers were characterised for content uniformity (HPLC) whilst the drug loaded wafers only were further characterised for in vitro drug dissolution. SA modified and improved the functional properties of HPMC at optimum ratio of HPMC: SA of 1.25: 0.75. Generally, both films and wafers (blank and drug loaded) were amorphous in nature which impacted on swelling and mucoadhesive performance. HPMC-SA composite wafers showed a porous internal morphology with higher mucoadhesion, swelling index and drug loading capacity compared to the HPMC-SA composite films which were non-porous. The study demonstrates the potential use of composite HPMC-SA wafers in the buccal delivery nicotine. Copyright © 2016 Elsevier B.V. All rights reserved.

A new definition of pharmaceutical quality: assembly of a risk simulation platform to investigate the impact of manufacturing/product variability on clinical performance.

PubMed

Short, Steven M; Cogdill, Robert P; D'Amico, Frank; Drennen, James K; Anderson, Carl A

2010-12-01

The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to "modernize" the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Qualitative and Quantitative Assessment of Four Marketed Formulations of Brahmi

PubMed Central

Saini, Neeti; Mathur, Rajani; Agrawal, S. S.

2012-01-01

This study was conducted with the aim to compare two batches each of four popular commercial formulations of Bacopa monnieri (Brahmi), and report, if any, inter-batch variations. The formulations were procured from local market and analyzed for label specifications, uniformity of weight of capsule, identity, purity and strength parameters (total ash content test, acid insoluble ash content, water soluble extractive, alcohol soluble extractive, loss on drying). Bacoside A, one of the pharmacologically active saponin present in B. monnieri, was quantified in all the formulations using UV-spectrophotometer. In addition each formulation was assessed and compared for variation in biological activity using in vitro test for hemolytic activity using human erythrocytes. The results of the study show that there is a wide variation in the quality and content of herbal drugs marketed by different manufacturers. More importantly this study demonstrates that there exists a bigger challenge of batch-to-batch variation in the quality and content of herbal formulations of the same manufacturer. This challenge of providing standardized formulations is being faced by not any one manufacturing house but by all, and may be attributed firstly to, lack of stringent regulations and secondly to high variability in raw material quality. PMID:23204618

Qualitative and quantitative assessment of four marketed formulations of brahmi.

PubMed

Saini, Neeti; Mathur, Rajani; Agrawal, S S

2012-01-01

This study was conducted with the aim to compare two batches each of four popular commercial formulations of Bacopa monnieri (Brahmi), and report, if any, inter-batch variations. The formulations were procured from local market and analyzed for label specifications, uniformity of weight of capsule, identity, purity and strength parameters (total ash content test, acid insoluble ash content, water soluble extractive, alcohol soluble extractive, loss on drying). Bacoside A, one of the pharmacologically active saponin present in B. monnieri, was quantified in all the formulations using UV-spectrophotometer. In addition each formulation was assessed and compared for variation in biological activity using in vitro test for hemolytic activity using human erythrocytes. The results of the study show that there is a wide variation in the quality and content of herbal drugs marketed by different manufacturers. More importantly this study demonstrates that there exists a bigger challenge of batch-to-batch variation in the quality and content of herbal formulations of the same manufacturer. This challenge of providing standardized formulations is being faced by not any one manufacturing house but by all, and may be attributed firstly to, lack of stringent regulations and secondly to high variability in raw material quality.

Oil from pumpkin (Cucurbita pepo L.) seeds: evaluation of its functional properties on wound healing in rats.

PubMed

Bardaa, Sana; Ben Halima, Nihed; Aloui, Fatma; Ben Mansour, Riadh; Jabeur, Hazem; Bouaziz, Mohamed; Sahnoun, Zouheir

2016-04-11

Increasing natural drug demand for pharmaceutical uses has encouraged scientifics all over the world to explore medicinal plants recognized as efficient remedies. In this context, extracted oil from pumpkin seeds (Cucurbita pepo L.) is an interesting target, as it is composed with prominent pharmacological properties to possible wound healing treatments. The composition and content of certain bioactive constituents of the cold pressed oil obtained from pumpkin seeds (Cucurbita pepo L.) were analyzed and studied for their wound healing properties. Uniform wounds were induced on the dorsum of 18 rats, randomly divided into three groups. The wounds were photographed, and topically treated with saline solution (control group), 0.13 mg/mm(2) of a reference drug ("Cicaflora cream®"), and 0.52 μl/mm(2) of pumpkin's oil each 2 days until the first group is completely healing and so far biopsies were histologically assessed. The composition and content of tocopherols, fatty acids, and phytosterols were determined. The results showed an excellent quality of pumpkin oil with high content of polyunsaturated fatty acids (Linoleic acid: 50.88 ± 0.106 g/100 g of total fatty acids), tocopherols (280 ppm) and sterols (2086.5 ± 19.092 ppm). High content of these bioactive components were in agreement with an efficient wound healing by the mean of an in vivo study. In fact, morphometric assessment and histological findings revealed healed biopsies from pumpkin oil treated group of rats, unlike untreated group, and a full re-epithelialization with reappearance of skin appendages and well organized collagen fibers without inflammatory cells. This study showed the significance of oil from pumpkin seeds (Cucurbita pepo L.) as a promising drug to healing wounds in animal assays. As a whole, pumpkin's oil would be recommended in the nutritional and medicinal purposes.

The DOI Is Coming.

ERIC Educational Resources Information Center

Scharf, Davida

2002-01-01

Discussion of improving accessibility to copyrighted electronic content focuses on the Digital Object Identifier (DOI) and the Open URL standard and linking software. Highlights include work of the World Wide Web consortium; URI (Uniform Resource Identifier); URL (Uniform Resource Locator); URN (Uniform Resource Name); OCLC's (Online Computer…

The Production of 3D Tumor Spheroids for Cancer Drug Discovery

PubMed Central

Sant, Shilpa; Johnston, Paul A.

2017-01-01

New cancer drug approval rates are ≤ 5% despite significant investments in cancer research, drug discovery and development. One strategy to improve the rate of success of new cancer drugs transitioning into the clinic would be to more closely align the cellular models used in the early lead discovery with pre-clinical animal models and patient tumors. For solid tumors, this would mandate the development and implementation of three dimensional (3D) in vitro tumor models that more accurately recapitulate human solid tumor architecture and biology. Recent advances in tissue engineering and regenerative medicine have provided new techniques for 3D spheroid generation and a variety of in vitro 3D cancer models are being explored for cancer drug discovery. Although homogeneous assay methods and high content imaging approaches to assess tumor spheroid morphology, growth and viability have been developed, the implementation of 3D models in HTS remains challenging due to reasons that we discuss in this review. Perhaps the biggest obstacle to achieve acceptable HTS assay performance metrics occurs in 3D tumor models that produce spheroids with highly variable morphologies and/or sizes. We highlight two methods that produce uniform size-controlled 3D multicellular tumor spheroids that are compatible with cancer drug research and HTS; tumor spheroids formed in ultra-low attachment microplates, or in polyethylene glycol dimethacrylate hydrogel microwell arrays. PMID:28647083

Antimalarial drug quality in Africa.

PubMed

Amin, A A; Kokwaro, G O

2007-10-01

There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. A search was conducted in PubMed in English using the medical subject headings (MeSH) terms: 'Antimalarials/analysis'[MeSH] OR 'Antimalarials/standards'[MeSH] AND 'Africa'[MeSH]' to include articles published up to and including 26 February 2007. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarized the data under the following themes: content and dissolution; relative bioavailability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that (i) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets, (ii) most antimalarial drugs pass the content test and (iii) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine-pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisinin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the continent have access to antimalarial drugs that are safe, of the highest quality standards and that retain their integrity throughout the distribution chain through adequate enforcement of existing legislation and enactment of new ones if necessary, and provision of the necessary resources for drug quality assurance.

ANTIMALARIAL DRUG QUALITY IN AFRICA

PubMed Central

Amin, AA; Kokwaro, GO

2009-01-01

Background and objective There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. Methods A search was conducted in PubMED in English using the medical subject headings (MeSH) terms: “Antimalarials/analysis”[MeSH] OR “Antimalarials/standards”[MeSH] AND “Africa”[MeSH]” to include articles published up to and including 26/02/07. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarised the data under the following themes: content and dissolution; relative bioavalability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. Results and discussion The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that 1) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets 2) most antimalarial drugs pass the content test 3) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine-pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. Conclusions There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the continent have access to antimalarial drugs that are safe, of the highest quality standards and that retain their integrity throughout the distribution chain through adequate enforcement of existing legislation and enactment of new ones if necessary, and provision of the necessary resources for drug quality assurance. PMID:17875107

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.

Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement.

PubMed

Krull, Scott M; Ma, Zhelun; Li, Meng; Davé, Rajesh N; Bilgili, Ecevit

2016-01-01

The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting-drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan-SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most <3% RSD) despite containing only 0.3-1.3 mg drug, which was ensured by the use of precursor suspensions with >5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t80 < 30 min) from films <120 μm thick. Thinner films, films with lower XG loading, or smaller drug particles led to faster drug dissolution, while drug loading had no discernible effect. Overall, these results suggest that pullulan may serve as an acceptable stabilizer for media milling in combination with surfactant as well as a fast-dissolving film former for the fast release of poorly water-soluble drug nanoparticles.

[The content-uniformity of dispensary-prepared rectal suppositories].

PubMed

Lüdde, H; Nestler, D

1990-01-01

Rectal suppositories, which are dispensed according prescription in small numbers up to N = 30, do not satisfy the demands in respect of content uniformity, if we consider the last N/10 poured ones. This by sedimentation caused problem is to be solved in increasing the amount of substances by N/10, so that you will get a safety-amount of 15% totally.

Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.

PubMed

Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

2015-06-01

The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30 s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15 s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5 min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution.

The success of the citizen suit: protecting consumers from inaccurate food labeling by amending the Federal Food, Drug, and Cosmetic Act.

PubMed

Springer, James

2013-01-01

The Federal Food, Drug, and Cosmetic Act ("FDCA"), amended in 1990 by the Nutrition Education and Labeling Act ("NLEA"), established a national framework for the administration and promulgation of uniform food labeling standards. Specifically, the NLEA created affirmative obligations for the food--requiring detailed disclosure of food content and strict adherence to regulations governing the use of health and nutritional claims on food packaging. To accomplish these goals, Congress tasked the Food and Drug Administration ("FDA") with the sole responsibility of the enforcement of these new requirements. Under the statutory framework of the FDCA, the United States Supreme Court ("Court") has held that there is no private right of action, of which extended to the enforcement of NLEA standards. This interpretation has left individuals with no federal outlet for relief in the enforcement of federal food labeling standards. Adherence to this interpretation is especially concerning when the FDA currently faces exponential growth in administrative responsibilities while simultaneously experiencing employment reduction, a $206 million "Sequester," and a recent government-wide shutdown. As a result, the American people are left to depend on an Agency that is struggling with drastic resource reduction while being accountable for ever increasing enforcement responsibilities. To ensure consumer protection, this Article argues that Congress should amend the FDCA to include a citizen suit provision in order to provide individuals with a right of private action for the enforcement of NLEA standards. Borrowing from the successes realized under similar citizen suit provisions found in environmental legislation, this Article argues that a citizen suit provision is amendable to the FDCA and would relieve fiscal pressures, strengthen the current enforcement framework of the FDCA, encourage more robust enforcement by the FDA and states, and ensure uniform interpretation of NLEA standards.

Poly(L-lactide)/halloysite nanotube electrospun mats as dual-drug delivery systems and their therapeutic efficacy in infected full-thickness burns.

PubMed

Zhang, Xiazhi; Guo, Rui; Xu, Jiqing; Lan, Yong; Jiao, Yanpeng; Zhou, Changren; Zhao, Yaowu

2015-11-01

In this study, poly(L-lactide) (PLLA)/halloysite nanotube (HNT) electrospun mats were prepared as a dual-drug delivery system. HNTs were used to encapsulate polymyxin B sulphate (a hydrophilic drug). Dexamethasone (a hydrophobic drug) was directly dissolved in the PLLA solution. The drug-loaded HNTs with optimised encapsulation efficiency were then mixed with the PLLA solution for subsequent electrospinning to form composite dual-drug-loaded fibre mats. The structure, morphology, degradability and mechanical properties of the electrospun composite mats were characterised in detail. The results showed that the HNTs were uniformly distributed in the composite PLLA mats. The HNTs content in the mats could change the morphology and average diameter of the electrospun fibres. The HNTs improved both the tensile strength of the PLLA electrospun mats and their degradation ratio. The drug-release kinetics of the electrospun mats were investigated using ultraviolet-visible spectrophotometry. The HNTs/PLLA ratio could be varied to adjust the release of polymyxin B sulphate and dexamethasone. The antibacterial activity in vitro of the mats was evaluated using agar diffusion and turbidimetry tests, which indicated the antibacterial efficacy of the dual-drug delivery system against Gram-positive and -negative bacteria. Healing in vivo of infected full-thickness burns and infected wounds was investigated by macroscopic observation, histological observation and immunohistochemical staining. The results indicated that the electrospun mats were capable of co-loading and co-delivering hydrophilic and hydrophobic drugs, and could potentially be used as novel antibacterial wound dressings. © The Author(s) 2015.

Adaptive removal of background and white space from document images using seam categorization

NASA Astrophysics Data System (ADS)

Fillion, Claude; Fan, Zhigang; Monga, Vishal

2011-03-01

Document images are obtained regularly by rasterization of document content and as scans of printed documents. Resizing via background and white space removal is often desired for better consumption of these images, whether on displays or in print. While white space and background are easy to identify in images, existing methods such as naïve removal and content aware resizing (seam carving) each have limitations that can lead to undesirable artifacts, such as uneven spacing between lines of text or poor arrangement of content. An adaptive method based on image content is hence needed. In this paper we propose an adaptive method to intelligently remove white space and background content from document images. Document images are different from pictorial images in structure. They typically contain objects (text letters, pictures and graphics) separated by uniform background, which include both white paper space and other uniform color background. Pixels in uniform background regions are excellent candidates for deletion if resizing is required, as they introduce less change in document content and style, compared with deletion of object pixels. We propose a background deletion method that exploits both local and global context. The method aims to retain the document structural information and image quality.

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

DOE PAGES

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan; ...

2017-03-03

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

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

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Design, formulation and evaluation of Aloe vera chewing gum

PubMed Central

Aslani, Abolfazl; Ghannadi, Alireza; Raddanipour, Razieh

2015-01-01

Background: Aloe vera has antioxidant, antiinflammatory, healing, antiseptic, anticancer and antidiabetic effects. The aim of the present study was to design and evaluate the formulation of Aloe vera chewing gum with an appropriate taste and quality with the indications for healing oral wounds, such as lichen planus, mouth sores caused by cancer chemotherapy and mouth abscesses as well as reducing mouth dryness caused by chemotherapy. Materials and Methods: In Aloe vera powder, the carbohydrate content was determined according to mannose and phenolic compounds in terms of gallic acid. Aloe vera powder, sugar, liquid glucose, glycerin, sweeteners and different flavors were added to the soft gum bases. In Aloe vera chewing gum formulation, 10% of dried Aloe vera extract entered the gum base. Then the chewing gum was cut into pieces of suitable sizes. Weight uniformity, content uniformity, the organoleptic properties evaluation, releasing the active ingredient in the phosphate buffer (pH, 6.8) and taste evaluation were examined by Latin square method. Results: One gram of Aloe vera powder contained 5.16 ± 0.25 mg/g of phenolic compounds and 104.63 ± 4.72 mg/g of carbohydrates. After making 16 Aloe vera chewing gum formulations, the F16 formulation was selected as the best formulation according to its physicochemical and organoleptic properties. In fact F16 formulation has suitable hardness, lack of adhesion to the tooth and appropriate size and taste; and after 30 min, it released more than 90% of its drug content. Conclusion: After assessments made, the F16 formulation with maltitol, aspartame and sugar sweeteners was selected as the best formulation. Among various flavors used, peppermint flavor which had the most acceptance between consumers was selected. PMID:26605214

Formulation and evaluation of Alendronate Sodium gel for the treatment of bone resorptive lesions in Periodontitis.

PubMed

Reddy, G Thirumal; Kumar, T M Pramod; Veena

2005-01-01

Alendronate sodium is formulated into gels and evaluated for the treatment of bone resorptive lesions in periodontitis. Carbopol 934P was used for the preparation of gels in three different concentrations. The prepared gel was evaluated for various properties such as preformulation, content uniformity, viscosity, compatibility, sterility, in vitro diffusion, and in vivo studies. The drug and the polymer were found to be compatible and confirmed by Fourier transform infrared spectroscopy. Viscosity of the gels increased with the increase in the polymer concentration. The formulations were found to be sterile. In vitro release study revealed that drug released from the gel follows non-Fickian diffusion followed by first-order release. In vivo studies were carried out for 6 months in patients. The results revealed a significant improvement in the clinical parameters such as gingival index, probing pocket depth, clinical attachment level, and potent inhibitory effect on bone resorption by inhibition of osteoclasts. In addition, there was increase in the new bone formation.

Preparation and characterization of spironolactone-loaded nano-emulsions for extemporaneous applications.

PubMed

Hallouard, François; Dollo, Gilles; Brandhonneur, Nolwenn; Grasset, Fabien; Corre, Pascal Le

2015-01-15

In neonates as well as in adults having swallowing difficulty, oral medication is given through a nasogastric tube making liquid formulations preferable. In this study, we present the high potential of nanometric emulsions formulated by spontaneous surfactant diffusion, as extemporaneous formulations of hydrophobic drug. Spironolactone used as hydrophobic drug model, was incorporated in oil before formulation at a concentration of 13.5mg/g oil. Then, all formulations were evaluated from pharmacotechnical and clinical standpoints, for their use in hospital or community pharmacy. The strength of this new liquid formulation lies on the simplicity, efficiency and reproducibility of their low energy process as on clinical aspects: high dose uniformity, facility to be administered through in nasogastric tube without any retention and a stability of 2 months at least compatible for an extemporaneous use. Moreover, this emulsion presented spironolactone content of 3.75 mg/ml among the most concentrated formulations published. Copyright © 2014 Elsevier B.V. All rights reserved.

Bilayer Tablet Formulation of Metformin HCl and Acarbose: A Novel Approach To Control Diabetes.

PubMed

Tiwari, Ruchi; Gupta, Ankita; Joshi, Meenakshi; Tiwari, Gaurav

2014-01-01

The present investigation studied a novel bilayer tablet having an extended release system of metformin HCl with Eudragit RS 100 and RL 100 and an immediate release system of acarbose with polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) in different ratios using solvent evaporation and cogrinding techniques. Solid dispersions (SDs) were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder x-ray diffractometry (XRD), scanning electron microscopy (SEM), as well as by content uniformity, in vitro dissolution studies, and release kinetics. The selected SD system was subjected to bilayer tablet preparation by direct compression. Compressed tablets were evaluated for drug content, weight variation, friability, hardness, and thickness, and they underwent in vitro dissolution studies. The progressive disappearance of IR, x-ray, and thermotropic drug signals in SDs and physical mixtures were related to increasing amount of polymer. SEM studies suggested the homogenous dispersion of drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between drug and polymer. All tablet formulations showed compliance with pharmacopoeial standards. The formulations gave an initial burst effect to provide the loading dose of the drug followed by extended release for 12 h (Higuchi model via a non-Fickian diffusion controlled release mechanism). Stability studies conducted for the optimized formulation did not show any change in physical properties, drug content, or in vitro drug release. The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of elevated blood glucose levels. Oral therapeutic options for the treatment of type 2 diabetes mellitus, until recently, have been severely limited. Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting hepatic glucose production and enhancing peripheral glucose uptake and thereby reducing insulin resistance; acarbose reversibly bind to pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes inhibit hydrolysis of complex starches to oligosaccharides in the lumen of the small intestine and hydrolysis of oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. The two agents were found to have a remarkable effect on glycemic control. In the present investigation a bilayer tablet was prepared in which one layer gives instant action against diabetes and another layer maintain concentration of drug in plasma for longer periods.

Formulation of Novel Layered Sodium Carboxymethylcellulose Film Wound Dressings with Ibuprofen for Alleviating Wound Pain

PubMed Central

Vinklárková, Lenka; Vetchý, David; Bernatonienė, Jurga

2015-01-01

Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT). To this end, an innovative solvent casting method using a sequential coating technique has been applied. The concentration of ibuprofen which was incorporated as an acetone solution or as a suspension in a sodium carboxymethylcellulose dispersion was 0.5 mg/cm2 and 1.0 mg/cm2 of film. Results showed that developed films had adequate mechanical and swelling properties and an advantageous acidic surface pH for wound application. An in vitro drug release study implied that layered films retained the drug for a longer period of time and thus could minimize the frequency of changing the dressing. Films with suspended ibuprofen demonstrated higher drug content uniformity and superior in vitro drug release characteristics in comparison with ibuprofen incorporation as an acetone solution. Prepared films could be potential wound dressings for the effective treatment of wound pain in low exuding wounds. PMID:26090454

[Optimizing the extracting technique of ampelopsin from Ampelopsis cantoniensis Planch by a uniform design method].

PubMed

He, Zhi-feng; Zeng, Sa; Hou, Juan-juan; Liu, De-yu

2006-07-01

To optimize the preparation of ampelopsin from Ampelopsis Cantoniensis Planch. The extraction and purification process was studied by the uniform design with the extract of ampelopsin content and purity as markers. The facters which influence the extraction and the purification of ampelopsin content were studied by uniform design. The optimum extraction and purification process: the concentration for alcohol was 90%, and refluxing quartic, 1.5 h each time; extraction by petroleum ether quintic, the mount of active carbon was 1 g/100 g of the medicine material, and recrystaling thrice. This extraction process has higher yield of ampelopsin and is available for production.

Spectrophotometric and spectrofluorimetric determination of indacaterol maleate in pure form and pharmaceutical preparations: application to content uniformity.

PubMed

El-Ashry, S M; El-Wasseef, D R; El-Sherbiny, D T; Salem, Y A

2015-09-01

Two simple, rapid, sensitive and precise spectrophotometric and spectrofluorimetric methods were developed for the determination of indacaterol maleate in bulk powder and capsules. Both methods were based on the direct measurement of the drug in methanol. In the spectrophotometric method (Method I) the absorbance was measured at 259 nm. The absorbance-concentration plot was rectilinear over the range 1.0-10.0 µg mL(-1) with a lower detection limit (LOD) of 0.078 µg mL(-1) and lower quantification limit (LOQ) of 0.238 µg mL(-1). Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence was measured at 358 nm after excitation at 258 nm. The fluorescence-concentration plot was rectilinear over the range of 1.0-40.0 ng mL(-1) with an LOD of 0.075 ng mL(-1) and an LOQ of 0.226 ng mL(-1). The proposed methods were successfully applied to the determination of indacaterol maleate in capsules with average percent recoveries ± RSD% of 99.94 ± 0.96 for Method I and 99.97 ± 0.81 for Method II. In addition, the proposed methods were extended to a content uniformity test according to the United States Pharmacopoeia (USP) guidelines and were accurate, precise for the capsules studied with acceptance value 3.98 for Method I and 2.616 for Method II. Copyright © 2015 John Wiley & Sons, Ltd.

Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets

PubMed Central

Aslani, Abolfazl; Jahangiri, Hajar

2013-01-01

Purpose: The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl) tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Methods: Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. Results: The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. Conclusion: In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame) were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties. PMID:24312854

78 FR 57623 - TRICARE Over-the-Counter Drug Demonstration Project

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-19

... DEPARTMENT OF DEFENSE Office of the Secretary TRICARE Over-the-Counter Drug Demonstration Project AGENCY: Office of the Secretary, DoD. ACTION: Notice of modification to the TRICARE Over-the-Counter Drug...) drugs to be included on the TRICARE uniform formulary. The Department has been engaged in a...

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

Effect of novel mucoadhesive buccal patches of carvedilol on isoprenaline-induced tachycardia

PubMed Central

Verma, Navneet; Chattopadhyay, Pronobesh

2014-01-01

The main aim of the study was designed to develop bioadhesive buccal patches of carvedilol (CR) and evaluate for isoprenaline-induced tachycardia. Buccal patches of carvedilol were prepared by using chitosan (CH), sodium salt of carboxy methyl cellulose (NaCMC), and polyvinyl alcohol (PVA) as mucoadhesive polymers. The solvent evaporation method was used for the preparation of buccal patches. The patches were evaluated for their physical characteristics like patch thickness, weight variation, content uniformity, folding endurance, surface pH, residence time, in vitro drug release, and in vivo pharmacodynamic study. The swelling index of the patches was found to be proportional to the polymer concentration, whereas surface pH of all the formulated bioadhesive patches was found to lie between neutral ranges. In-vitro release study shows that 94.75% drug was release in 8 hours from the patch, which containing 2% w/v chitosan. The folding endurance result shows good elasticity in all the patches. Application of buccal patches on buccal mucosa of rabbit shows a significant result in % inhibition of isoprenaline-induced tachycardia. Prepared buccal patches of chitosan, NaCMC, and PVA containing Carvedilol meet the ideal requirement for the delivery of cardiovascular drugs and inhibit the isoprenaline tachycardia. PMID:24959419

Effect of novel mucoadhesive buccal patches of carvedilol on isoprenaline-induced tachycardia.

PubMed

Verma, Navneet; Chattopadhyay, Pronobesh

2014-04-01

The main aim of the study was designed to develop bioadhesive buccal patches of carvedilol (CR) and evaluate for isoprenaline-induced tachycardia. Buccal patches of carvedilol were prepared by using chitosan (CH), sodium salt of carboxy methyl cellulose (NaCMC), and polyvinyl alcohol (PVA) as mucoadhesive polymers. The solvent evaporation method was used for the preparation of buccal patches. The patches were evaluated for their physical characteristics like patch thickness, weight variation, content uniformity, folding endurance, surface pH, residence time, in vitro drug release, and in vivo pharmacodynamic study. The swelling index of the patches was found to be proportional to the polymer concentration, whereas surface pH of all the formulated bioadhesive patches was found to lie between neutral ranges. In-vitro release study shows that 94.75% drug was release in 8 hours from the patch, which containing 2% w/v chitosan. The folding endurance result shows good elasticity in all the patches. Application of buccal patches on buccal mucosa of rabbit shows a significant result in % inhibition of isoprenaline-induced tachycardia. Prepared buccal patches of chitosan, NaCMC, and PVA containing Carvedilol meet the ideal requirement for the delivery of cardiovascular drugs and inhibit the isoprenaline tachycardia.

A novel concept for tumour targeting with radiation: Inverse dose-painting or targeting the "Low Drug Uptake Volume".

PubMed

Yaromina, Ala; Granzier, Marlies; Biemans, Rianne; Lieuwes, Natasja; van Elmpt, Wouter; Shakirin, Georgy; Dubois, Ludwig; Lambin, Philippe

2017-09-01

We tested a novel treatment approach combining (1) targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic tumour sub-volumes having no/low drug uptake. 18 F-HX4 hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV with the lowest or highest 18 F-HX4 uptake, respectively. Two hours post TH-302/saline administration, animals received either single dose radiotherapy (RT) uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50% higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse treatment planning system and radiation was delivered using VMAT. Tumour response was quantified as time to reach 3 times starting tumour volume. Non-uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average 3.5Gy lower dose to the GTV to achieve similar tumour response as uniform dose escalation. The results support targeted dose escalation to non-hypoxic tumour sub-volume with no/low activity of hypoxia-activated prodrugs. This strategy applies on average a lower radiation dose and is as effective as uniform dose escalation to the entire tumour. It could be applied to other type of drugs provided that their distribution can be imaged. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Suspensions as a Valuable Alternative to Extemporaneously Compounded Capsules.

PubMed

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Polonini, Hudson

2017-01-01

The objective of this study was to determine the variation in content of 74 different active pharmaceutical ingredients (APIs) and compare it with what is known in the literature for the content uniformity of extemporaneous prepared capsules. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography, via a stability-indicating method. Samples for all active pharmaceutical ingredients were taken throughout a 90-day period and the content was determined. In total, 5,190 different samples were analyzed for 74 different active pharmaceutical ingredients at room (15°C to 25°C) or controlled refrigerated temperature (2°C to 8°C). Each of these datasets was analyzed according to the United States Pharmacopeia Content Uniformity monograph, corrected for the sample number. The mean acceptance values were well within specifications. In addition, all suspensions complied with the criteria defined by the British Pharmacopoeia monograph for Content Uniformity of Liquid Dispersions for both room and controlled refrigerated temperature. In previous studies, it was found that a routine weight variation check is often not sufficient for quality assurance of extemporaneous prepared capsules. Compounded oral liquids show little variation in content for 74 different active pharmaceutical ingredients; therefore, compounded oral liquids are a suitable alternative when compounding individualized medications for patients. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

76 FR 54473 - Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... (formerly Docket No. 00D-0892)] Guidance on Positron Emission Tomography Drug Applications-- Content and... the availability of a guidance for industry entitled ``PET Drug Applications--Content and Format for... guidance for industry entitled ``PET Drug Applications--Content and Format for NDAs and ANDAs.'' The...

Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum

PubMed Central

Das, Sudipta; Bhatanagar, Suyash; Morrisey, Joanne M.; Daly, Thomas M.; Burns, James M.; Coppens, Isabelle; Vaidya, Akhil B.

2016-01-01

Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i) within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2), glycosylphosphotidylinositol (GPI)-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble “rhoptries” and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise. PMID:27227970

34 CFR 350.4 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 350.4 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 350.4 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 350.4 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 364.3 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... (Intergovernmental Review of Department of Education Programs and Activities). (6) 34 CFR part 80 (Uniform... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 364.3 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... (Intergovernmental Review of Department of Education Programs and Activities). (6) 34 CFR part 80 (Uniform... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 364.3 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... (Intergovernmental Review of Department of Education Programs and Activities). (6) 34 CFR part 80 (Uniform... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 364.3 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... (Intergovernmental Review of Department of Education Programs and Activities). (6) 34 CFR part 80 (Uniform... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 364.3 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... (Intergovernmental Review of Department of Education Programs and Activities). (6) 34 CFR part 80 (Uniform... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 636.6 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 636.6 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 654.4 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 636.6 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 636.6 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 654.4 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 654.4 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 654.4 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 636.6 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

34 CFR 654.4 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (8) 34 CFR part 86 (Drug-Free Schools and Campuses...

Formulation and Characterization of Fast-Dissolving Sublingual Film of Iloperidone Using Box-Behnken Design for Enhancement of Oral Bioavailability.

PubMed

Londhe, Vaishali; Shirsat, Rucha

2018-04-01

Iloperidone is a second-generation antipsychotic drug which is used for the treatment of schizophrenia and has very low aqueous solubility and bioavailability. This drug also undergoes first-pass metabolism. The aim of this work is to formulate fast-dissolving sublingual films of iloperidone to improve its bioavailability. Sublingual films were prepared by solvent casting method. Hydroxypropyl methyl cellulose E5, propylene glycol 400, and transcutol HP were optimized using Box-Behnken three-level statistical design on the basis of disintegration time and folding endurance of films. Iloperidone:hydroxypropyl-β-cyclodextrin kneaded complex was used in films instead of plain drug due to its low solubility. Optimized film was further evaluated for drug content, pH, dissolution studies, ex vivo permeation studies, and pharmacokinetic studies in rats. The optimized film disintegrated within 30 s. The in vitro dissolution of the film showed 80.3 ± 3.4% drug dissolved within first 5 min. In ex vivo permeation studies using sublingual tissue, flux achieved within first 15 min by film was around 117.1 ± 0.35 (mcg/cm 2 /h) which was ten times more than that of plain drug. This formulation showed excellent uniformity. AUC and C max of film were significantly higher (p < 0.001) as compared to plain drug and relative bioavailability of the films was 148% when compared to the plain drug. Thus, this study showed optimized fast-dissolving sublingual film to improve permeation and bioavailability of iloperidone. Fast-dissolving films will be customer-friendly approach for geadiatric schizophrenic patients.

Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

PubMed

Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-25

Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Orodispersible films in individualized pharmacotherapy: The development of a formulation for pharmacy preparations.

PubMed

Visser, J Carolina; Woerdenbag, Herman J; Crediet, Stefan; Gerrits, Edwin; Lesschen, Marjan A; Hinrichs, Wouter L J; Breitkreutz, Jörg; Frijlink, Henderik W

2015-01-15

Orodispersible films (ODFs) are promising drug delivery systems for customized small scale pharmacy preparations. The aim of the present study was to develop a versatile casting solution suitable for the extemporaneous production of ODFs to which active pharmaceutical ingredients (APIs) can be added. Different combinations of film forming agents and other excipients and different casting heights were tested for their suitability for production of ODFs. The best suitable casting solution contained hypromellose, carbomer, glycerol, disodium EDTA and trometamol. This casting solution was used to prepare ODFs containing water-soluble APIs (enalapril maleate and prednisolone disodium phosphate) and a poorly water-soluble API (diazepam) for which ethanol 96% was used as co-solvent.The water-soluble APIs as well as ethanol influenced the viscosity of the casting solution, mechanical properties and disintegration time of the ODFs. All ODFs containing API met the requirements on uniformity of mass and uniformity of content set by the European Pharmacopoeia (2014) (Ph. Eur.) 8th edition. In conclusion, ODFs of good pharmaceutical quality can be prepared on small scale. Hereby opening the perspective of using ODFs for individualized pharmacotherapy. Copyright © 2014 Elsevier B.V. All rights reserved.

34 CFR 381.4 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The...

34 CFR 381.4 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The...

34 CFR 381.4 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The...

34 CFR 381.4 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The...

34 CFR 381.4 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The...

The effect of particle morphology on the physical stability of pharmaceutical powder mixtures

NASA Astrophysics Data System (ADS)

Swaminathan, Vidya

Pharmaceutical powder mixtures are composed of particles that physically interact, precluding the formation of random mixtures. Mixtures based on particle interactions are termed ordered mixtures. The objective of this study was to determine the effect of the morphological characteristics of the components, surface texture and shape, along with size, on the formation of stable mixtures. Morphological parameters were obtained from image analysis measurements. Surface roughness was quantified using the ratio of the perimeter of the particle to that of an ideal shape (circle or square) having the same area; shape was described using the aspect ratio. The stability of mixtures of micronized aspirin with carriers of different surface roughness was determined by measuring the extent of drug adhering to the carrier after subjecting the mixtures to vibration. A lesser extent of segregation of drug from highly textured carriers relative to smoother textured carriers was observed. This was postulated to be due to a larger concentration of surface asperities on the coarser carriers which constitute potentially strong adhesion sites. The electrostatic charge on the powders was measured; differences in the response of the mixtures to the addition of magnesium stearate were attributed to electrostatic charge effects. The effect of varying the aspect ratio of the carrier and drug on segregation in polydisperse mixtures was determined from the coefficient of variation of the drug in the mixture as a function of mixing time. Reducing the size of the carrier resulted in poor homogeneity due to weak carrier-drug interactions. The variation in drug content resulting from a change in the shape of the carriers was smaller than that caused by size differences. The segregation rate constant in mixtures having dissimilarly shaped components was larger than in mixtures having components of similar shape. The effects of magnesium stearate concentration and lubrication time on the content uniformity of polydisperse mixtures were evaluated from a full factorial experiment. The segregation response of ordered and random mixtures to the addition of magnesium stearate was compared. The moisture sorption behavior of commercial magnesium stearate and the resulting morphological changes were evaluated.

PREPARATION AND CHARACTERIZATION OF ORALLY DISINTEGRATING LORATADINE TABLETS MANUFACTURED WITH CO-PROCESSED MIXTURES.

PubMed

Amelian, Aleksandra; Szekalska, Marta; Wilczewska, Agnieszka Zofia; Basa, Anna; Winnicka, Katarzyna

2016-01-01

The aim of this study was to develop orally disintegrated tablets (ODT) with loratadine using Parteck ODT and Ludiflash--new commercially available tableting excipients based on co-processed mannitol. ODT containing loratadine were prepared with 3% addition of various superdisintegrants (AcDiSol, Kollidon CL-F and Kollidon CL-SF) by direct compression method. Obtained tablets were characterized for friability, pore structure, and wetting and disintegration time measured by four independents methods. In order to identify possible interactions between loratadine and the excipients, differential scanning calorimetry was used. The results showed that all formulated ODT were characterized by appropriate mechanical properties (friability < 1%), the uniform content of the drug substance and pleasant mouth feeling. Disintegration time below 30 s was observed in formulations with crospovidones as disintegrant.

Formulation and in vitro characterization of xanthan gum-based sustained release matrix tables of isosorbide-5- mononitrate.

PubMed

Kar, Rajat; Mohapatra, Snehamayee; Bhanja, Satyabrata; Das, Debjyoti; Barik, Bhaktibhusan

2010-01-01

In the present investigation an attempt has been made to increase therapeutic efficacy, to reduce frequency of administration and to improve patient compliance by developing a sustained release matrix tablets of isosorbide-5-mononitrate. Sustained release matrix tablets of isosorbide-5-mononitrate were developed by using different drug: polymer ratios, such in F1 (1:0.75), F2 (1:1), F3 (1:1.5), F4 (1:1.75) and F6 (1:2). Xanthan gum was used as matrix former and microcrystalline cellulose as diluent. All the lubricated formulations were compressed, using 8mm flat faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution study using basket method and swelling index. Each formulation showed compliance with pharmacopoeial standards. Among all formulations, F5 showed a greater sustained release pattern of drug over a 12 h period with 92.12% of drug being released. The kinetic studies showed that drug release follows the Higuchi model (r(2) =0.9851). Korsemeyer and Peppas equation gave an n-value of 0.4566, which was close to 0.5, indicating that drug release follows the Fickian diffusion. Thus, xanthan gum can be used as an effective matrix former to extend the release of isosorbide-5-mononitrate. No significant difference was observed in the dissolution profile of optimized formulation, using basket and paddle apparatus.

Drug distribution and stability in extemporaneous preparations of meloxicam and carprofen after dilution and suspension at two storage temperatures.

PubMed

Hawkins, Michelle G; Karriker, Margo J; Wiebe, Valerie; Taylor, Ian T; Kass, Philip H

2006-09-15

To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days. Prospective study. Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively. Preparations were stored at approximately 4 degrees C (39.2 degrees F) or 22 degrees C (71.6 degrees F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated. In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation < 10%); > 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained > or = 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 +/- 0.04 and 0.21 +/- 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22 degrees C for 28 days yielded bacterial growth. DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.

Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery.

PubMed

He, Shuang; Li, Feng; Zhou, Dan; Du, Junrong; Huang, Yuan

2012-10-01

A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN's absorption at its absorption site and the efficacy of both CET and BN.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PubMed

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

2016-01-01

The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy.

PubMed

Parodi, Brunella; Russo, Eleonora; Baldassari, Sara; Zuccari, Guendalina; Pastorino, Sara; Yan, Mengying; Neduri, Karthik; Caviglioli, Gabriele

2017-06-01

The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone. A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application. The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8 min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation. HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.

21 CFR 1403.33 - Supplies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Supplies. 1403.33 Section 1403.33 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... supplies exceeding $5,000 in total aggregate fair market value upon termination or completion of the award...

21 CFR 1403.33 - Supplies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Supplies. 1403.33 Section 1403.33 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... supplies exceeding $5,000 in total aggregate fair market value upon termination or completion of the award...

21 CFR 1403.51 - Later disallowances and adjustments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Later disallowances and adjustments. 1403.51 Section 1403.51 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS... transactions; (c) Records retention as required in § 1403.42; (d) Property management requirements in § 1403.31...

21 CFR 1403.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Definitions. 1403.3 Section 1403.3 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... grantee is the entire legal entity even if only a particular component of the entity is designated in the...

21 CFR 1403.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Definitions. 1403.3 Section 1403.3 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... grantee is the entire legal entity even if only a particular component of the entity is designated in the...

21 CFR 1403.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Definitions. 1403.3 Section 1403.3 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... grantee is the entire legal entity even if only a particular component of the entity is designated in the...

21 CFR 1403.44 - Termination for convenience.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Termination for convenience. 1403.44 Section 1403.44 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR..., Retention, and Enforcement § 1403.44 Termination for convenience. Except as provided in § 1403.43 awards may...

21 CFR 1403.5 - Effect on other issuances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Effect on other issuances. 1403.5 Section 1403.5 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS General § 1403.5 Effect on other issuances...

21 CFR 1403.22 - Allowable costs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... the applicable cost principles. For the costs of a— Use the principles in— State, local or Indian...

21 CFR 1403.1 - Purpose and scope of this part.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Purpose and scope of this part. 1403.1 Section 1403.1 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR... agreements and subawards to State, local and Indian tribal governments. ...

21 CFR 1403.1 - Purpose and scope of this part.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Purpose and scope of this part. 1403.1 Section 1403.1 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR... agreements and subawards to State, local and Indian tribal governments. ...

21 CFR 1403.40 - Monitoring and reporting program performance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Monitoring and reporting program performance. 1403.40 Section 1403.40 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE... developments. Events may occur between the scheduled performance reporting dates which have significant impact...

Mixing Time Effects on the Dispersion Performance of Adhesive Mixtures for Inhalation

PubMed Central

Grasmeijer, Floris; Hagedoorn, Paul; Frijlink, Henderik W.; de Boer, H. Anne

2013-01-01

This paper deals with the effects of mixing time on the homogeneity and dispersion performance of adhesive mixtures for inhalation. Interactions between these effects and the carrier size fraction, the type of drug and the inhalation flow rate were studied. Furthermore, it was examined whether or not changes in the dispersion performance as a result of prolonged mixing can be explained with a balance of three processes that occur during mixing, knowing drug redistribution over the lactose carrier; (de-) agglomeration of the drug (and fine lactose) particles; and compression of the drug particles onto the carrier surface. For this purpose, mixtures containing salmeterol xinafoate or fluticasone propionate were mixed for different periods of time with a fine or coarse crystalline lactose carrier in a Turbula mixer. Drug detachment experiments were performed using a classifier based inhaler at different flow rates. Scanning electron microscopy and laser diffraction techniques were used to measure drug distribution and agglomeration, whereas changes in the apparent solubility were measured as a means to monitor the degree of mechanical stress imparted on the drug particles. No clear trend between mixing time and content uniformity was observed. Quantitative and qualitative interactions between the effect of mixing time on drug detachment and the type of drug, the carrier size fraction and the flow rate were measured, which could be explained with the three processes mentioned. Generally, prolonged mixing caused drug detachment to decrease, with the strongest decline occurring in the first 120 minutes of mixing. For the most cohesive drug (salmeterol) and the coarse carrier, agglomerate formation seemed to dominate the overall effect of mixing time at a low inhalation flow rate, causing drug detachment to increase with prolonged mixing. The optimal mixing time will thus depend on the formulation purpose and the choice for other, interacting variables. PMID:23844256

Application of a handheld NIR spectrometer in prediction of drug content in inkjet printed orodispersible formulations containing prednisolone and levothyroxine.

PubMed

Vakili, Hossein; Wickström, Henrika; Desai, Diti; Preis, Maren; Sandler, Niklas

2017-05-30

Quality control tools to assess the quality of printable orodispersible formulations are yet to be defined. Four different orodispersible dosage forms containing two poorly soluble drugs, levothyroxine and prednisolone, were produced on two different edible substrates by piezoelectric inkjet printing. Square shaped units of 4cm 2 were printed in different resolutions to achieve an escalating drug dose by highly accurate and uniform displacement of droplets in picoliter range from the printhead onto the substrates. In addition, the stability of drug inks in a course of 24h as well as the mechanical properties and disintegration behavior of the printed units were examined. A compact handheld near-infrared (NIR) spectral device in the range of 1550-1950nm was used for quantitative estimation of the drug amount in printed formulations. The spectral data was treated with mean centering, Savitzky-Golay filtering and a third derivative approach. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) regression were applied to build predictive models for quality control of the printed dosage forms. The accurate tuning of the dose in each formulation was confirmed by UV spectrophotometry for prednisolone (0.43-1.95mg with R 2 =0.999) and high performance liquid chromatography for levothyroxine (0.15-0.86mg with R 2 =0.997). It was verified that the models were capable of clustering and predicting the drug dose in the formulations with both Q 2 and R 2 Y values between 0.94-0.99. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology.

PubMed

McConville, Christopher; Major, Ian; Devlin, Brid; Brimer, Andrew

2016-07-01

Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation and In Vitro Characterization of Thiolated Buccoadhesive Film of Fluconazole.

PubMed

Naz, Kiran; Shahnaz, Gul; Ahmed, Naveed; Qureshi, Naveeda Akhtar; Sarwar, Hafiz Shoaib; Imran, Muhammad; Khan, Gul Majid

2017-05-01

The present work is focused on the development of thiolated film for fluconazole buccal delivery. To this end, unmodified polymers chitosan and sodium carboxymethylcellulose (NaCMC) backbone was covalently modified by thioglycolic acid (TGA) and cysteine, respectively. The thiolated buccoadhesive film was evaluated in terms of thickness, weight uniformity, water-uptake capacity, drug content, and release patterns. Moreover, mucoadhesion profile was investigated on buccal mucosa. The resulting chitosan-TGA and NaCMC-cysteine conjugates displayed 171 ± 13 and 380 ± 19 μmol thiol groups per gram of polymer (mean ± SD; n = 3), respectively. The water binding capacity of the thiolated film was significantly ∼2-fold higher (p < 0.05) as compared to unmodified film. The obtained thiolated film displayed 5.8-fold higher mucoadhesive properties compared with corresponding film. Controlled release of drugs from film was observed over 8 h. The transport of fluconazole across excised buccal mucosa was enhanced up to 17-fold in comparison with fluconazole applied in buffer. Based on these findings, thiolated film seems to be promising for fluconazole buccal delivery.

Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

PubMed

Hammad, Mohamed A; Omar, Mahmoud A; Salman, Baher I

2017-09-01

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml -1 , with quantitation limits 27.1 and 32.2 ng ml -1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy. Copyright © 2017 John Wiley & Sons, Ltd.

Drug release from slabs and the effects of surface roughness.

PubMed

Kalosakas, George; Martini, Dimitra

2015-12-30

We discuss diffusion-controlled drug release from slabs or thin films. Analytical and numerical results are presented for slabs with flat surfaces, having a uniform thickness. Then, considering slabs with rough surfaces, the influence of a non-uniform slab thickness on release kinetics is numerically investigated. The numerical release profiles are obtained using Monte Carlo simulations. Release kinetics is quantified through the stretched exponential (or Weibull) function and the resulting dependence of the two parameters of this function on the thickness of the slab, for flat surfaces, and the amplitude of surface fluctuations (or the degree of thickness variability) in case of roughness. We find that a higher surface roughness leads to a faster drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

Design and physicochemical stability studies of paediatric oral formulations of sildenafil.

PubMed

Provenza, N; Calpena, A C; Mallandrich, M; Halbaut, L; Clares, B

2014-01-02

Personalized medicine is a challenging research area in paediatric treatments. Elaborating new paediatric formulations when no commercial forms are available is a common practice in pharmacy laboratories; among these, oral liquid formulations are the most common. But due to the lack of specialized equipment, frequently studies to assure the efficiency and safety of the final medicine cannot be carried out. Thus the purpose of this work was the development, characterization and stability evaluation of two oral formulations of sildenafil for the treatment of neonatal persistent pulmonary hypertension. After the establishment of a standard operating procedure (SOP) and elaboration, the physicochemical stability parameters appearance, pH, particle size, rheological behaviour and drug content of formulations were evaluated at three different temperatures for 90 days. Equally, prediction of long term stability, as well as, microbiological stability was performed. Formulations resulted in a suspension and a solution slightly coloured exhibiting fruity odour. Formulation I (suspension) exhibited the best physicochemical properties including Newtonian behaviour and uniformity of API content above 90% to assure an exact dosification process. Copyright © 2013 Elsevier B.V. All rights reserved.

Messages discriminated from the media about illicit drugs.

PubMed

Patterson, S J

1994-01-01

The electronic media have been an instrumental tool in the most recent efforts to address the issue of illicit drug abuse in the United States. Messages about illicit drugs appear in three places in the media: advertising content, news content, and entertainment content. Many studies have documented the amount and types of messages that appear on the electronic media, but few have asked the audience how they interpret these messages. The purpose of this study is to investigate how much and what type of information college students receive from the media about drugs. Interviews were conducted with 228 students using the message discrimination protocol. The messages were then content analyzed into theme areas. Results indicate the majority of messages discriminated from advertising content were fear appeals; that the majority of messages discriminated from news content documented the enforcement efforts in the war on drugs; and that messages about drugs in entertainment content were more likely to provide clear accurate information about drugs than the other two content sources. The results are discussed in terms of the audience receiving fear and fight messages from the electronic media rather than clear, accurate information necessary to make informed decisions about drugs.

Quality evaluation and in vitro interaction studies between levofloxacin 250mg and diclofenac sodium 50mg tablets.

PubMed

Fayyaz, Muhammad; Yousuf, Rabia Ismail; Shoaib, Muhammad Harris; Ali, Tariq; Nasiri, Iqbal; Ashraf, Nida

2015-01-01

Fluoroquinolones are broad-spectrum antibiotics, work against Gram-positive and Gram-negative bacteria and are a clinically proven option for many resistant infections. Among fluoroquinolones Levofloxacin works best against acute sinusitis, inflammation of the lower airways, acute exacerbation of chronic bronchitis, community acquired pneumonia, complicated urinary tract infection including Pyelonephritis, chronic bacterial prostatitis and skin and soft tissue infection. Levofloxacin is a frequently prescribed antibacterial agent with Diclofenac Sodium for pain management in infectious conditions. The objective of the present work is to evaluate the level of interaction between Levofloxacin and Diclofenac Sodium. In this work market available brands of both drugs were also evaluated for quality.The physiochemical parameters like weight variation, thickness variation, and mechanical strength were determined. Similarly the percentage drug release and content uniformity test were also analyzed; the tested quality attributes were found within the recommended pharmacopeia ranges except brand L(6) that had high drug content 124.629±3.614 while brand L(4) and L(5) were not found similar in pH 1.2. When subjected to model dependent analysis Levofloxacin showed compliance with (first order, Higuchi, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8). However Diclofenac Sodium showed adherence with (first order, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8) but following Higuchi at pH 1.2 and 4.5 only. The interaction studies were also performed spectrophotometrically and simultaneous equation was used to estimate the percentage availability of both the drugs at pH 4.5, 6.8, FaSSGF and FaSSIF. The studies showed that the percent availability of Levofloxacin was increased significantly in FaSSIF i.e. 129.173±0.323 at 45 minutes in the presence of Diclofenac Sodium.

77 FR 38019 - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/TRICARE: TRICARE Retail...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-26

... prescriptions approved through the non-formulary special approval process that validates the medical necessity... the process for formulary placement of newly approved drugs; streamline the process for updating... clarify the process for formulary placement of newly approved drugs by the Food and Drug Administration...

Evaluation of Characteristic Energy Scales of Pressure Stabilized Oxygen Chain States in YBa2Cu3Ox Films

DTIC Science & Technology

2017-03-14

2], and [4]. In the case of YBa2Cu3O∇x, the application of sufficient uniaxial pressure results in the film having discrete regions of uniform...that discrete regions of uniform oxygen content are stabilized where x ≈ [6, 6.5, 6.72, 6.81, 7]. The latter four oxygen content levels correspond to...associated energy levels of the stabilized lattice states ᝺>, �>, >, and ə>, and find evidence for discrete energy levels of the pressure

Continuous direct compression as manufacturing platform for sustained release tablets.

PubMed

Van Snick, B; Holman, J; Cunningham, C; Kumar, A; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2017-03-15

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of sustained release tablets was crucial to ensure reproducible dissolution. Copyright © 2017 Elsevier B.V. All rights reserved.

5 CFR 1208.13 - Content of appeal; request for hearing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Content of appeal; request for hearing... PROCEDURES PRACTICES AND PROCEDURES FOR APPEALS UNDER THE UNIFORMED SERVICES EMPLOYMENT AND REEMPLOYMENT RIGHTS ACT AND THE VETERANS EMPLOYMENT OPPORTUNITIES ACT USERRA Appeals § 1208.13 Content of appeal...

5 CFR 1208.23 - Content of appeal; request for hearing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Content of appeal; request for hearing... PROCEDURES PRACTICES AND PROCEDURES FOR APPEALS UNDER THE UNIFORMED SERVICES EMPLOYMENT AND REEMPLOYMENT RIGHTS ACT AND THE VETERANS EMPLOYMENT OPPORTUNITIES ACT VEOA Appeals § 1208.23 Content of appeal...

26 CFR 1.401(l)-0 - Table of contents.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... (5) Prorated integration level for short plan year. (e) Examples. § 1.401(l)-3Permitted disparity for... forms. (D) Post-retirement cost-of-living adjustments. (1) In general. (2) Requirements. (E) Section 417(e) exception. (5) Examples. (c) Uniform disparity. (1) In general. (2) Deemed uniformity. (i) In...

26 CFR 1.401(l)-0 - Table of contents.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (5) Prorated integration level for short plan year. (e) Examples. § 1.401(l)-3Permitted disparity for... forms. (D) Post-retirement cost-of-living adjustments. (1) In general. (2) Requirements. (E) Section 417(e) exception. (5) Examples. (c) Uniform disparity. (1) In general. (2) Deemed uniformity. (i) In...

26 CFR 1.401(l)-0 - Table of contents.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (5) Prorated integration level for short plan year. (e) Examples. § 1.401(l)-3Permitted disparity for... forms. (D) Post-retirement cost-of-living adjustments. (1) In general. (2) Requirements. (E) Section 417(e) exception. (5) Examples. (c) Uniform disparity. (1) In general. (2) Deemed uniformity. (i) In...

A method for fast selecting feature wavelengths from the spectral information of crop nitrogen

USDA-ARS?s Scientific Manuscript database

Research on a method for fast selecting feature wavelengths from the nitrogen spectral information is necessary, which can determine the nitrogen content of crops. Based on the uniformity of uniform design, this paper proposed an improved particle swarm optimization (PSO) method. The method can ch...

Informational and symbolic content of over-the-counter drug advertising on television.

PubMed

Tsao, J C

1997-01-01

The informational and symbolic content of 150 over-the-counter drug commercials on television are empirically analyzed in this study. Results on the informational content suggest that over-the-counter drug ads tend to focus on the concern of what the drug will do for the consumer, rather than on the reasons why the drug should be ingested. Accordingly, advertising strategy is centered on consumer awareness of the product as the primary goal. Educational commitment, however, did not seem to be blended into the promotional efforts for over-the-counter drugs. Findings on the symbolic content of over-the-counter drug ads reveal that drug images have been distorted. Performance of most drugs has been portrayed to be simple resolutions to relieve the symptom. Moreover, a casual attitude toward drug usage is encouraged in the commercials, while time lapse of drug effects is overlooked.

34 CFR 400.3 - What other regulations apply to the Vocational and Applied Technology Education Programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... applicable to parts 401, 410, 411, 413, 418, and 419). (6) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 400.3 - What other regulations apply to the Vocational and Applied Technology Education Programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... applicable to parts 401, 410, 411, 413, 418, and 419). (6) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

34 CFR 400.3 - What other regulations apply to the Vocational and Applied Technology Education Programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... applicable to parts 401, 410, 411, 413, 418, and 419). (6) 34 CFR part 80 (Uniform Administrative... Governmentwide Requirements for Drug-Free Workplace (Grants)). (10) 34 CFR part 86 (Drug-Free Schools and...

Uniform magnetic targeting of magnetic particles attracted by a new ferromagnetic biological patch.

PubMed

Pei, Ning; Cai, Lanlan; Yang, Kai; Ma, Jiaqi; Gong, Yongyong; Wang, Qixin; Huang, Zheyong

2018-02-01

A new non-toxic ferromagnetic biological patch (MBP) was designed in this paper. The MBP consisted of two external layers that were made of transparent silicone, and an internal layer that was made of a mixture of pure iron powder and silicon rubber. Finite-element analysis showed that the local inhomogeneous magnetic field (MF) around the MBP was generated when MBP was placed in a uniform MF. The local MF near the MBP varied with the uniform MF and shape of the MBP. Therefore, not only could the accumulation of paramagnetic particles be adjusted by controlling the strength of the uniform MF, but also the distribution of the paramagnetic particles could be improved with the different shape of the MBP. The relationship of the accumulation of paramagnetic particles or cells, magnetic flux density, and fluid velocity were studied through in vitro experiments and theoretical considerations. The accumulation of paramagnetic particles first increased with increment in the magnetic flux density of the uniform MF. But when the magnetic flux density of the uniform MF exceeded a specific value, the magnetic flux density of the MBP reached saturation, causing the accumulation of paramagnetic particles to fall. In addition, the adsorption morphology of magnetic particles or cells could be improved and the uniform distribution of magnetic particles could be achieved by changing the shape of the MBP. Also, MBP may be used as a new implant to attract magnetic drug carrier particles in magnetic drug targeting. Bioelectromagnetics. 39:98-107, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Backwards compatible high dynamic range video compression

NASA Astrophysics Data System (ADS)

Dolzhenko, Vladimir; Chesnokov, Vyacheslav; Edirisinghe, Eran A.

2014-02-01

This paper presents a two layer CODEC architecture for high dynamic range video compression. The base layer contains the tone mapped video stream encoded with 8 bits per component which can be decoded using conventional equipment. The base layer content is optimized for rendering on low dynamic range displays. The enhancement layer contains the image difference, in perceptually uniform color space, between the result of inverse tone mapped base layer content and the original video stream. Prediction of the high dynamic range content reduces the redundancy in the transmitted data while still preserves highlights and out-of-gamut colors. Perceptually uniform colorspace enables using standard ratedistortion optimization algorithms. We present techniques for efficient implementation and encoding of non-uniform tone mapping operators with low overhead in terms of bitstream size and number of operations. The transform representation is based on human vision system model and suitable for global and local tone mapping operators. The compression techniques include predicting the transform parameters from previously decoded frames and from already decoded data for current frame. Different video compression techniques are compared: backwards compatible and non-backwards compatible using AVC and HEVC codecs.

21 CFR 201.51 - Declaration of net quantity of contents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Prescription Drugs and/or Insulin § 201.51 Declaration of net quantity of contents. (a) The label of a prescription or insulin-containing drug in package....). A statement of the liquid measure of the contents in the case of insulin-containing drugs shall be...

21 CFR 201.51 - Declaration of net quantity of contents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Prescription Drugs and/or Insulin § 201.51 Declaration of net quantity of contents. (a) The label of a prescription or insulin-containing drug in package....). A statement of the liquid measure of the contents in the case of insulin-containing drugs shall be...

21 CFR 201.51 - Declaration of net quantity of contents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Prescription Drugs and/or Insulin § 201.51 Declaration of net quantity of contents. (a) The label of a prescription or insulin-containing drug in package....). A statement of the liquid measure of the contents in the case of insulin-containing drugs shall be...

21 CFR 201.51 - Declaration of net quantity of contents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Prescription Drugs and/or Insulin § 201.51 Declaration of net quantity of contents. (a) The label of a prescription or insulin-containing drug in package....). A statement of the liquid measure of the contents in the case of insulin-containing drugs shall be...

21 CFR 201.51 - Declaration of net quantity of contents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Prescription Drugs and/or Insulin § 201.51 Declaration of net quantity of contents. (a) The label of a prescription or insulin-containing drug in package....). A statement of the liquid measure of the contents in the case of insulin-containing drugs shall be...

Optimization of biodegradable sponges as controlled release drug matrices. I. Effect of moisture level on chitosan sponge mechanical properties.

PubMed

Foda, Nagwa H; El-laithy, Hanan M; Tadros, Mina I

2004-04-01

Cross-linked chitosan sponges as controlled release drug carrier systems were developed. Tramadol hydrochloride, a centrally acting analgesic, was used as a model drug. The sponges were prepared by freeze-drying 1.25% and 2.5% (w/w) high and low M.wt. chitosan solutions, respectively, using glutaraldehyde as a cross-linking agent. The hardness of the prepared sponges was a function of glutaraldehyde concentration and volume where the optimum concentration that offered accepted sponge consistency was 5%. Below or above 5%, very soft or very hard and brittle sponges were obtained, respectively. The determined drug content in the prepared sponges was uniform and did not deviate markedly from the calculated amount. Scanning electron microscopy (SEM) was used to characterize the internal structures of the sponges. The SEM photos revealed that cross-linked high M.wt. chitosan sponges have larger size surface pores that form connections (channels) with the interior of the sponge than cross-linked low M.wt. ones. Moreover, crystals of the incorporated Tramadol hydrochloride were detected on the lamellae and within pores in both chitosan sponges. Differences in pore size and dissolution medium uptake capacity were crucial factors for the more delayed drug release from cross-linked low M.wt. chitosan sponges over high M.wt. ones at pH 7.4. Kinetic analysis of the release data using linear regression followed the Higuchi diffusion model over 12 hours. Setting storage conditions at room temperature under 80-92% relative humidity resulted in soft, elastic, and compressible sponges.

Antimicrobial gelatin-based elastomer nanocomposite membrane loaded with ciprofloxacin and polymyxin B sulfate in halloysite nanotubes for wound dressing.

PubMed

Shi, Rui; Niu, Yuzhao; Gong, Min; Ye, Jingjing; Tian, Wei; Zhang, Liqun

2018-06-01

Bacterial infection is a major problem world-wide, especially in wound treatment where it can severely prolong the healing process. In this study, a double drug co-delivery elastic antibacterial nanocomposite was developed by combining ciprofloxacin (CPX) and polymyxin B sulfate-loaded halloysite clay nanotubes (HNTs-B) into a gelatin elastomer. CPX nanoparticles which act against both gram positive and gram-negative bacterium were dispersed directly in the matrix, and polymyxin B sulfate was loaded in HNTs and then distributed into the matrix. The effect of CPX and HNTs-B content on the physical properties, cytotoxicity, fibroblast adhesion and proliferation, in vitro drug release behavior and anti-bacterial properties were systematically investigated. The ciprofloxacin crystals and HNT-B were distributed in the matrix uniformly. The HNTs in the drug loading system not only enhanced the matrix' tensile strength but also slowed down the release rate of the high dissoluble polymyxin B sulfate. When the amount of HNT in the matrix increased, the thermal stability and tensile strength also increased but the polymyxin B sulfate release rate decreased because the HNTs prevented the drug release inside. All the nanocomposites exhibited antimicrobial activity against both gram-negative and gram-positive bacteria with the dual combination of drugs released from the nanocomposites. Furthermore, this kind of gelatin-based nanocomposites possesses higher water-absorbing quality, low cytotoxicity, adaptable biodegradability and good elasticity which can satisfy the requirements for an ideal biomaterial for use in wound healing applications. Copyright © 2018. Published by Elsevier B.V.

Evolution of AlGaN deep level defects as a function of alloying and compositional grading and resultant impact on electrical conductivity

DOE PAGES

Armstrong, Andrew M.; Allerman, Andrew A.

2017-07-24

AlGaN:Si epilayers with uniform Al compositions of 60%, 70%, 80%, and 90% were grown by metal-organic vapor phase epitaxy along with a compositionally graded, unintentionally doped (UID) AlGaN epilayer with the Al composition varying linearly between 80% and 100%. The resistivity of AlGaN:Si with a uniform composition increased significantly for the Al content of 80% and greater, whereas the graded UID-AlGaN film exhibited resistivity equivalent to 60% and 70% AlGaN:Si owing to polarization-induced doping. Deep level defect studies of both types of AlGaN epilayers were performed to determine why the electronic properties of uniform-composition AlGaN:Si degraded with increased Al content,more » while the electronic properties of graded UID-AlGaN did not. The deep level density of uniform-composition AlGaN:Si increased monotonically and significantly with the Al mole fraction. Conversely, graded-UID AlGaN had the lowest deep level density of all the epilayers despite containing the highest Al composition. These findings indicate that Si doping is an impetus for point defect incorporation in AlGaN that becomes stronger with the increasing Al content. However, the increase in deep level density with the Al content in uniform-composition AlGaN:Si was small compared to the increase in resistivity. This implies that the primary cause for increasing resistivity in AlGaN:Si with the increasing Al mole fraction is not compensation by deep levels but rather increasing activation energy for the Si dopant. As a result, the graded UID-AlGaN films maintained low resistivity because they do not rely on thermal ionization of Si dopants.« less

Evolution of AlGaN deep level defects as a function of alloying and compositional grading and resultant impact on electrical conductivity

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

Armstrong, Andrew M.; Allerman, Andrew A.

AlGaN:Si epilayers with uniform Al compositions of 60%, 70%, 80%, and 90% were grown by metal-organic vapor phase epitaxy along with a compositionally graded, unintentionally doped (UID) AlGaN epilayer with the Al composition varying linearly between 80% and 100%. The resistivity of AlGaN:Si with a uniform composition increased significantly for the Al content of 80% and greater, whereas the graded UID-AlGaN film exhibited resistivity equivalent to 60% and 70% AlGaN:Si owing to polarization-induced doping. Deep level defect studies of both types of AlGaN epilayers were performed to determine why the electronic properties of uniform-composition AlGaN:Si degraded with increased Al content,more » while the electronic properties of graded UID-AlGaN did not. The deep level density of uniform-composition AlGaN:Si increased monotonically and significantly with the Al mole fraction. Conversely, graded-UID AlGaN had the lowest deep level density of all the epilayers despite containing the highest Al composition. These findings indicate that Si doping is an impetus for point defect incorporation in AlGaN that becomes stronger with the increasing Al content. However, the increase in deep level density with the Al content in uniform-composition AlGaN:Si was small compared to the increase in resistivity. This implies that the primary cause for increasing resistivity in AlGaN:Si with the increasing Al mole fraction is not compensation by deep levels but rather increasing activation energy for the Si dopant. As a result, the graded UID-AlGaN films maintained low resistivity because they do not rely on thermal ionization of Si dopants.« less

Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

NASA Astrophysics Data System (ADS)

Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

2016-02-01

Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

Effects of uniformities of deposition of respirable particles on filters on determining their quartz contents by using the direct on-filter X-ray diffraction (DOF XRD) method.

PubMed

Chen, Ching-Hwa; Tsaia, Perng-Jy; Lai, Chane-Yu; Peng, Ya-Lian; Soo, Jhy-Charm; Chen, Cheng-Yao; Shih, Tung-Sheng

2010-04-15

In this study, field samplings were conducted in three workplaces of a foundry plant, including the molding, demolding, and bead blasting, respectively. Three respirable aerosol samplers (including a 25-mm aluminum cyclone, nylon cyclone, and IOSH cyclone) were used side-by-side to collect samples from each selected workplace. For each collected sample, the uniformity of the deposition of respirable dusts on the filter was measured and its free silica content was determined by both the DOF XRD method and NIOSH 7500 XRD method (i.e., the reference method). A same trend in measured uniformities can be found in all selected workplaces: 25-mm aluminum cyclone>nylon cyclone>IOSH cyclone. Even for samples collected by the sampler with the highest uniformity (i.e., 25-mm aluminum cyclone), the use of the DOF XRD method would lead to the measured free silica concentrations 1.15-2.89 times in magnitude higher than that of the reference method. A new filter holder should be developed with the minimum uniformity comparable to that of NIOSH 7500 XRD method (=0.78) in the future. The use of conversion factors for correcting quartz concentrations obtained from the DOF XRD method based on the measured uniformities could be suitable for the foundry industry at this stage. 2009 Elsevier B.V. All rights reserved.

Magnetic Resonance Imaging of Heart Failure Using a Swine Model

DTIC Science & Technology

2011-03-21

Defense or the Uniformed Services University of the Health Sciences. / Ma een N. Hood, MR, RN, RT (R)(MR), FSMRT Gr duate School of Nursing U iformed...2652710212087 License date Apr 19, 2011 Licensed content publisher Wolters Kluwer Health Licensed content publication Journal of Cardiovascular Nursing ...Licensed content title A Review of Cohort Study Design for Cardiovascular Nursing Research Licensed content author Maureen Hood Licensed content date Jan

Ethylcellulose film coating of guaifenesin-loaded pellets: A comprehensive evaluation of the manufacturing process to prevent drug migration.

PubMed

Melegari, Cecilia; Bertoni, Serena; Genovesi, Alberto; Hughes, Kevin; Rajabi-Siahboomi, Ali R; Passerini, Nadia; Albertini, Beatrice

2016-03-01

The aim of the research was to investigate the complete process of pellet production in a Wurster fluidized bed coater in order to determine the main factors affecting the migration phenomenon of a soluble API through the ethycellulose film coating (Surelease®) and hence the long-term stability of the controlled release pellets. Guaifenesin (GFN), as BCS class I model drug, was layered on sugar spheres using a binder-polymer solution containing the dissolved GFN. The drug loaded pellets were then coated with Surelease®. The influence of drug loading (4.5-20.0% w/w), curing conditions (40-60°C and dynamic-static equipment), coating level (12-20% theoretical weight gain) and composition of the binder-layering solution (hypromellose versus Na alginate) on process efficiency (RSDW%), GFN content uniformity (RSDC%), GFN solid state (DSC and XRD) and pellet release profiles was evaluated. The effectiveness of the Surelease film was strongly affected by the ability of GFN to cross the coating layer and to recrystallize on the pellet surface. Results indicated that this behaviour was dependent on the polymer used in the binder-layering solution. Using hypromellose as polymer, GFN recrystallized on the coated pellet surface at both drug loadings. The curing step was necessary to stabilize the film effectiveness at the higher drug loading. Increasing the coating level delayed but did not prevent the GFN diffusion. Replacing hypromellose with Na alginate, reduced the migration of GFN through the film to a negligible amount even after six months of storage and the curing step was not necessary to achieve stable controlled release profiles over storage. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-01-01

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

Feasibility studies of concomitant administration of optimized formulation of probiotic-loaded Vancomycin hydrochloride pellets for colon delivery.

PubMed

Avachat, Amelia M; Shinde, Amol S

2016-01-01

Objective of this study was to develop Vancomycin HCl pellets loaded with Saccharomyces boulardii (S.b.) for pH-dependent system and CODES™ for augmenting the efficacy of Vancomycin HCl in the treatment of colitis. Pellets were prepared by extrusion-spheronization. In the pH-dependent system, the pellets were coated with Eudragit FS 30D. These pellets exhibited spherical form and a uniform surface coating. The CODES™ system consisted of three components: core containing mannitol, drug and probiotic, an inner acid-soluble coating layer, and an outer layer of enteric coating material. Statistical factorial design was used to optimize both formulations. Scanning electron micrographs of coated pellets revealed uniform coating. In vitro drug release of these coated pellets was studied sequentially in various buffers with (2%) and without rat cecal content for a period of 12 h. From the optimized pH-dependent formulation, F6 (20% w/w coating level and 15% w/v concentration of polymer), higher amount of probiotic was released in earlier time phase (first 5 h) as compared to the CODES™ and so R5 [containing acid-soluble inner coating layer (15% w/w coating level and 12% w/v concentration of Eudragit E100), and an outer layer of enteric coating material (12% w/w coating level and 10% w/v concentration of Eudragit L100)] was considered as the best formulation after confirming in vivo X-ray studies conducted on rabbits, suggesting that Vancomycin HCl and S.b. may be co-administered as pellets [CODES™] to enhance the effectiveness of Vancomycin HCl in the treatment of colitis without its associated side effects, which can only be confirmed after clinical trials.

Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability.

PubMed

De Caro, Viviana; Ajovalasit, Alessia; Sutera, Flavia Maria; Murgia, Denise; Sabatino, Maria Antonietta; Dispenza, Clelia

2017-06-24

Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young's Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m². FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

PubMed Central

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed MA; Hassan, Omiya A

2016-01-01

Purpose The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Materials and methods Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). Conclusion The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. PMID:28008229

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

Adherence to the Australian National Inpatient Medication Chart: the efficacy of a uniform national drug chart on improving prescription error.

PubMed

Atik, Alp

2013-10-01

In 2006, the National Inpatient Medication Chart (NIMC) was introduced as a uniform medication chart in Australian public hospitals with the aim of reducing prescription error. The rate of regular medication prescription error in the NIMC was assessed. Data was collected using the NIMC Audit Tool and analyzed with respect to causes of error per medication prescription and per medication chart. The following prescription requirements were assessed: date, generic drug name, route of administration, dose, frequency, administration time, indication, signature, name and contact details. A total of 1877 medication prescriptions were reviewed. 1653 prescriptions (88.07%) had no contact number, 1630 (86.84%) did not have an indication, 1230 and 675 (35.96%) used a drug's trade name. Within 261 medication charts, all had at least one entry, which did not include an indication, 258 (98.85%) had at least one entry, which did not have a contact number and 200 (76.63%) had at least one entry, which used a trade name. The introduction of a uniform national medication chart is a positive step, but more needs to be done to address the root causes of prescription error. © 2012 John Wiley & Sons Ltd.

School Uniform Revisited: Procedure, Pressure and Equality

ERIC Educational Resources Information Center

Carney, Damian; Sinclair, Adele

2006-01-01

The House of Lords' decision in "R. (on the application of Begum) v. The Headteacher and Governors of Denbigh High School" considered whether a particular school uniform policy infringed a student's right to manifest her religion under Article 9. This paper analyses the content of this decision, and explores how schools should approach…

21 CFR 1403.12 - Special grant or subgrant conditions for “high-risk” grantees.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Special grant or subgrant conditions for âhigh-riskâ grantees. 1403.12 Section 1403.12 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM...) Has a history of unsatisfactory performance, or (2) Is not financially stable, or (3) Has a management...

21 CFR 1403.12 - Special grant or subgrant conditions for “high-risk” grantees.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Special grant or subgrant conditions for âhigh-riskâ grantees. 1403.12 Section 1403.12 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM...) Has a history of unsatisfactory performance, or (2) Is not financially stable, or (3) Has a management...

21 CFR 1403.12 - Special grant or subgrant conditions for “high-risk” grantees.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Special grant or subgrant conditions for âhigh-riskâ grantees. 1403.12 Section 1403.12 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM...) Has a history of unsatisfactory performance, or (2) Is not financially stable, or (3) Has a management...

21 CFR 1403.12 - Special grant or subgrant conditions for “high-risk” grantees.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Special grant or subgrant conditions for âhigh-riskâ grantees. 1403.12 Section 1403.12 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM...) Has a history of unsatisfactory performance, or (2) Is not financially stable, or (3) Has a management...

Preparation of uniform-sized multiple emulsions and micro/nano particulates for drug delivery by membrane emulsification.

PubMed

Liu, Wei; Yang, Xiang-Liang; Ho, W S Winston

2011-01-01

Much attention has in recent years been paid to fine applications of drug delivery systems, such as multiple emulsions, micro/nano solid lipid and polymer particles (spheres or capsules). Precise control of particle size and size distribution is especially important in such fine applications. Membrane emulsification can be used to prepare uniform-sized multiple emulsions and micro/nano particulates for drug delivery. It is a promising technique because of the better control of size and size distribution, the mildness of the process, the low energy consumption, easy operation and simple equipment, and amendable for large scale production. This review describes the state of the art of membrane emulsification in the preparation of monodisperse multiple emulsions and micro/nano particulates for drug delivery in recent years. The principles, influence of process parameters, advantages and disadvantages, and applications in preparing different types of drug delivery systems are reviewed. It can be concluded that the membrane emulsification technique in preparing emulsion/particulate products for drug delivery will further expand in the near future in conjunction with more basic investigations on this technique. Copyright © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

PubMed

Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

2014-04-01

Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. Copyright © 2013 Elsevier B.V. All rights reserved.

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

Estimation of content of anti-TB drugs supplied at centres of the Revised National TB Control Programme in Tamil Nadu, India.

PubMed

Ramachandran, Geetha; Chandrasekaran, Vedachalam; Hemanth Kumar, Agibothu Kupparam; Dewan, Puneet; Swaminathan, Soumya; Thomas, Aleyamma

2013-09-01

To determine the content of certain antituberculosis (TB) drugs supplied at TB treatment centres of the Revised National TB Control Programme (RNTCP) in the state of Tamil Nadu, India. Eight districts across the state were selected, and the following drugs were collected from five settings (District TB centre, TB unit, designated microscopy centres, DOT providers) in each district: rifampicin (150 and 450 mg), isoniazid (300 mg), pyrazinamide (500 and 750 mg), ethambutol (400 and 600 mg), ethionamide (250 mg), levofloxacin (500 mg) and cycloserine (250 mg). A maximum of 10 tablets/capsules were collected from each setting. The drugs were coded prior to analysis. All drugs were assayed by validated spectrophotometric methods. The acceptable limits for drug content were taken as 90-110% of the stated content. More than 90% of tablets of rifampicin 450 mg, isoniazid 300 mg, pyrazinamide 500 and 750 mg, ethambutol 400 and 600 mg and ethionamide 250 mg were within acceptable limits. Eighty per cent of rifampicin 150 mg, 21% of cycloserine 250 mg and 87% of levofloxacin 500 mg were within acceptable limits. The mean cycloserine content was below the acceptable limit in all districts, the mean drug content being 200 mg (range: 108-245 mg). This systematic study showed that the stated drug content of cycloserine was not reached in all districts. Deterioration of cycloserine could be minimised by storing the drug in refrigerators. The geographical location of the districts had no influence on the drug content. © 2013 John Wiley & Sons Ltd.

Developing drug formularies for the "National Medical Holding" JSC.

PubMed

Akhmadyar, N S; Khairulin, B E; Amangeldy-Kyzy, S; Ospanov, M A

2015-01-01

One of the main problems of drug provision of multidisciplinary hospitals is the necessity to improve the efficiency of budget spending. Despite the efforts undertaken in Kazakhstan for improving the mechanism of drug distribution (creation of the Kazakhstan National Formulary, Unified National Health System, the handbook of medicines (drugs) costs in the electronic register of inpatients (ERI), having a single distributor), the number of unresolved issues still remain."National Medical Holding" JSC (NMH) was established in 2008 and unites 6 innovational healthcare facilities with up to 1431 beds (700 children and 731 adults), located in the medical cluster - which are "National Research Center for Maternal and Child Health" JSC (NRCMC), "Republic Children's Rehabilitation Center" JSC (RCRC), "Republican Diagnostic Center" JSC (RDC), "National Centre for Neurosurgery" JSC (NCN), "National Research Center for Oncology and Transplantation" JSC (NRCOT) and "National Research Cardiac Surgery Center" JSC (NRCSC). The main purpose of NMH is to create an internationally competitive "Hospital of the Future", which will provide the citizens of Kazakhstan and others with a wide range of medical services based on advanced medical technology, modern hospital management, international quality and safety standards. These services include emergency care, outpatient diagnostic services, obstetrics and gynecology, neonatal care, internal medicine, neurosurgery, cardiac surgery, transplantation, cancer care for children and adults, as well as rehabilitation treatment. To create a program of development of a drug formulary of NMH and its subsidiaries. In order to create drug formularies of NMH, analytical, software and statistical methods were used.AII subsidiary organizations of NMH (5 out of 6) except for the NRCOT have been accredited by Joint Commission International (JCI) standards, which ensure the safety of patients and clinical staff, by improving the technological infrastructure, management systems, production environments, and developing program for medications management and use (MMU), etc.MMU is the Chapter 7 of the 5th edition of the standard JCI [1] which is an up-to-date recognized international standard for hospital drug supply and includes 7 points of medication management lifecycle for inpatient hospitals: drug management and organization; selection and procurement; storage; prescription; preparation and distribution; administering medications; monitoring.Due to the developed MMU program of subsidiary organizations the drug provision system was rationalized, starting from defining the individual therapy of a patient and ending with the drug procurement strategy. The practical activity was introduced to the use of drugs committeees with reliable evidence-based performance with obligatory consideration of cost-benefit analysis for each diagnosis-related group. Pre-collected applications for drugs for the year 2015 were submitted in a uniform format in accordance with the structure of the Republican form of the drug [2]. In view of the evidence-base physicians-clinical pharmacologists performed discussions and review of 851 drugs included on the uniform format of the list. Totally 51 (6%) positions were excluded from the list; it was suggested that the format of the application for Paracetamol and Ibuprofen in injectable form be revised; the committee revised the sections on the list for "Antianaemia drugs", iron preparations and methods of prevention of venous thromboembolism with oral anticoagulants.On the basis of this work, the new format, consisting of 449 international nonproprietary names was developed, representing 795 positions with pediatric formulations. In view of the exisitng data and the move to bring to the common standards and uniformity prices of drugs purchased for 2016, the NMH program of clinical pharmacology content with on-line and open access to physicians was created. Within 60 days the DSCHC work was carried out with consultations, selection, definition of requirements of generic and therapeutic substitution. Summing up, drug applications for 2016 with dosage forms include 802 positions and the total bid in monetary terms was by 4,7% lower than in 2015.For the establishment of NMH rational and balanced system of medicine provision to patients and in order to increase availability of quality, safe and effective drugs, we need to have an open and transparent program of the MMU, developed in accordance with the standards of JCI, with the NMH drug formulary, indicating the reference price values of the lower units (tablet, capsule, ampoule, vial, etc.), including the drug lists for a single distributor.To improve drug supply of the NMH DSCHC we have to further cooperation with clinical pharmacologists for the rational use of medicines, guided by the principles of evidence-based medicine.

Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol

PubMed Central

Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed AS

2016-01-01

Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17–99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of −2.24 to −15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities for resveratrol delivery. PMID:26792979

Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

PubMed

Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed As

2016-01-01

Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities for resveratrol delivery.

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

A Model Relating the Uniform Chart of Accounts to Major Disease Categories

DTIC Science & Technology

1985-10-01

THERAPEUTIC ABORTION BOARD - -.- N NURSE MIDWIFERY * . , ,, PSYCHIATRY & NEUROLOGY P PSYCHIATRY , P ADULT _ P ADOLESCENT - P ALCOHOL/ DRUG OTOXIFICATION X P...Substance Induced Organic Disorders MDC 21: Injury, Poisoning, and Toxic Effects of Drugs MDC 22: Burns MDC 23: Selected Factors Influencing Health

Social Work and the Uniform Accident and Sickness Policy Provision Law: A Pilot Project

ERIC Educational Resources Information Center

Cochran, Gerald; Davis, King

2012-01-01

The Uniform Accident and Sickness Policy Provision Law (UPPL) is a statute existing in 26 states that permits health insurance companies to deny payment for claims made by individuals who have sustained injuries as a result of drug or alcohol use. This law presents a series of complicated clinical and ethical dilemmas for social workers and other…

Preparation and in vitro/in vivo evaluation of antimicrobial ocular in situ gels containing a disappearing preservative for topical treatment of bacterial conjunctivitis.

PubMed

Saher, Osama; Ghorab, Dalia M; Mursi, Nadia M

2016-08-01

The study aimed to formulate and evaluate levofloxacin hemihydrate ocular in situ gels along with freshly prepared disappearing preservative reported to be safer to human eyes. Formulae were prepared using thermosensitive (PF127 and PF68) or ion-activated (Gelrite) polymers. They were evaluated for gelation temperature (GT), capacity, content uniformity, pH, rheological behavior, in vitro drug release with kinetic analysis. Best formulae were exposed to storage effect to select the optimum formula that was subjected to different sterilization methods and in vivo evaluation. The prepared disappearing preservative (sodium perborate monohydrate) proved to be active oxidative preservative and compatible with our formulae. F9 (24% PF127, 15% PF 68, 0.5% levofloxacin hemihydrate, and 0.0025% sodium perborate monohydrate) showed prolonged drug release (12 h), acceptable GT, viscosity, and pH. It remained stable over 3 months at two temperatures and was best sterilized by filtration. It showed longer residence time (12 h) in rabbits' eye fluids compared with the Levoxin® eye drops (4 h). This successful attempt of using thermo-gelling system along with a disappearing type of preservatives would allow the use of these systems to achieve sustained release of antimicrobial drugs with minimum risk of eye damage improving patient compliance and treatment efficacy.

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

PubMed Central

Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

2013-01-01

Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated “free” drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. PMID:23769419

Quality assessment of internet pharmaceutical products using traditional and non-traditional analytical techniques.

PubMed

Westenberger, Benjamin J; Ellison, Christopher D; Fussner, Andrew S; Jenney, Susan; Kolinski, Richard E; Lipe, Terra G; Lyon, Robbe C; Moore, Terry W; Revelle, Larry K; Smith, Anjanette P; Spencer, John A; Story, Kimberly D; Toler, Duckhee Y; Wokovich, Anna M; Buhse, Lucinda F

2005-12-08

This work investigated the use of non-traditional analytical methods to evaluate the quality of a variety of pharmaceutical products purchased via internet sites from foreign sources and compared the results with those obtained from conventional quality assurance methods. Traditional analytical techniques employing HPLC for potency, content uniformity, chromatographic purity and drug release profiles were used to evaluate the quality of five selected drug products (fluoxetine hydrochloride, levothyroxine sodium, metformin hydrochloride, phenytoin sodium, and warfarin sodium). Non-traditional techniques, such as near infrared spectroscopy (NIR), NIR imaging and thermogravimetric analysis (TGA), were employed to verify the results and investigate their potential as alternative testing methods. Two of 20 samples failed USP monographs for quality attributes. The additional analytical methods found 11 of 20 samples had different formulations when compared to the U.S. product. Seven of the 20 samples arrived in questionable containers, and 19 of 20 had incomplete labeling. Only 1 of the 20 samples had final packaging similar to the U.S. products. The non-traditional techniques complemented the traditional techniques used and highlighted additional quality issues for the products tested. For example, these methods detected suspect manufacturing issues (such as blending), which were not evident from traditional testing alone.

A New Improved RP-HPLC Method for Assay of Rosuvastatin Calcium in Tablets

PubMed Central

Kaila, H. O.; Ambasana, M. A.; Thakkar, R. S.; Saravaia, H. T.; Shah, A. K.

2010-01-01

A reliable and sensitive isocratic stability indicating RP-HPLC method has been developed and validated for assay of rosuvastatin calcium in tablets and for determination of content uniformity. An isocratic separation of rosuvastatin calcium was achieved on YMC C8, 150×4.6 mm i.d., 5 μm particle size columns with a flow rate of 1.5 ml/min and using a photodiode array detector to monitor the eluate at 242 nm. The mobile phase consisted of acetonitrile: water (40:60, v/v) pH 3.5 adjusted with phosphoric acid. The drug was subjected to oxidation, hydrolysis, photolysis and thermal degradation. All degradation products in an overall analytical run time of approximately 10 min with the parent compound rosuvastatin eluting at approximately 5.2 min. Response was a linear function of drug concentration in the range of 0.5-80 μg/ml (r2= 0.9993) with a limit of detection and quantification of 0.1 and 0.5 μg/ml respectively. Accuracy (recovery) was between 99.6 and 101.7%. Degradation products resulting from the stress studies did not interfere with the detection of rosuvastatin and the assay is thus stability-indicating. PMID:21694991

Preparation and In vitro Evaluation of Naproxen Suppositories

PubMed Central

Hargoli, S.; Farid, J.; Azarmi, S. H.; Ghanbarzadeh, S.; Zakeri-Milani, P.

2013-01-01

The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository. PMID:24019561

Smokeless tobacco: challenges, products and, cessation.

PubMed

Rankin, K Vendrell; Jones, Daniel L; Benton, Elain

2010-06-01

Tobacco companies continue to develop and aggressively market new products for oral use. Most new products are intended to dissolve in the mouth and swallow rather than spit out the juices. These products effectively circumvent smoke-free policies, decrease tobacco cessation efforts, and create individuals who use both smokeless tobacco (ST) and cigarettes. All ST products contain nicotine, carcinogens, and pose multiple health risks. The cancer and health risks associated with ST use extend well beyond the changes in the oral cavity and the risk of oral cancer. Unlike cigarettes, the contents of ST vary widely by brand and product posing difficulty in the use of the available pharmacotherapy for cessation. Although no uniform guidelines exist for the use of pharmacotherapy for smokeless tobacco cessation, research suggests that use of these drugs is effective. The most important motivator for quitting ST cessation remains in the hands of the dentist.

Random myosin loss along thick-filaments increases myosin attachment time and the proportion of bound myosin heads to mitigate force decline in skeletal muscle

PubMed Central

Tanner, Bertrand C.W.; McNabb, Mark; Palmer, Bradley M.; Toth, Michael J.; Miller, Mark S.

2014-01-01

Diminished skeletal muscle performance with aging, disuse, and disease may be partially attributed to the loss of myofilament proteins. Several laboratories have found a disproportionate loss of myosin protein content relative to other myofilament proteins, but due to methodological limitations, the structural manifestation of this protein loss is unknown. To investigate how variations in myosin content affect ensemble cross-bridge behavior and force production we simulated muscle contraction in the half-sarcomere as myosin was removed either i) uniformly, from the Z-line end of thick-filaments, or ii) randomly, along the length of thick-filaments. Uniform myosin removal decreased force production, showing a slightly steeper force-to-myosin content relationship than the 1:1 relationship that would be expected from the loss of cross-bridges. Random myosin removal also decreased force production, but this decrease was less than observed with uniform myosin loss, largely due to increased myosin attachment time (ton) and fractional cross-bridge binding with random myosin loss. These findings support our prior observations that prolonged ton may augment force production in single fibers with randomly reduced myosin content from chronic heart failure patients. These simulation also illustrate that the pattern of myosin loss along thick-filaments influences ensemble cross-bridge behavior and maintenance of force throughout the sarcomere. PMID:24486373

NASA Glenn Icing Research Tunnel: 2014 Cloud Calibration Procedure and Results

NASA Technical Reports Server (NTRS)

Van Zante, Judith F.; Ide, Robert F.; Steen, Laura E.; Acosta, Waldo J.

2014-01-01

The results of the December 2013 to February 2014 Icing Research Tunnel full icing cloud calibration are presented. The calibration steps included establishing a uniform cloud and conducting drop size and liquid water content calibrations. The goal of the calibration was to develop a uniform cloud, and to generate a transfer function from the inputs of air speed, spray bar atomizing air pressure and water pressure to the outputs of median volumetric drop diameter and liquid water content. This was done for both 14 CFR Parts 25 and 29, Appendix C ('typical' icing) and soon-to-be released Appendix O (supercooled large drop) conditions.

NASA Glenn Icing Research Tunnel: Upgrade and Cloud Calibration

NASA Technical Reports Server (NTRS)

VanZante, Judith Foss; Ide, Robert F.; Steen, Laura E.

2012-01-01

In 2011, NASA Glenn s Icing Research Tunnel underwent a major modification to it s refrigeration plant and heat exchanger. This paper presents the results of the subsequent full cloud calibration. Details of the calibration procedure and results are presented herein. The steps include developing a nozzle transfer map, establishing a uniform cloud, conducting a drop sizing calibration and finally a liquid water content calibration. The goal of the calibration is to develop a uniform cloud, and to build a transfer map from the inputs of air speed, spray bar atomizing air pressure and water pressure to the output of median volumetric droplet diameter and liquid water content.

NASA Glenn Icing Research Tunnel: 2012 Cloud Calibration Procedure and Results

NASA Technical Reports Server (NTRS)

VanZante, Judith Foss; Ide, Robert F.; Steen, Laura E.

2012-01-01

In 2011, NASA Glenn s Icing Research Tunnel underwent a major modification to it s refrigeration plant and heat exchanger. This paper presents the results of the subsequent full cloud calibration. Details of the calibration procedure and results are presented herein. The steps include developing a nozzle transfer map, establishing a uniform cloud, conducting a drop sizing calibration and finally a liquid water content calibration. The goal of the calibration is to develop a uniform cloud, and to build a transfer map from the inputs of air speed, spray bar atomizing air pressure and water pressure to the output of median volumetric droplet diameter and liquid water content.

NASA Glenn Icing Research Tunnel: 2014 and 2015 Cloud Calibration Procedures and Results

NASA Technical Reports Server (NTRS)

Steen, Laura E.; Ide, Robert F.; Van Zante, Judith F.; Acosta, Waldo J.

2015-01-01

This report summarizes the current status of the NASA Glenn Research Center (GRC) Icing Research Tunnel cloud calibration: specifically, the cloud uniformity, liquid water content, and drop-size calibration results from both the January-February 2014 full cloud calibration and the January 2015 interim cloud calibration. Some aspects of the cloud have remained the same as what was reported for the 2014 full calibration, including the cloud uniformity from the Standard nozzles, the drop-size equations for Standard and Mod1 nozzles, and the liquid water content for large-drop conditions. Overall, the tests performed in January 2015 showed good repeatability to 2014, but there is new information to report as well. There have been minor updates to the Mod1 cloud uniformity on the north side of the test section. Also, successful testing with the OAP-230Y has allowed the IRT to re-expand its operating envelopes for large-drop conditions to a maximum median volumetric diameter of 270 microns. Lastly, improvements to the collection-efficiency correction for the SEA multi-wire have resulted in new calibration equations for Standard- and Mod1-nozzle liquid water content.

21 CFR 860.123 - Reclassification petition: Content and form.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Reclassification petition: Content and form. 860.123 Section 860.123 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

High-throughput prediction of tablet weight and trimethoprim content of compound sulfamethoxazole tablets for controlling the uniformity of dosage units by NIR.

PubMed

Dong, Yanhong; Li, Juan; Zhong, Xiaoxiao; Cao, Liya; Luo, Yang; Fan, Qi

2016-04-15

This paper establishes a novel method to simultaneously predict the tablet weight (TW) and trimethoprim (TMP) content of compound sulfamethoxazole tablets (SMZCO) by near infrared (NIR) spectroscopy with partial least squares (PLS) regression for controlling the uniformity of dosage units (UODU). The NIR spectra for 257 samples were measured using the optimized parameter values and pretreated using the optimized chemometric techniques. After the outliers were ignored, two PLS models for predicting TW and TMP content were respectively established by using the selected spectral sub-ranges and the reference values. The TW model reaches the correlation coefficient of calibration (R(c)) 0.9543 and the TMP content model has the R(c) 0.9205. The experimental results indicate that this strategy expands the NIR application in controlling UODU, especially in the high-throughput and rapid analysis of TWs and contents of the compound pharmaceutical tablets, and may be an important complement to the common NIR on-line analytical method for pharmaceutical tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

Phase characteristics of rare earth elements in metallic fuel for a sodium-cooled fast reactor by injection casting

NASA Astrophysics Data System (ADS)

Kuk, Seoung Woo; Kim, Ki Hwan; Kim, Jong Hwan; Song, Hoon; Oh, Seok Jin; Park, Jeong-Yong; Lee, Chan Bock; Youn, Young-Sang; Kim, Jong-Yun

2017-04-01

Uranium-zirconium-rare earth (U-Zr-RE) fuel slugs for a sodium-cooled fast reactor were manufactured using a modified injection casting method, and investigated with respect to their uniformity, distribution, composition, and phase behavior according to RE content. Nd, Ce, Pr, and La were chosen as four representative lanthanide elements because they are considered to be major RE components of fuel ingots after pyroprocessing. Immiscible layers were found on the top layers of the melt-residue commensurate with higher fuel slug RE content. Scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS) data showed that RE elements in the melt-residue were distributed uniformly throughout the fuel slugs. RE element agglomeration did not contaminate the fuel slugs but strongly affected the RE content of the slugs.

Quality of compounded hydrocortisone capsules used in the treatment of children.

PubMed

Neumann, Uta; Burau, Daniela; Spielmann, Sarah; Whitaker, Martin J; Ross, Richard J; Kloft, Charlotte; Blankenstein, Oliver

2017-08-01

Due to the lack of paediatric-licensed formulations, children are often treated with individualized pharmacy-compounded adult medication. An international web-based survey about the types of medication in children with adrenal insufficiency (AI) revealed that the majority of paediatric physicians are using pharmacy-compounded medication to treat children with AI. Observations of loss of therapy control in children with congenital adrenal hyperplasia with compounded hydrocortisone capsules and regained control after prescribing a new hydrocortisone batch led to this 'real world' evaluation of pharmacy-compounded paediatric hydrocortisone capsules. Capsule samples were collected randomly from volunteering parents of treated children suffering from congenital adrenal hyperplasia from all over Germany. Analysis of net mass and hydrocortisone content by high-performance liquid chromatography with ultraviolet (HPLC-UV) detection method was performed based on the European Pharmacopeia. In a total of 61 batches that were sent, 5 batches could not be analysed because of missing dose information, insufficient number of capsules or were not possible to be evaluated. Fifty-six batches containing 1125 capsules were evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass or drug content and additional 3.6% failed because they did not contain the labelled drug. Compounded medication is a possible cause of variation of steroid doses in children with adrenal insufficiency or congenital adrenal hyperplasia, putting these vulnerable patients at risk of poor disease control and adrenal crisis. These data may apply to other individualized compounded oral medication as well, emphasizing the need for development of licensed paediatric formulations approved by regulatory authorities. © 2017 European Society of Endocrinology.

Design, formulation, and evaluation of ginger medicated chewing gum

PubMed Central

Aslani, Abolfazl; Ghannadi, Alireza; Rostami, Farnaz

2016-01-01

Background: Various ginger compounds improve gastrointestinal problems and motion sickness. The main effects of ginger allocate to some phenolics such as gingerols and shogaols that act as their active agents. Chewing gums are among convenient dosage forms which patients prefer due to their advantages. Hence, this study tried to design, formulate, and evaluate ginger chewing gum of favorable taste and texture to avoid motion sickness and have gastro-protective and anti-oxidant effect. Materials and Methods: Dried ginger rhizomes were percolated to extract ginger compounds. Total phenolics were measured in 70% hydro-alcoholic extract of ginger by gallic and tannic acid standards using Folin–Ciocalteu’s reagent. Chewing gums containing 50 mg of concentrated extract were prepared. Content uniformity, weight variation, release pattern, organoleptic, and mechanical properties were evaluated. Results: Phenolic content was measured 61.50 ± 5.27 mg/g and 76.75 ± 5.45 mg/g of concentrated extract as gallic acid and tannic acid equivalents, respectively. Release pattern of formulations with different gum bases and sweeteners demonstrated almost 100% release of drug. Evaluation of organoleptic properties was on 10 healthy volunteers and later prepared formulations exhibited better characteristics. Formulations without any flavorants have higher acceptability. Evaluation of mechanical properties showed higher stiffness of F15. Conclusion: Ginger chewing gum comprises admissible properties to be used as a modern drug delivery system due to its advantageous results in motion sickness. It passed all the specified tests for an acceptable chewing gum. Thus, it may be successfully produced to help GI problems. PMID:27563640

Synthesis of thiolated arabinoxylan and its application as sustained release mucoadhesive film former.

PubMed

Zaman, Muhammad; Hanif, Muhammad; Sultana, Kishwar; Atta-Ur-Rehman

2018-02-08

The present work aimed to synthesize thiolated arabinoxylan (TAX), and to evaluate its mucoadhesive potential. Synthesis of TAX was accomplished by esterification of arabinoxylan (AX) with thioglycolic acid (TGA). The appearance of a characteristic peak at 2516 cm -1 in the FTIR spectrum of TAX, and presence of 6.01 ± 1.03 m moles of thiol per gram of the polymer confirmed successful thiolation of AX. The incorporation of the thiol group considerably promoted mucoadhesive strength of the polymer-viz. 3.99-fold. Moreover, in vivo safety analysis in albino rats revealed TAX to be safe in the concentration range of 750-1000 mg kg -1 body weight. Synthesized TAX was utilized to prepare Tizanidine HCl (TZN HCl) loaded sustained release (SR) mucoadhesive buccal films using a solvent casting technique. Results proved that the prepared films were of uniform thickness, good mechanical strength (with folding endurance >300), acceptable moisture contents (5%-7%) and surface pH (6.23 ± 0.81 to 6.43 ± 0.49) compatible to that of the buccal cavity. Presence of greater that 90% of drug contents indicated the excellent drug loading ability of the prepared films. Results of in vitro dissolution studies and ex vivo permeation studies conducted respectively by USP dissolution apparatus II and Franz diffusion cell indicated that sustained effect of TAX was achieved for 8 h. These results have conclusively proven that TAX has the potential to improve the bioavailability of TZN HCl due to enhanced mucoadhesion in buccal cavity, hence signifying its suitability as a mucoadhesive buccal film former.

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.

Role of cellulose ether polymers on ibuprofen release from matrix tablets.

PubMed

Vueba, M L; Batista de Carvalho, L A E; Veiga, F; Sousa, J J; Pina, Maria Eugénia

2005-08-01

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and beta-cyclodextrin (beta-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE(20 h)), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models-Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.

21 CFR 101.67 - Use of nutrient content claims for butter.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Use of nutrient content claims for butter. 101.67 Section 101.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD LABELING Specific Requirements for Nutrient Content Claims § 101...

21 CFR 101.67 - Use of nutrient content claims for butter.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Use of nutrient content claims for butter. 101.67 Section 101.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD LABELING Specific Requirements for Nutrient Content Claims § 101...

21 CFR 101.67 - Use of nutrient content claims for butter.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Use of nutrient content claims for butter. 101.67 Section 101.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD LABELING Specific Requirements for Nutrient Content Claims § 101...

21 CFR 101.67 - Use of nutrient content claims for butter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Use of nutrient content claims for butter. 101.67 Section 101.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD LABELING Specific Requirements for Nutrient Content Claims § 101...

Hot Melt Extruded and Injection Moulded Dosage Forms: Recent Research and Patents.

PubMed

Major, Ian; McConville, Christopher

2015-01-01

Hot Melt Extrusion (HME) and Injection Moulding (IM) are becoming more prevalent in the drug delivery field due to their continuous nature and advantages over current pharmaceutical manufacturing techniques. Hot melt extrusion (HME) is a process that involves the use of at least one reciprocating screw to force a thermoplastic resin along a heated barrel and through a die, while injection moulding is a forming process were molten polymer is forced at high pressure to enter a mould. HME offers a number of advantages over conventional pharmaceutical manufacturing techniques such as increased solubility and bioavailability of poorly water soluble drugs, a solvent free and continuous process, improved content uniformity and flexibility in manufacture. Injection moulding (IM) has been recognised as a rapid and versatile manufacturing technique, which has the advantages of being a continuous process, which is easily scaled up by the use of larger equipment and moulds. However, despite their advantages and the significant number of publications and patents on HME and IM drug delivery devices there are very few marketed formulations. These marketed products range from oral dosage forms which improve bioavailability and reduce pill burden to vaginal rings which provide long-term controlled release thus improving patient compliance. The patenting strategy for IM and HME seems to be focused towards patenting the finished product, more so than patenting the manufacturing process. This is probably due to the fact that the IM and HME processes have already been patented. HME is a process where raw materials (i.e. polymer, plasticizer, drug etc.) are mixed and pumped along by a rotating screw(s) at elevated temperatures through a die to produce a product of uniform shape. IM is similar to HME except that the raw materials are pushed into a mould which is set at lower temperatures. Interest in the use of HME and IM within the pharmaceutical industry is growing with as steady increase in the number of HME patents being issued and with more than 10 products, ranging from oral dosage forms to implantable devices, currently on the market. Therefore, this review of HME and IM is important to the scientific community to further understand and advance these novel and exciting manufacturing techniques.

Preparation and drug controlled release of porous octyl-dextran microspheres.

PubMed

Hou, Xin; Liu, Yanfei

2015-01-01

In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

DTIC Science & Technology

2014-09-01

the drug molecular transport into the cornea. Intravital laser confocal imaging of the live mouse cornea demonstrating the presence of drug in the...vivo drug release in the mouse cornea by laser confocal fluorescence imaging study revealed that the nanowafers upon instillation on mouse eye were...C) 500nm; (D) 1µm; (E) 1.5µm; and (F) 3µm A B C D E F microscopy (SEM) for the feature integrity and uniformity. The SEM images revealed the presence

21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Requirements on content and format of labeling for human prescription drug and biological products. 201.56 Section 201.56 Food and Drugs FOOD AND DRUG... Contraindications Warnings and Precautions Adverse Reactions Drug Interactions Use in Specific Populations Full...

Vertical movement of adult rusty grain beetles, Cryptolestes ferrugineus, in stored corn and wheat at uniform moisture content

PubMed Central

Jian, Fuji; Jayas, Digvir S.; White, Noel D. G.

2006-01-01

Vertical movement and distribution of Cryptolestes ferrugineus (Coleoptera: Laemophloeidae) adults in stored wheat and corn were studied in small (0.1 x 0.1 x 1 m) and large (0.6 m diameter and 1.12 m high) columns. The adults were introduced at the top, middle, and bottom of the small columns with a uniform moisture content (wheat: 14.5 ± 0.1%, corn 13.5 ± 0.1%, 15.5 ± 0.1%, and 17.5 ± 0.1%) at 27.5 ± 0.5°C. When introduced at different locations, adults showed a similar distribution in stored grain bulk with a uniform temperature and moisture content of 14.5% for wheat or 15.5% for corn. Adults showed downward displacement over 24 h when corn moisture was lower than 15.5%, but they did not show downward displacement when moisture content was 17.5%. The upward or downward movement might partially be caused by a drift effect due to beetles sliding between seeds and the displacement of the adults might be the combined effect of walking and falling during their movement. The hydrophilic behavior plus the drift effect explain why the beetles had a faster downward dispersal in the 13.5% corn than in the 15.5% and 17.5% corn and a slight upward displacement in 17.5% corn because they were more active at the lower moisture contents. Adults had a similar movement and distribution in both the small and large wheat columns. PMID:19537976

Eliminating drug price differentials across government programmes in the USA.

PubMed

Chalkidou, Kalipso; Anderson, Gerard F; Faden, Ruth

2011-01-01

Federal agencies in the USA pay significantly different prices for the same prescription drugs because each agency uses a different approach to derive the payment rate. Because we do not identify any economic rationale or socially accepted moral reasoning that would justify the current level of price variation, we suggest that the federal government should pay a uniform price for each drug. Laws and regulations that give certain federal agencies the ability to earn rebates, use formularies, or permit other special arrangements would need to be eliminated in order to have a single payment rate. This could make some government agencies worse off than others; however, a uniform payment rate would not need to affect beneficiaries' current financial contributions, access to drugs, benefits or overall public expenditures. At the same time, having a single rate would permit the government to adopt a more effective approach to purchasing drugs and send a consistent message to pharmaceutical companies concerning which types of drugs the government wants them to develop for government beneficiaries. How this single price would be derived and how it would compare with the lowest or highest prices currently achieved by government agencies would depend on a variety of policy issues including the government's desire to encourage pharmaceutical research and development and the need to control health care spending.

21 CFR 101.62 - Nutrient content claims for fat, fatty acid, and cholesterol content of foods.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cholesterol content of foods. 101.62 Section 101.62 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Nutrient Content Claims § 101.62 Nutrient content claims for fat, fatty acid, and cholesterol content of foods. (a) General requirements. A claim about the level of fat, fatty acid, and cholesterol in a food...

Controlled Release System for Localized and Sustained Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Rodriguez, Lidia Betsabe

Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is possible to prepare biodegradable microparticles with a uniform size distribution and high drug loading efficiency. However, this could only be achieved with a hybrid system consisting of chitosan matrix interior and then exterior coating of PLGA or PLA. A two layer coating of PLGA 50:50 was shown to be optimal with sustainable controlled drug release for almost 5 days and with 91% of degradation (weight loss) in 8 weeks.

Investigation of the Spatiotemporal Responses of Nanoparticles in Tumor Tissues with a Small-Scale Mathematical Model

PubMed Central

Chou, Cheng-Ying; Huang, Chih-Kang; Lu, Kuo-Wei; Horng, Tzyy-Leng; Lin, Win-Li

2013-01-01

The transport and accumulation of anticancer nanodrugs in tumor tissues are affected by many factors including particle properties, vascular density and leakiness, and interstitial diffusivity. It is important to understand the effects of these factors on the detailed drug distribution in the entire tumor for an effective treatment. In this study, we developed a small-scale mathematical model to systematically study the spatiotemporal responses and accumulative exposures of macromolecular carriers in localized tumor tissues. We chose various dextrans as model carriers and studied the effects of vascular density, permeability, diffusivity, and half-life of dextrans on their spatiotemporal concentration responses and accumulative exposure distribution to tumor cells. The relevant biological parameters were obtained from experimental results previously reported by the Dreher group. The area under concentration-time response curve (AUC) quantified the extent of tissue exposure to a drug and therefore was considered more reliable in assessing the extent of the overall drug exposure than individual concentrations. The results showed that 1) a small macromolecule can penetrate deep into the tumor interstitium and produce a uniform but low spatial distribution of AUC; 2) large macromolecules produce high AUC in the perivascular region, but low AUC in the distal region away from vessels; 3) medium-sized macromolecules produce a relatively uniform and high AUC in the tumor interstitium between two vessels; 4) enhancement of permeability can elevate the level of AUC, but have little effect on its uniformity while enhancement of diffusivity is able to raise the level of AUC and improve its uniformity; 5) a longer half-life can produce a deeper penetration and a higher level of AUC distribution. The numerical results indicate that a long half-life carrier in plasma and a high interstitial diffusivity are the key factors to produce a high and relatively uniform spatial AUC distribution in the interstitium. PMID:23565142

Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.

PubMed

Kannan, Vinayagam; Balabathula, Pavan; Divi, Murali K; Thoma, Laura A; Wood, George C

2015-01-01

The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

21 CFR 211.186 - Master production and control records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Master production and control records. 211.186... Reports § 211.186 Master production and control records. (a) To assure uniformity from batch to batch, master production and control records for each drug product, including each batch size thereof, shall be...

21 CFR 211.186 - Master production and control records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Master production and control records. 211.186... Reports § 211.186 Master production and control records. (a) To assure uniformity from batch to batch, master production and control records for each drug product, including each batch size thereof, shall be...

21 CFR 211.186 - Master production and control records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Master production and control records. 211.186... Reports § 211.186 Master production and control records. (a) To assure uniformity from batch to batch, master production and control records for each drug product, including each batch size thereof, shall be...

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPP improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.

Multifunctional biodegradable polymer nanoparticles with uniform sizes: generation and in vitro anti-melanoma activity

NASA Astrophysics Data System (ADS)

Liang, Ruijing; Wang, Jing; Wu, Xian; Dong, Liyun; Deng, Renhua; Wang, Ke; Sullivan, Martin; Liu, Shanqin; Wu, Min; Tao, Juan; Yang, Xiangliang; Zhu, Jintao

2013-11-01

We present a simple, yet versatile strategy for the fabrication of uniform biodegradable polymer nanoparticles (NPs) with controllable sizes by a hand-driven membrane-extrusion emulsification approach. The size and size distribution of the NPs can be easily tuned by varying the experimental parameters, including initial polymer concentration, surfactant concentration, number of extrusion passes, membrane pore size, and polymer molecular weight. Moreover, hydrophobic drugs (e.g., paclitaxel (PTX)) and inorganic NPs (e.g., quantum dots (QDs) and magnetic NPs (MNPs)) can be effectively and simultaneously encapsulated into the polymer NPs to form the multifunctional hybrid NPs through this facile route. These PTX-loaded NPs exhibit high encapsulation efficiency and drug loading density as well as excellent drug sustained release performance. As a proof of concept, the A875 cell (melanoma cell line) experiment in vitro, including cellular uptake analysis by fluorescence microscope, cytotoxicity analysis of NPs, and magnetic resonance imaging (MRI) studies, indicates that the PTX-loaded hybrid NPs produced by this technique could be potentially applied as a multifunctional delivery system for drug delivery, bio-imaging, and tumor therapy, including malignant melanoma therapy.

Nanomedicine Drug Delivery across Mucous Membranes

NASA Astrophysics Data System (ADS)

Lancina, Michael George, III

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In truth, drug biodistribuition is highly non-uniform and dependent on a large number of factors. The development of advanced drug delivery systems to control biodistribution can produce significant advances in clinical treatments without the need to discover new therapeutic compounds. This work focuses on a number of nanostructured materials designed to improve drug delivery by direct and efficient transfer of drugs across one of the body's external mucous membranes. Chapter 1 outlines the central concept that unites these studies: nanomaterials and cationic particles can be used to delivery therapeutic compounds across mucous membranes. Special attention is given to dendritic nanoparticles. In chapter 2, uses for dendrimers in ocular drug delivery are presented. The studies are divided into two main groups: topical and injectable formulations. Chapter 3 does not involve dendrimers but instead another cationic particle used in transmembrane drug delivery, chitosan. Next, a dendrimer based nanofiber mat was used to deliver anti-glaucoma drugs in chapter 4. A three week in vivo efficacy trial showed dendrimer nanofiber mats outperformed traditional eye drops in terms of intra-ocular pressure decrease in a normotensive rat model. Finally, we have developed a new dendrimer based anti-glaucoma drug in chapter 5. Collectively, these studies demonstrate some of the potential applications for nanotechnology to improve transmembrane drug delivery. These particles and fibers are able to readily adhere and penetrate across epithelial cell lays. Utilizing these materials to improve drug absorption through these portals has the potential to improve the clinical treatment of wide variety of diseases.

21 CFR 101.54 - Nutrient content claims for “good source,” “high,” “more,” and “high potency.”

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Nutrient content claims for âgood source,â âhigh,â âmore,â and âhigh potency.â 101.54 Section 101.54 Food and Drugs FOOD AND DRUG ADMINISTRATION... Requirements for Nutrient Content Claims § 101.54 Nutrient content claims for “good source,” “high,” “more...

21 CFR 101.54 - Nutrient content claims for “good source,” “high,” “more,” and “high potency.”

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Nutrient content claims for âgood source,â âhigh,â âmore,â and âhigh potency.â 101.54 Section 101.54 Food and Drugs FOOD AND DRUG ADMINISTRATION... Requirements for Nutrient Content Claims § 101.54 Nutrient content claims for “good source,” “high,” “more...

21 CFR 101.54 - Nutrient content claims for “good source,” “high,” “more,” and “high potency.”

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Nutrient content claims for âgood source,â âhigh,â âmore,â and âhigh potency.â 101.54 Section 101.54 Food and Drugs FOOD AND DRUG ADMINISTRATION... Requirements for Nutrient Content Claims § 101.54 Nutrient content claims for “good source,” “high,” “more...

Influence of adsorbents in transdermal matrix patches on the release and the physical state of ethinyl estradiol and levonorgestrel.

PubMed

Schulz, Martin; Fussnegger, Bernhard; Bodmeier, Roland

2011-02-01

The drug release from medium molecular weight polyisobutene patches containing adsorbates (drug content: 0.2% ethinyl estradiol, 1.0% levonorgestrel; adsorbent content: 20%, w/w) increased in the order of no adsorbent

21 CFR 861.7 - Contents of standards.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contents of standards. 861.7 Section 861.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... performance standard established under this part will include such provisions as the Food and Drug...

21 CFR 1310.06 - Content of records and reports.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Content of records and reports. 1310.06 Section 1310.06 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF... records required to be maintained pursuant to the Federal Food and Drug Administration regulations...

21 CFR 1310.06 - Content of records and reports.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Content of records and reports. 1310.06 Section 1310.06 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF... records required to be maintained pursuant to the Federal Food and Drug Administration regulations...

21 CFR 1310.06 - Content of records and reports.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Content of records and reports. 1310.06 Section 1310.06 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF... records required to be maintained pursuant to the Federal Food and Drug Administration regulations...

21 CFR 1310.06 - Content of records and reports.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Content of records and reports. 1310.06 Section 1310.06 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF... records required to be maintained pursuant to the Federal Food and Drug Administration regulations...

Prescription Drug Abuse Information in D.A.R.E.

ERIC Educational Resources Information Center

Morris, Melissa C.; Cline, Rebecca J. Welch; Weiler, Robert M.; Broadway, S. Camille

2006-01-01

This investigation was designed to examine prescription drug-related content and learning objectives in Drug Abuse Resistance Education (D.A.R.E.) for upper elementary and middle schools. Specific prescription-drug topics and context associated with content and objectives were coded. The coding system for topics included 126 topics organized…

Application of Geant4 simulation for analysis of soil carbon inelastic neutron scattering measurements

USDA-ARS?s Scientific Manuscript database

Inelastic neutron scattering (INS) was applied to determine soil carbon content. Due to non-uniform soil carbon depth distribution, the correlation between INS signals with some soil carbon content parameter is not obvious; however, a proportionality between INS signals and average carbon weight per...

Registration of ‘AU-1101’ peanut

USDA-ARS?s Scientific Manuscript database

AU-1101’ (Reg. No. CV-xxx, PI 661498) is a large-seeded virginia-type peanut (Arachis hypogaea L. subsp. hypogaea var. hypogaea) with high yield and medium maturity, uniform pod size and shape, high grade, superior shelling characters, low oil content, normal oleic acid content, and good flavor. AU-...

78 FR 12760 - Guidance for Industry on Labeling for Human Prescription Drug and Biological Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

...The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Labeling for Human Prescription Drug and Biological Products--Implementing the PLR Content and Format Requirements.'' This guidance is intended to assist applicants in complying with the content and format requirements of labeling for human prescription drug and biological products. The recommendations in this guidance will help ensure that the labeling is clear; useful; informative; and to the extent possible, consistent in content and format. It will assist applicants in developing labeling for new products, revising existing labeling, and implementing the requirements on content and format of labeling for human prescription drug and biological products (71 FR 3922), which appeared in the Federal Register of January 24, 2006. The rule is commonly referred to as the ``Physician Labeling Rule'' (PLR) because it addresses prescription drug labeling that is used by prescribers and other health care practitioners.

Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies.

PubMed

Sengupta, Soma; Banerjee, Sarita; Sinha, Biswadip; Mukherjee, Biswajit

2016-04-01

Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.

18. Uniform cost accounting in long-term care.

PubMed

Sorensen, J E

1976-05-01

Uniform cost data are essential for managing health services, establishing billing and reimbursement rates, and measuring effectiveness and impact. Although it is especially difficult in the case of long-term health care to develop standard cost accounting procedures because of the varied configurations of inpatient, intermediate, and ambulatory services, the overall approaches to cost accounting and its content can be made more uniform. With this purpose in mind, a general model of cost accounting is presented for a multilevel program of long-term services, together with a special method for ambulatory services using "hours accounted for" as the basic measure.

[Study of blending method for the extracts of herbal plants].

PubMed

Liu, Yongsuo; Cao, Min; Chen, Yuying; Hu, Yuzhu; Wang, Yiming; Luo, Guoan

2006-03-01

The irregularity in herbal plant composition is influenced by multiple factors. As for quality control of traditional Chinese medicine, the most critical challenge is to ensure the dosage content uniformity. This content uniformity can be improved by blending different batches of the extracts of herbal plants. Nonlinear least-squares regression was used to calculate the blending coefficient, which means no great absolute differences allowed for all ingredients. For traditional Chinese medicines, even relatively smaller differences could present to be very important for all the ingredients. The auto-scaling pretreatment was used prior to the calculation of the blending coefficients. The pretreatment buffered the characteristics of individual data for the ingredients in different batches, so an improved auto-scaling pretreatment method was proposed. With the improved auto-scaling pretreatment, the relative. differences decreased after blending different batches of extracts of herbal plants according to the reference samples. And the content uniformity control of the specific ingredients could be achieved by the error control coefficient. In the studies for the extracts of fructus gardeniae, the relative differences of all the ingredients is less than 3% after blending different batches of the extracts. The results showed that nonlinear least-squares regression can be used to calculate the blending coefficient of the herbal plant extracts.

21 CFR 209.10 - Content and format of the side effects statement.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Content and format of the side effects statement. 209.10 Section 209.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO DISTRIBUTE A...

21 CFR 209.10 - Content and format of the side effects statement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Content and format of the side effects statement. 209.10 Section 209.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO DISTRIBUTE A...

21 CFR 209.10 - Content and format of the side effects statement.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Content and format of the side effects statement. 209.10 Section 209.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO DISTRIBUTE A...

21 CFR 209.10 - Content and format of the side effects statement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Content and format of the side effects statement. 209.10 Section 209.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO DISTRIBUTE A...

21 CFR 209.10 - Content and format of the side effects statement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Content and format of the side effects statement. 209.10 Section 209.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO DISTRIBUTE A...

The quality of online antidepressant drug information: an evaluation of English and Finnish language Web sites.

PubMed

Prusti, Marjo; Lehtineva, Susanna; Pohjanoksa-Mäntylä, Marika; Bell, J Simon

2012-01-01

The Internet is a frequently used source of drug information, including among people with mental disorders. Online drug information may be narrow in scope, incomplete, and contain errors of omission. To evaluate the quality of online antidepressant drug information in English and Finnish. Forty Web sites were identified using the search terms antidepressants and masennuslääkkeet in English and Finnish, respectively. Included Web sites (14 English, 8 Finnish) were evaluated for aesthetics, interactivity, content coverage, and content correctness using published criteria. All Web sites were assessed using the Date, Author, References, Type, Sponsor (DARTS) and DISCERN quality assessment tools. English and Finnish Web sites had similar aesthetics, content coverage, and content correctness scores. English Web sites were more interactive than Finnish Web sites (P<.05). Overall, adverse drug reactions were covered on 21 of 22 Web sites; however, drug-alcohol interactions were addressed on only 9 of 22 Web sites, and dose was addressed on only 6 of 22 Web sites. Few (2/22 Web sites) provided incorrect information. The DISCERN score was significantly correlated with content coverage (r=0.670, P<.01), content correctness (r=0.663, P<.01), and the DARTS score (r=0.459, P<.05). No Web site provided information about all aspects of antidepressant treatment. Nevertheless, few Web sites provided incorrect information. Both English and Finnish Web sites were similar in terms of aesthetics, content coverage, and content correctness. Copyright © 2012 Elsevier Inc. All rights reserved.

Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing.

PubMed

Li, Qijun; Guan, Xiaoying; Cui, Mengsuo; Zhu, Zhihong; Chen, Kai; Wen, Haoyang; Jia, Danyang; Hou, Jian; Xu, Wenting; Yang, Xinggang; Pan, Weisan

2018-01-15

Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8h floating process with traditional pharmaceutical excipients and lattice internal structure design. Copyright © 2017. Published by Elsevier B.V.

Influence of the aqueous film coating process on the properties and stability of tablets containing a moisture-labile drug.

PubMed

Ruotsalainen, Mirja; Heinämäki, Jyrki; Taipale, Krista; Yliruusi, Jouko

2003-01-01

The effects of an aqueous film coating process on the morphology and storage stability of hydroxypropyl methylcellulose-coated tablets containing a moisture-labile model drug (acetylsalicylic acid, ASA) were evaluated using an instrumented side-vented tablet pan coater. Coating parameters studied were inlet air absolute humidity 5 g/m3 and 12 g/m3, spraying air pressure 100 kPa and 500 kPa, pan air temperature 35 degrees C and 55 degrees C, and coating solution flow rate 2.2 g/min and 7.8 g/min. The surface roughness of the coatings was measured with a laser profilometer and the chemical hydrolysis of the model drug ASA with an UV-spectrophotometer. The film-coated tablets were stored at 25 degrees C/60% RH and 40 degrees C/75% RH for three months. The high absolute humidity of the inlet air increased the residual water content and surface roughness of the coated tablets. Using a lower coating solution flow rate, higher spraying air pressure and pan temperature the coatings were smooth and homogeneous. In both ambient and accelerated storage conditions, the roughness of the coatings and the hydrolysis of ASA increased, but this was independent of the film coating process. Uniform and smooth hydroxypropyl methylcellulose coatings can be achieved by improved control of process parameters related to the application of the coating solution and water evaporation of the tablet surface.

Development of drug-loaded polymer microcapsules for treatment of epilepsy.

PubMed

Chen, Yu; Gu, Qi; Yue, Zhilian; Crook, Jeremy M; Moulton, Simon E; Cook, Mark J; Wallace, Gordon G

2017-09-26

Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles. Here we report the development of fibre- and sphere-based microcapsules that exhibit controllable uniform morphologies and drug release profiles as predicted by mathematical modelling. Importantly, both forms of fabricated microcapsules are compatible with human brain derived neural stem cells and differentiated neurons and neuroglia, indicating clinical compliance for neural implantation and therapeutic drug delivery.

Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier.

PubMed

Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

2017-01-01

In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma.

12 CFR 747.18 - Commencement of proceeding and contents of notice.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INVESTIGATIONS Uniform Rules of Practice and Procedure § 747.18 Commencement of proceeding and contents of notice... given to any other appropriate financial institution supervisory authority where required by law. (3... of the matters of fact or law showing that the NCUA is entitled to relief; (3) A proposed order or...

The Influence of Linguistic Content on the Lombard Effect

ERIC Educational Resources Information Center

Patel, Rupal; Schell, Kevin W.

2008-01-01

Purpose: The "Lombard effect" describes the tendency for speakers to increase pitch, intensity, and duration in the presence of noise. It is unclear whether these modifications are uniformly applied across all words within an utterance or whether information-bearing content words are further enhanced compared with function words. In the present…

A New Method for Determining Permethrin Level on Military Uniform Fabrics

DTIC Science & Technology

2017-06-01

new desorption- gas chromatography–mass spectrometry based screening tool for permethrin content in military fabrics was developed. The method allows...SUBJECT TERMS permethrin, Army Combat Uniform, ACU, camouflage, desorption- gas chromatography-mass spectrometry, D-GC-MS 16. SECURITY CLASSIFICATION OF...and the permethrin contained in the specimens is extracted with solvent with a recovery rate of at least 95%. Samples are analyzed using a gas

Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method.

PubMed

Nah, J W; Paek, Y W; Jeong, Y I; Kim, D W; Cho, C S; Kim, S H; Kim, M Y

1998-08-01

Aim of this work is to prepare poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by dialysis method without surfactant and to investigate drug loading capacity and drug release. The size of PLGA nanoparticles was 269.9 +/- 118.7 nm in intensity average and the morphology of PLGA nanoparticles was spherical shape from the observation of SEM and TEM. In the effect of drug loading contents on the particle size distribution, PLGA nanoparticles were monomodal pattern with narrow size distribution in the empty and lower drug loading nanoparticles whereas bi- or trimodal pattern was showed in the higher drug loading ones. Release of clonazepam from PLGA nanoparticles with higher drug loading contents was slower than that with lower loading contents.

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

Microencapsulation Approach for Orally Extended Delivery of Glipizide: In vitro and in vivo Evaluation

PubMed Central

Abdelbary, A.; El-gendy, N. A.; Hosny, A.

2012-01-01

Glipizide is an effective antidiabetic agent, however, it suffers from relatively short biological half-life. To solve this encumbrance, it is a prospective candidate for fabricating glipizide extended release microcapsules. Microencapsulation of glipizde with a coat of alginate alone or in combination with chitosan or carbomer 934P was prepared employing ionotropic gelation process. The prepared microcapsules were evaluated in vitro by microscopical examination, determination of the particle size, yield and microencapsulation efficiency. The filled capsules were assessed for content uniformity and drug release characteristics. Stability study of the optimised formulas was carried out at three different temperatures over 12 weeks. In vivo bioavailability study and hypoglycemic activity of C9 microcapsules were done on albino rabbits. All formulas achieved high yield, microencapsulation efficiency and extended t1/2. C9 and C19 microcapsules attained the most optimised results in all tests and complied with the dissolution requirements for extended release dosage forms. These two formulas were selected for stability studies. C9 exhibited longer shelf-life and hence was chosen for in vivo studies. C9 microcapsules showed an improvement in the drug bioavailability and significant hypoglycemic activity compared to immediate release tablets (Minidiab® 5 mg). The optimised microcapsule formulation developed was found to produce extended antidiabetic activity. PMID:23626387

Fabrication of Progesterone-Loaded Nanofibers for the Drug Delivery Applications in Bovine

NASA Astrophysics Data System (ADS)

Karuppannan, Chitra; Sivaraj, Mehnath; Kumar, J. Ganesh; Seerangan, Rangasamy; Balasubramanian, S.; Gopal, Dhinakar Raj

2017-02-01

Progesterone is a potent drug for synchronization of the estrus and ovulation cycles in bovine. At present, the estrus cycle of bovine is controlled by the insertion of progesterone-embedded silicone bands. The disadvantage of nondegradable polymer inserts is to require for disposal of these bands after their use. The study currently focuses on preparation of biodegradable progesterone-incorporated nanofiber for estrus synchronization. Three different concentrations (1.2, 1.9, and 2.5 g) of progesterone-impregnated nanofibers were fabricated using electrospinning. The spun membrane were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Uniform surface morphology, narrow size distribution, and interaction between progesterone and zein were confirmed by SEM. FTIR spectroscopy indicated miscibility and interaction between zein and progesterone. X-ray analysis indicated that the size of zein crystallites increased with progesterone content in nanofibers. Significant differences in thermal behavior of progesterone-impregnated nanofiber were observed by DSC. Cell viability studies of progesterone-loaded nanofiber were examined using MTT assay. In vitro release experiment is to identify the suitable progesterone concentration for estrus synchronization. This study confirms that progesterone-impregnated nanofibers are an ideal vehicle for progesterone delivery for estrus synchronization of bovines.

Design, Formulation and Evaluation of an Oral Gel from Punica Granatum Flower Extract for the Treatment of Recurrent Aphthous Stomatitis

PubMed Central

Aslani, Abolfazl; Zolfaghari, Behzad; Davoodvandi, Fatemeh

2016-01-01

Purpose: Recurrent aphthous stomatitis is a disease with unknown etiology that’s mostly treated symptomatically and has no definite cure. Pomegranate (Punica granatum) flowers have been used as medicinal herb that due to its antimicrobial, antioxidant, anti-inflammatory, analgesic and healing effects, has been useful in treatment of oral aphthous. Therefore, we decided to formulate a mucoadhesive gel with pomegranate flower extract to reduce the need for corticosteroid therapy in patients. Methods: Pomegranate flowers are extracted by percolation method. Several formulations with different amounts of carbomer 934, sodium carboxymethylcellulose (SCMC) and hydroxypropyl methylcellulose K4M were prepared and the condensed extract was dispersed in polyethyleneglycol (PEG) 400 and added to gel bases. Then the formulations underwent macroscopic and microscopic studies. The formulations that passed these tests successfully were studied through assay tests using spectrophotometry in 765 nm, drug release from mucoadhesive gel using cell diffusion method, viscosity test, mucoadhesion test and accelerated stability test. Results: The phenolic content of pomegranate flower dried extract was found to be 212.3±1.4 mg/g in dried extract. The F4–F6 formulations contains carbomer 934, SCMC, pomegranate flower extract, PEG 400, potassium sorbate and purified water passed all above tests. Conclusion: The F4 formulation had higher viscosity and mucoadhesion values due to its higher carbomer 934 and SCMC content. Since F4, F5 and F6 had no significant variation in drug release, the F4 formulation was chosen as the superior formulation because of proper appearance and uniformity, acceptable viscosity, mucoadhesion and stability in different temperatures. PMID:27766223

[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.

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...

A colloidal assembly approach to synthesize magnetic porous composite nanoclusters for efficient protein adsorption

NASA Astrophysics Data System (ADS)

Yang, Qi; Lan, Fang; Yi, Qiangying; Wu, Yao; Gu, Zhongwei

2015-10-01

A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation.A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c5nr05800g

A setup for active neutron analysis of the fissile material content in fuel assemblies of nuclear reactors

NASA Astrophysics Data System (ADS)

Bushuev, A. V.; Kozhin, A. F.; Aleeva, T. B.; Zubarev, V. N.; Petrova, E. V.; Smirnov, V. E.

2016-12-01

An active neutron method for measuring the residual mass of 235U in spent fuel assemblies (FAs) of the IRT MEPhI research reactor is presented. The special measuring stand design and uniform irradiation of the fuel with neutrons along the entire length of the active part of the FA provide high accuracy of determination of the residual 235U content. AmLi neutron sources yield a higher effect/background ratio than other types of sources and do not induce the fission of 238U. The proposed method of transfer of the isotope source in accordance with a given algorithm may be used in experiments where the studied object needs to be irradiated with a uniform fluence.

A microfluidic distribution system for an array of hollow microneedles

NASA Astrophysics Data System (ADS)

Hoel, Antonin; Baron, Nolwenn; Cabodevila, Gonzalo; Jullien, Marie-Caroline

2008-06-01

We report a microfluidic device able to control the ejection of fluid through a matrix of out-of-plane microneedles. The device comprises a matrix of open dispensing units connected to needles and filled by a common filling system. A deformable membrane (e.g. in PDMS) is brought into contact with the dispensing units. Pressure exerted on the deformable membrane closes (and thus individualizes) each dispensing unit and provokes the ejection of the dispensing unit content through the outlets. Sufficient pressure over the deformable membrane ensures that all dispensing units deliver a fixed volume (their content) irrespective of the hydrodynamic pressure outside the dispensing unit outlet. The size of the ensemble matrix of dispensing units, the number of liquid reservoirs, as well as the material can vary depending on the considered application of the device or on the conditions of use. In the present paper, the liquid reservoirs are geometrically identical. The geometrical parameters of the device are optimized to avoid as much dead volume as possible, as it was to handle plasmid DNA solutions which are very expensive. The conception, the fabrication and the experimental results are described in this paper. Our prototype is conceived to inject in a uniform way 10 µl of drug through 100 microneedles distributed over 1 cm2.

Manufacture and Drug Delivery Applications of Silk Nanoparticles.

PubMed

Wongpinyochit, Thidarat; Johnston, Blair F; Seib, F Philipp

2016-10-08

Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles. These nanoparticles are subsequently characterized, drug loaded and explored as a potential anticancer drug delivery system. Briefly, silk cocoons are reverse engineered first by degumming the cocoons, followed by silk dissolution and clean up, to yield an aqueous silk solution. Next, the regenerated silk solution is subjected to nanoprecipitation to yield silk nanoparticles - a simple but powerful method that generates uniform nanoparticles. The silk nanoparticles are characterized according to their size, zeta potential, morphology and stability in aqueous media, as well as their ability to entrap a chemotherapeutic payload and kill human breast cancer cells. Overall, the described methodology yields uniform silk nanoparticles that can be readily explored for a myriad of applications, including their use as a potential nanomedicine.

Novel lectin-modified poly(ethylene-co-vinyl acetate) mucoadhesive nanoparticles of carvedilol: preparation and in vitro optimization using a two-level factorial design.

PubMed

Varshosaz, Jaleh; Moazen, Ellaheh

2014-08-01

Carvedilol used in cardiovascular diseases has systemic bioavailability of 25-35%. The objective of this study was production of lectin-modified poly(ethylene-co-vinyl acetate) (PEVA) as mucoadhesive nanoparticles to enhance low oral bioavailability of carvedilol. Nanoparticles were prepared by the emulsification-solvent evaporation method using a two-level factorial design. The studied variables included the vinyl acetate content of the polymer, drug and polymer content. Surface modification of PEVA nanoparticles with lectin was carried out by the adsorption method and coupling efficiency was determined using the Bradford assay. Mucoadhesion of nanoparticles was studied on mucin. The particle size, polydispersity index, zeta potential, drug loading and drug release from nanoparticles were studied. The morphology of nanoparticles and crystalline status of the entrapped drug were studied by SEM, DSC and XRD tests, respectively. Results showed the most effective factor on particle size and zeta potential was the interaction of polymer and drug content while, drug loading efficiency and mucoadhesion were more affected by the interaction of polymer type and drug content. Drug concentration was the most effective variable on the drug release rate. The drug was in amorphous state in nanoparticles. The optimum nanoparticles obtained by 45 mg of copolymer contained 12% vinyl acetate/4.3 ml of organic phase and drug concentration of 37.5 wt% of polymer.

21 CFR 101.13 - general principles.

Code of Federal Regulations, 2010 CFR

1996-04-01

... content claims FOOD AND DRUGS FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--CONTINUED FOOD FOR HUMAN CONSUMPTION FOOD LABELING General Provisions Sec. 101.13 Nutrient content claims... supplements). (b) A claim that expressly or implicitly characterizes the level of a nutrient (nutrient content...

Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

PubMed

Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

2010-09-01

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

Tailoring the mucoadhesive and sustained release characteristics of mesalamine loaded formulations for local treatment of distal forms of ulcerative colitis.

PubMed

Ali, Hany S M; Hanafy, Ahmed F; El Achy, Samar N

2016-10-10

Direct delivery of sustained therapeutic levels of mesalamine (MS) via rectal systems to manage distal forms of ulcerative colitis was studied. The High molecular weight hydroxypropyl methylcellulose (HPMC K4M) polymer was combined with hydrophilic surfactants to control polymer hydration process allowing optimization of the mucoadhesive and controlled drug release properties for the rectal systems. Physical mixtures and granules of MS and HPMC K4M were prepared and in vitro characterized using scanning electron microscope, differential scanning calorimetry and X-ray diffraction techniques. Rectal formulations were prepared utilizing MS-HPMC K4M mixtures in different polyethylene glycol (PEG) combination bases. The developed rectal formulations were investigated for physical, mucoadhesion, in-vitro drug release and swelling characteristics. Results revealed acceptable physical characteristics of the prepared formulations with good content uniformity and minimum weight variation. Sustained release patterns of MS form HPMC K4M based formulations were observed. Formulations prepared using high proportions of the polymer or PEG 400 showed higher extent of mucoadhesion, swelling and greatly extended drug release time. Efficacy of an optimized formulation was assessed using the acetic acid induced colitis model in rats and compared to a reference polymer-free formulation of the drug. Clinical evaluation included bleeding from rectum, consistency of animal stool and colon/body weight ratio. Furthermore, histopathological analysis was carried out to evaluate the degree of inflammation and mucosal damage. Overall results showed a significant enhancement in the clinical pictures and colon histopathology of animals treated by the sustained release mucoadhesive formulation compared to the reference polymer free formulation and the non-treated colitis group. Copyright © 2016 Elsevier B.V. All rights reserved.

In Situ Real-Time Radiographic Study of Thin Film Formation Inside Rotating Hollow Spheres

DOE PAGES

Braun, Tom; Walton, Christopher C.; Dawedeit, Christoph; ...

2016-02-03

The hollow spheres with uniform coatings on the inner surface have applications in optical devices, time- or site-controlled drug release, heat storage devices, and target fabrication for inertial confinement fusion experiments. The fabrication of uniform coatings, which is often critical for the application performance, requires precise understanding and control over the coating process and its parameters. We report on in situ real-time radiography experiments that provide critical spatiotemporal information about the distribution of fluids inside hollow spheres during uniaxial rotation. Furthermore, image analysis and computer fluid dynamics simulations were used to explore the effect of liquid viscosity and rotational velocitymore » on the film uniformity. The data were then used to demonstrate the fabrication of uniform sol–gel chemistry derived porous polymer films inside 2 mm inner diameter diamond shells.« less

In Situ Real-Time Radiographic Study of Thin Film Formation Inside Rotating Hollow Spheres

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

Braun, Tom; Walton, Christopher C.; Dawedeit, Christoph

2016-02-03

Hollow spheres with uniform coatings on the inner surface have applications in optical devices, time- or site controlled drug release, heat storage devices, and target fabrication for inertial confinement fusion experiments. The fabrication of uniform coatings, which is often critical for the application performance, requires precise understanding and control over the coating process and its parameters. Here, we report on in-situ real-time radiography experiments that provide critical spatio-temporal information about the distribution of fluids inside hollow spheres during uniaxial rotation. Image analysis and computer fluid dynamics simulations were used to explore the effect of liquid viscosity and rotational velocity onmore » the film uniformity. The data were then used to demonstrate the fabrication of uniform sol-gel chemistry derived porous polymer films inside 2mm inner diameter diamond shells.« less

Selection and Clonal Propagation of High Artemisinin Genotypes of Artemisia annua

PubMed Central

Wetzstein, Hazel Y.; Porter, Justin A.; Janick, Jules; Ferreira, Jorge F. S.; Mutui, Theophilus M.

2018-01-01

Artemisinin, produced in the glandular trichomes of Artemisia annua L. is a vital antimalarial drug effective against Plasmodium falciparum resistant to quinine-derived medicines. Although work has progressed on the semi-synthetic production of artemisinin, field production of A. annua remains the principal commercial source of the compound. Crop production of artemisia must be increased to meet the growing worldwide demand for artemisinin combination therapies (ACTs) to treat malaria. Grower artemisinin yields rely on plants generated from seeds from open-pollinated parents. Although selection has considerably increased plant artemisinin concentration in the past 15 years, seed-generated plants have highly variable artemisinin content that lowers artemisinin yield per hectare. Breeding efforts to produce improved F1 hybrids have been hampered by the inability to produce inbred lines due to self-incompatibility. An approach combining conventional hybridization and selection with clonal propagation of superior genotypes is proposed as a means to enhance crop yield and artemisinin production. Typical seed-propagated artemisia plants produce less than 1% (dry weight) artemisinin with yields below 25 kg/ha. Genotypes were identified producing high artemisinin levels of over 2% and possessing improved agronomic characteristics such as high leaf area and shoot biomass production. Field studies of clonally-propagated high-artemisinin plants verified enhanced plant uniformity and an estimated gross primary productivity of up to 70 kg/ha artemisinin, with a crop density of one plant m-2. Tissue culture and cutting protocols for the mass clonal propagation of A. annua were developed for shoot regeneration, rooting, acclimatization, and field cultivation. Proof of concept studies showed that both tissue culture-regenerated plants and rooted cutting performed better than plants derived from seed in terms of uniformity, yield, and consistently high artemisinin content. Use of this technology to produce plants with homogeneously-high artemisinin can help farmers markedly increase the artemisinin yield per cultivated area. This would lead to increased profit to farmers and decreased prices of ACT. PMID:29636758

Webizing mobile augmented reality content

NASA Astrophysics Data System (ADS)

Ahn, Sangchul; Ko, Heedong; Yoo, Byounghyun

2014-01-01

This paper presents a content structure for building mobile augmented reality (AR) applications in HTML5 to achieve a clean separation of the mobile AR content and the application logic for scaling as on the Web. We propose that the content structure contains the physical world as well as virtual assets for mobile AR applications as document object model (DOM) elements and that their behaviour and user interactions are controlled through DOM events by representing objects and places with a uniform resource identifier. Our content structure enables mobile AR applications to be seamlessly developed as normal HTML documents under the current Web eco-system.

Quantification of Cannabinoid Content in Cannabis

NASA Astrophysics Data System (ADS)

Tian, Y.; Zhang, F.; Jia, K.; Wen, M.; Yuan, Ch.

2015-09-01

Cannabis is an economically important plant that is used in many fields, in addition to being the most commonly consumed illicit drug worldwide. Monitoring the spatial distribution of cannabis cultivation and judging whether it is drug- or fiber-type cannabis is critical for governments and international communities to understand the scale of the illegal drug trade. The aim of this study was to investigate whether the cannabinoids content in cannabis could be spectrally quantified using a spectrometer and to identify the optimal wavebands for quantifying the cannabinoid content. Spectral reflectance data of dried cannabis leaf samples and the cannabis canopy were measured in the laboratory and in the field, respectively. Correlation analysis and the stepwise multivariate regression method were used to select the optimal wavebands for cannabinoid content quantification based on the laboratory-measured spectral data. The results indicated that the delta-9-tetrahydrocannabinol (THC) content in cannabis leaves could be quantified using laboratory-measured spectral reflectance data and that the 695 nm band is the optimal band for THC content quantification. This study provides prerequisite information for designing spectral equipment to enable immediate quantification of THC content in cannabis and to discriminate drug- from fiber-type cannabis based on THC content quantification in the field.

34 CFR 363.5 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

...). (4) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 363. (c) The following...

34 CFR 363.5 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

...). (4) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 363. (c) The following...

34 CFR 363.5 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

...). (4) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 363. (c) The following...

34 CFR 363.5 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

...). (4) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 363. (c) The following...

34 CFR 363.5 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

...). (4) 34 CFR part 80 (Uniform Administrative Requirements for Grants and Cooperative Agreements to... part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 363. (c) The following...

TOC: Table of Contents Practices of Primary Journals--Recommendations for Monolingual, Multilingual and International Journals.

ERIC Educational Resources Information Center

Juhasz, Stephen; And Others

Table of contents (TOC) practices of some 120 primary journals were analyzed. The journals were randomly selected. The method of randomization is described. The samples were selected from a university library with a holding of approximately 12,000 titles published worldwide. A questionnaire was designed. Purpose was to find uniformity and…

An Oil/Water disperser device for use in an oil content Monitor/Control system

NASA Astrophysics Data System (ADS)

Kempel, F. D.

1985-07-01

This patent application discloses an oil content monitor/control unit system, including an oil/water disperser device, which is configured to automatically monitor and control processed effluent from an associated oil/water separator so that if the processed effluent exceeds predetermine in-port or at-sea oil concentration lmits, it is either recirculated to an associated oil/water separator via a ship's bilge for additional processing, or diverted to a holding tank for storage. On the other hand, if the oil concentration of the processed effluent is less than predetermine in-port or at-sea limits, it is discharged overboard. The oil/water disperser device is configured to break up any oil present in the processed effluent into uniform droplets for more accurate sensing of the oil present in the processed effluent into uniform droplets for more accurate sensing of the oil-in-water concentration level thereof. The oil/water disperser device has a flow-actuated variable orifice configured into a spring-loaded polyethylene plunger which provides the uniform distribution of oil droplets.

Comparison of drying characteristic and uniformity of banana cubes dried by pulse-spouted microwave vacuum drying, freeze drying and microwave freeze drying.

PubMed

Jiang, Hao; Zhang, Min; Mujumdar, Arun S; Lim, Rui-Xin

2014-07-01

To overcome the flaws of high energy consumption of freeze drying (FD) and the non-uniform drying of microwave freeze drying (MFD), pulse-spouted microwave vacuum drying (PSMVD) was developed. The results showed that the drying time can be dramatically shortened if microwave was used as the heating source. In this experiment, both MFD and PSMVD could shorten drying time by 50% as compared to the FD process. Depending on the heating method, MFD and PSMVD dried banana cubes showed trends of expansion while FD dried samples demonstrated trends of shrinkage. Shrinkage also brought intensive structure and highest fracturability of all three samples dried by different methods. The residual ascorbic acid content of PSMVD dried samples can be as high as in FD dried samples, which were superior to MFD dried samples. The tests confirmed that PSMVD could bring about better drying uniformity than MFD. Besides, compared with traditional MFD, PSMVD can provide better extrinsic feature, and can bring about improved nutritional features because of the higher residual ascorbic acid content. © 2013 Society of Chemical Industry.

Marathon Group Counseling with Illicit Drug Users: Analysis of Content.

ERIC Educational Resources Information Center

Page, Richard C.; Wills, Judy

1983-01-01

Summarized a 16-hour marathon group for illicit drug users (N=12) in residential treatment. Content analysis showed the group spent more time on interpersonal relationships and relatively little time on group process. Drug users were able to successfully participate in therapeutic group discussions involving self-investment. (JAC)

Producibility of fibrous refractory composite insulation, FRCI 40-20. [for reusable heat shielding

NASA Technical Reports Server (NTRS)

Strauss, E. L.; Johnson, C. W.; Graese, R. W.; Campbell, R. L.

1983-01-01

Fibrous Refractory Composite Insulation (FRCI) is a NASA-developed, second generation, reusable heat-shield material that comprises a mixture of aluminoborosilicate fibers, silica fibers, and silicon carbide. Under NASA contract, a program was conducted to demonstrate the capability for manufacturing FRCI 40-20 billets. A detailed fabrication procedure was written and validated by testing specimens from the first two billets. The material conformed to NASA requirements for density, tensile strength, modulus of rupture, thermal expansion, cristobalite content, and uniformity. Twenty-four billets were prepared to provide 20 deliverable articles. Production billets were checked for density, modulus of rupture, cristobalite content, and uniformity. Billet density ranged from 309.48 to 332.22 kg/cu m (19.32 to 20.74 lb/cu ft) and modulus of rupture from 4690 to 10,140 kPa (680 to 1470 psi). Cristobalite content was less than 1 percent. A Weibull analysis of modulus-of-rupture data indicated a 1.5 percent probability for failure below the specified strength of 4480 kPa (650 psi).

Highly luminescent, high-indium-content InGaN film with uniform composition and full misfit-strain relaxation

NASA Astrophysics Data System (ADS)

Fischer, A. M.; Wei, Y. O.; Ponce, F. A.; Moseley, M.; Gunning, B.; Doolittle, W. A.

2013-09-01

We have studied the properties of thick InxGa1-xN films, with indium content ranging from x ˜ 0.22 to 0.67, grown by metal-modulated epitaxy. While the low indium-content films exhibit high density of stacking faults and dislocations, a significant improvement in the crystalline quality and optical properties has been observed starting at x ˜ 0.6. Surprisingly, the InxGa1-xN film with x ˜ 0.67 exhibits high luminescence intensity, low defect density, and uniform full lattice-mismatch strain relaxation. The efficient strain relaxation is shown to be due to a critical thickness close to the monolayer range. These films were grown at low temperatures (˜400 °C) to facilitate indium incorporation and with precursor modulation to enhance surface morphology and metal adlayer diffusion. These findings should contribute to the development of growth techniques for nitride semiconductors under high lattice misfit conditions.

First Dutch national guidelines--pharmacological care for detained opioid addicts.

PubMed

Arends, M T; De Haan, H A; Van 't Hoff, G I C M

2009-01-01

Heterogenic care of addicted detainees in the various prisons in The Netherlands triggered the National Agency of Correctional Institutions of the Ministry of Justice, to order the Dutch Institute for Health Care Improvement (CBO) to formulate the first national guideline titled 'Pharmacological care for detained addicts'. This article presents the content of this guideline, which mainly focuses on opioid-dependent addicts. In The Netherlands, approximately 50% of the detainees are problematic substance abusers, while again half of this group suffers from psychiatric co-morbidity. In addition, somatic co-morbidity, especially infectious diseases, is also common. Due to the moderate outcome seen with voluntary drug counselling regimes in prison, there is a policy shift to extent utilization of legally enforced approaches. Continuity of care is of great importance. In case of opioid addicts this, in general, means continuation of methadone maintenance treatment. Aftercare immediately after detention and optimalization of medical information transfer is crucial. This guideline aims to realize optimal and uniform management of addiction disorders in the Dutch prison system.

Assessment of the quality of simvastatin capsules from compounding pharmacies.

PubMed

Markman, Blanca Elena Ortega; Rosa, Paulo César Pires; Koschtschak, Maria Regina Walter

2010-12-01

To validate a method for determining the simvastatin content of compounded capsules, using high performance liquid chromatography. Eighteen samples of simvastatin 40 mg capsules from compounding pharmacies in the cities of São Paulo, Guarulhos, São Bernardo do Campo and Campinas, Southeastern Brazil, prescribed for fictitious patients were assessed. The analyses were based on the Brazilian Pharmacopoeia and on the high performance liquid chromatography method, optimized and validated in accordance with national and international standards for identification and quantification tests on compounded capsules. The mean weight of the capsules ranged from 70 mg to 316 mg; four samples presented weight variation outside of the specification. The simvastatin content in the capsules was within the specification in 11 samples. In six, the content ranged from 4% to 87% of the declared quantity, thereby not complying with the content requirements for the active agent. For one sample, no content or uniformity determinations were performed. In the content uniformity test, 15 samples presented indices of less than 85%, with relative standard deviations greater than 6%. Three pharmacies had met the specification in this test. In the dissolution test, eight samples presented unsatisfactory results in the first stage of the test, while the remainder presented inconclusive results. The method used was shown to be suitable for application to quality control, and it revealed the poor quality of the simvastatin capsules produced by some compounding pharmacies.

Pangamic Acid (Vitamin B15, Pangametin, Sopangamine)

PubMed Central

French, W. N.; Levi, Leo

1966-01-01

Pangamic acid is shown to be a mixture of variable composition. Criteria of identity and methods of analysis are described for five pharmaceutical dosage forms. Experimental results indicate that the products are not uniform in composition and that composition does not conform to label claims. No satisfactory preclinical drug application for any such preparation has so far been submitted to the Food and Drug Directorate. PMID:5295884

34 CFR 380.8 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 380. (c...

34 CFR 377.4 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The following regulations in 34 CFR part 369...

34 CFR 377.4 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The following regulations in 34 CFR part 369...

34 CFR 380.8 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 380. (c...

34 CFR 377.4 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The following regulations in 34 CFR part 369...

34 CFR 380.8 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 380. (c...

34 CFR 377.4 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The following regulations in 34 CFR part 369...

34 CFR 377.4 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The following regulations in 34 CFR part 369...

34 CFR 380.8 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 380. (c...

Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

PubMed

Hancock, Bruno C; Ketterhagen, William R

2011-10-14

Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines. Sampling uniformly across the discharge process gave the most accurate results with respect to identifying segregation trends. Sigmoidal sampling (as recommended in the PQRI BUWG guidelines) tended to overestimate potential segregation issues, whereas truncated sampling (common in industrial practice) tended to underestimate them. The size of the sample had a major effect on the absolute potency RSD. The number of sampling locations (10 vs. 20) had very little effect on the trends in the data, and the number of samples analyzed at each location (1 vs. 3 vs. 7) had only a small effect for the sampling conditions examined. The results of this work provide greater understanding of the effect of different sampling approaches on the measured content uniformity of real dosage forms, and can help to guide the choice of appropriate sampling protocols. Copyright © 2011 Elsevier B.V. All rights reserved.

Quantitative spatial distribution of sirolimus and polymers in drug-eluting stents using confocal Raman microscopy.

PubMed

Balss, K M; Llanos, G; Papandreou, G; Maryanoff, C A

2008-04-01

Raman spectroscopy was used to differentiate each component found in the CYPHER Sirolimus-eluting Coronary Stent. The unique spectral features identified for each component were then used to develop three separate calibration curves to describe the solid phase distribution found on drug-polymer coated stents. The calibration curves were obtained by analyzing confocal Raman spectral depth profiles from a set of 16 unique formulations of drug-polymer coatings sprayed onto stents and planar substrates. The sirolimus model was linear from 0 to 100 wt % of drug. The individual polymer calibration curves for poly(ethylene-co-vinyl acetate) [PEVA] and poly(n-butyl methacrylate) [PBMA] were also linear from 0 to 100 wt %. The calibration curves were tested on three independent drug-polymer coated stents. The sirolimus calibration predicted the drug content within 1 wt % of the laboratory assay value. The polymer calibrations predicted the content within 7 wt % of the formulation solution content. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra from five formulations confirmed a linear response to changes in sirolimus and polymer content. Copyright 2007 Wiley Periodicals, Inc.

Rapid analysis of drug dissolution by paper spray ionization mass spectrometry.

PubMed

Liu, Yang; Liu, Ning; Zhou, Ya-Nan; Lin, Lan; He, Lan

2017-03-20

With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs - enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90min to 6min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests. Copyright © 2016 Elsevier B.V. All rights reserved.

Typology of Delivery Quality: Latent Profile Analysis of Teacher Engagement and Delivery Techniques in a School-Based Prevention Intervention, "Keepin' It REAL" Curriculum

ERIC Educational Resources Information Center

Shin, YoungJu; Miller-Day, Michelle; Pettigrew, Jonathan; Hecht, Michael L.; Krieger, Janice L.

2014-01-01

Enhancing the delivery quality of school-based, evidence-based prevention programs is one key to ensuring uniform program effects on student outcomes. Program evaluations often focus on content dosage when implementing prevention curricula, however, less is known about implementation quality of prevention content, especially among teachers who may…

Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier

PubMed Central

Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

2017-01-01

In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma. PMID:28652738

Optimization of a jet-propelled particle injection system for the uniform transdermal delivery of drug/vaccine.

PubMed

Liu, Yi; Kendall, Mark A F

2007-08-01

A jet-propelled particle injection system, the biolistics, has been developed and employed to accelerate micro-particles for transdermal drug delivery. We have examined a prototype biolistic device employing a converging-diverging supersonic nozzle (CDSN), and found that the micro-particles were delivered with a wide velocity range (200-800 m/s) and spatial distribution. To provide a controllable system for transdermal drug delivery, we present a contoured shock-tube (CST) concept and its embodiment device. The CST configuration utilizes a quasi-steady, quasi-one dimensional and shock-free supersonic flow to deliver the micro-particles with an almost uniform velocity (the mean velocity and the standard deviation, 699 +/- 4.7 m/s) and spatial distribution. The transient gas and particle dynamics in both prototype devices are interrogated with the validated computational fluid dynamics (CFD) approach. The predicted results for static pressure and Mach number histories, gas flow structures, particle velocity distributions and gas-particle interactions are presented and interpreted. The implications for clinical uses are discussed. (c) 2007 Wiley Periodicals, Inc.

Co-Prime Frequency and Aperture Design for HF Surveillance, Wideband Radar Imaging, and Nonstationary Array Processing

DTIC Science & Technology

2018-03-01

offset designs . Particularly, the proposed CA-CFO is compared with uniform linear array and uniform frequency offset (ULA-UFO). Uniform linear array...and Aperture Design for HF Surveillance, Wideband Radar Imaging, and Nonstationary Array Processing (Grant No. N00014-13-1-0061) Submitted to...Contents 1. Executive Summary …………………………………………………………………………. 1 1.1. Generalized Co-Prime Array Design ………………………………………………… 1 1.2. Wideband

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%).

PubMed

Marlowe, Zora T; Davio, Stephen R

2014-01-01

Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte®) and a generic prednisolone acetate suspension 1% were used as comparators. Drug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing - consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC) method and reported as a percentage of the declared (labeled) concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity. Mean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD]) percent declared concentration of 102% (1.92%) over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling significantly below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing regimen. Dispersion analysis at 120× g showed no drug particle sedimentation for LE ophthalmic gel over the 24-hour testing period, whereas the prednisolone acetate suspensions settled in less than 6 hours. LE ophthalmic gel 0.5% provided consistent dose uniformity at the declared concentration whether or not the bottle was shaken prior to dispensing, whereas Pred Forte® and the generic prednisolone acetate required shaking to provide consistent drug concentrations. LE ophthalmic gel may be beneficial to patients because it eliminates the potential impact on the clinical response of both under- and overdosing.

34 CFR 369.3 - What regulations apply to these programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Service Program for American Indians with Disabilities. (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 369. (c...

34 CFR 385.3 - What regulations apply to these programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 385. (c) The...

34 CFR 385.3 - What regulations apply to these programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 385. (c) The...

34 CFR 369.3 - What regulations apply to these programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Service Program for American Indians with Disabilities. (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 369. (c...

34 CFR 369.3 - What regulations apply to these programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Service Program for American Indians with Disabilities. (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 369. (c...

34 CFR 369.3 - What regulations apply to these programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Service Program for American Indians with Disabilities. (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 369. (c...

34 CFR 385.3 - What regulations apply to these programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 385. (c) The...

34 CFR 385.3 - What regulations apply to these programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 385. (c) The...

75 FR 21579 - Announcement of Grant Application Deadlines and Funding Levels

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... other source; d. Items bought or built prior to the application deadline specified in this Notice of... precautions; (4) Uniform Relocation Assistance and Real Property Acquisition Policies Act of 1970; (5) Drug...

76 FR 34036 - Announcement of Grant Application Deadlines and Funding Levels

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... have been funded by any other source; d. Items bought or built prior to the application deadline... precautions; (4) Uniform Relocation Assistance and Real Property Acquisition Policies Act of 1970; (5) Drug...

21 CFR 161.30 - Declaration of quantity of contents on labels for canned oysters.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Declaration of quantity of contents on labels for canned oysters. 161.30 Section 161.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FISH AND SHELLFISH General Provisions § 161...

Spatiotemporal Quantification of Local Drug Delivery Using MRI

PubMed Central

Giers, Morgan B.; McLaren, Alex C.; Plasencia, Jonathan D.; McLemore, Ryan; Caplan, Michael R.

2013-01-01

Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery was performed to visualize and quantify the time resolved distribution of MRI contrast agents. Three-dimensional T 1 maps (generated from T 1-weighted images with varied T R) were processed using noise-reducing filtering. A segmented region of contrast, from a thresholded image, was converted to concentration maps using the equation 1/T 1 = 1/T 1,0 + R 1 C, where T 1,0 and T 1 are the precontrast and postcontrast T 1 map values, respectively. In this technique, a uniform estimated value for T 1,0 was used. Error estimations were performed for each step. The practical usefulness of this method was assessed using comparisons between devices located in different locations both with and without contrast. The method using a uniform T 1,0, requiring no registration of pre- and postcontrast image volumes, was compared to a method using either affine or deformation registrations. PMID:23710248

Pharmaceutical companies and their drugs on social media: a content analysis of drug information on popular social media sites.

PubMed

Tyrawski, Jennifer; DeAndrea, David C

2015-06-01

Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies' social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers who interacted with pharmaceutical companies through commenting (23.9%, 177/740). For the drug-specific analysis, we found that the majority of search results contained drug product claims (69.4%, 482/695); more claims mentioned only benefits (44.8%, 216/482) relative to only risks (27.2%, 131/482). Additionally, approximately 25% (150/603) of posts on Twitter and YouTube were presented as personal testimonials. A considerable percentage of content on Facebook contained advertisements for illegal online pharmacies (17%, 16/92). Pharmaceutical companies avoid making drug product claims on their social media accounts but frequently post content that is consistent with FDA definitions for help-seeking DTCA. Thousands of people often view content posted by pharmaceutical companies on social media; users also share company postings making both direct and indirect influence possible. Finally, people are likely to be exposed to drug product claims and information about illegal pharmacies when searching for information about popular pharmaceutical drugs on social media.

Pharmaceutical Companies and Their Drugs on Social Media: A Content Analysis of Drug Information on Popular Social Media Sites

PubMed Central

2015-01-01

Background Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Objective Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Methods Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. Results From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies’ social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers who interacted with pharmaceutical companies through commenting (23.9%, 177/740). For the drug-specific analysis, we found that the majority of search results contained drug product claims (69.4%, 482/695); more claims mentioned only benefits (44.8%, 216/482) relative to only risks (27.2%, 131/482). Additionally, approximately 25% (150/603) of posts on Twitter and YouTube were presented as personal testimonials. A considerable percentage of content on Facebook contained advertisements for illegal online pharmacies (17%, 16/92). Conclusions Pharmaceutical companies avoid making drug product claims on their social media accounts but frequently post content that is consistent with FDA definitions for help-seeking DTCA. Thousands of people often view content posted by pharmaceutical companies on social media; users also share company postings making both direct and indirect influence possible. Finally, people are likely to be exposed to drug product claims and information about illegal pharmacies when searching for information about popular pharmaceutical drugs on social media. PMID:26032738

A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

NASA Astrophysics Data System (ADS)

Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

2015-12-01

Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ~87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

Electromagnetic Fields of a Uniform Sphere in a Uniform Conducting Medium with Application to Dipole Sources

DTIC Science & Technology

1991-09-01

12b. DISTRIBUTION CODE Approved for public release; distribution is unlimited. 13. ABSTRACT (Maximum 200 words) Vector spherical harmonic expansions are...electric and magnetic field vectors from E rand B - r alone. Genural expressions are given relating the scattered field expansion coefficients to the source...Prescnbed by ANSI Std. Z39-18 29W-102 NCSC TR 426-90 CONTENTS Pag o INTRODUCTION 1 BACKGROUND 1 ANGULAR MOMENTUM OPERATOR AND VECTOR SPHERICAL

On the Pressure of a Neutron Gas Interacting with the Non-Uniform Magnetic Field of a Neutron Star

NASA Astrophysics Data System (ADS)

Skobelev, V. V.

2018-04-01

On the basis of simple arguments, practically not going beyond the scope of an undergraduate course in general physics, we estimate the additional pressure (at zero temperature) of degenerate neutron matter due to its interaction with the non-uniform magnetic field of a neutron star. This work has methodological and possibly scientific value as an intuitive application of the content of such a course to a solution of topical problems of astrophysics.

75 FR 13766 - Guidance for Industry on the Content and Format of the Dosage and Administration Section of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

...The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Dosage and Administration Section of Labeling for Human Prescription Drug and Biological Products--Content and Format.'' This guidance is one of a series of guidance documents intended to assist applicants in drafting prescription drug labeling in which prescribing information is clear and accessible and in complying with the requirements in the final rule on the content and format of labeling for prescription drug and biological products. This guidance is intended to help applicants select information for inclusion in the ``Dosage and Administration'' section of labeling and to help them organize that information.

Intimate insight: MDMA changes how people talk about significant others

PubMed Central

Baggott, Matthew J.; Kirkpatrick, Matthew G.; Bedi, Gillinder; de Wit, Harriet

2015-01-01

Rationale ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions. Method 35 healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a 5-min standardized talking task during which they discussed a close personal relationship (e.g., a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g., words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker’s Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers. Results Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions. Conclusions These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction. PMID:25922420

Intimate insight: MDMA changes how people talk about significant others.

PubMed

Baggott, Matthew J; Kirkpatrick, Matthew G; Bedi, Gillinder; de Wit, Harriet

2015-06-01

±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions. Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker's Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers. Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions. These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction. © The Author(s) 2015.

A Science and Risk-Based Pragmatic Methodology for Blend and Content Uniformity Assessment.

PubMed

Sayeed-Desta, Naheed; Pazhayattil, Ajay Babu; Collins, Jordan; Doshi, Chetan

2018-04-01

This paper describes a pragmatic approach that can be applied in assessing powder blend and unit dosage uniformity of solid dose products at Process Design, Process Performance Qualification, and Continued/Ongoing Process Verification stages of the Process Validation lifecycle. The statistically based sampling, testing, and assessment plan was developed due to the withdrawal of the FDA draft guidance for industry "Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling and Assessment." This paper compares the proposed Grouped Area Variance Estimate (GAVE) method with an alternate approach outlining the practicality and statistical rationalization using traditional sampling and analytical methods. The approach is designed to fit solid dose processes assuring high statistical confidence in both powder blend uniformity and dosage unit uniformity during all three stages of the lifecycle complying with ASTM standards as recommended by the US FDA.

Global approach for the validation of an in-line Raman spectroscopic method to determine the API content in real-time during a hot-melt extrusion process.

PubMed

Netchacovitch, L; Thiry, J; De Bleye, C; Dumont, E; Cailletaud, J; Sacré, P-Y; Evrard, B; Hubert, Ph; Ziemons, E

2017-08-15

Since the Food and Drug Administration (FDA) published a guidance based on the Process Analytical Technology (PAT) approach, real-time analyses during manufacturing processes are in real expansion. In this study, in-line Raman spectroscopic analyses were performed during a Hot-Melt Extrusion (HME) process to determine the Active Pharmaceutical Ingredient (API) content in real-time. The method was validated based on a univariate and a multivariate approach and the analytical performances of the obtained models were compared. Moreover, on one hand, in-line data were correlated with the real API concentration present in the sample quantified by a previously validated off-line confocal Raman microspectroscopic method. On the other hand, in-line data were also treated in function of the concentration based on the weighing of the components in the prepared mixture. The importance of developing quantitative methods based on the use of a reference method was thus highlighted. The method was validated according to the total error approach fixing the acceptance limits at ±15% and the α risk at ±5%. This method reaches the requirements of the European Pharmacopeia norms for the uniformity of content of single-dose preparations. The validation proves that future results will be in the acceptance limits with a previously defined probability. Finally, the in-line validated method was compared with the off-line one to demonstrate its ability to be used in routine analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

Quality evaluation of extemporaneous delayed-release liquid formulations of lansoprazole.

PubMed

Melkoumov, Alexandre; Soukrati, Amina; Elkin, Igor; Forest, Jean-Marc; Hildgen, Patrice; Leclair, Grégoire

2011-11-01

The quality attributes of extemporaneous delayed-release liquid formulations of lansoprazole for oral administration were evaluated. A novel liquid formulation (3 mg/mL) of Prevacid FasTab in an Ora-Blend vehicle was prepared and compared with the Prevacid FasTab 30 mg and Prevacid-sodium bicarbonate 1 M formulation (3 mg/mL). The latter formulation was combined with hydrochloric acid 0.1 N, and the remaining lansoprazole content was assayed by high-performance liquid chromatography (HPLC). A batch of delayed-release liquid formulation was prepared to evaluate content uniformity. For content assay, three samples were prepared for each evaluated condition and each sample was analyzed in triplicate by HPLC. The lansoprazole in the sodium bicarbonate formulation was extensively degraded by quantities of hydrochloric acid 0.1 N in excess of 100 mL. Storage time and temperature had a significant effect on lansoprazole stability in the Ora-Blend formulation. The drug remained stable for seven days when the formulation was stored at 4.5-5.5 °C, but storage at 21-22 °C or the reduction of pH with citric acid accelerated lansoprazole degradation. The amount of lansoprazole released from the Ora-Blend formulation during the buffer stage of the dissolution test decreased with increases in formulation storage time, in formulation storage temperature, and in the amount of lansoprazole released and degraded during the acid stage of the test. An extemporaneous formulation consisting of lansoprazole microgranules in Ora-Blend maintained acceptable quality attributes when stored for three days at 4.5-5.5 °C.

34 CFR 460.3 - What regulations apply to the adult education programs?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Education Programs and Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 460. (c) The...

34 CFR 614.3 - What regulations apply to this program?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (10) 34 CFR part 97 (Protection of Human...

34 CFR 460.3 - What regulations apply to the adult education programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Education Programs and Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 460. (c) The...

34 CFR 460.3 - What regulations apply to the adult education programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Education Programs and Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 460. (c) The...

34 CFR 614.3 - What regulations apply to this program?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (10) 34 CFR part 97 (Protection of Human...

34 CFR 460.3 - What regulations apply to the adult education programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Education Programs and Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 460. (c) The...

34 CFR 614.3 - What regulations apply to this program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Review of Department of Education Programs and Activities). (5) 34 CFR part 80 (Uniform Administrative... (Grants)). (9) 34 CFR part 86 (Drug-Free Schools and Campuses). (10) 34 CFR part 97 (Protection of Human...

34 CFR 460.3 - What regulations apply to the adult education programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Education Programs and Activities). (6) 34 CFR part 80 (Uniform Administrative Requirements for Grants and...) 34 CFR part 86 (Drug-Free Schools and Campuses). (b) The regulations in this part 460. (c) The...

Microfabrication of three-dimensional filters for liposome extrusion

NASA Astrophysics Data System (ADS)

Baldacchini, Tommaso; Nuñez, Vicente; LaFratta, Christopher N.; Grech, Joseph S.; Vullev, Valentine I.; Zadoyan, Ruben

2015-03-01

Liposomes play a relevant role in the biomedical field of drug delivery. The ability of these lipid vesicles to encapsulate and transport a variety of bioactive molecules has fostered their use in several therapeutic applications, from cancer treatments to the administration of drugs with antiviral activities. Size and uniformity are key parameters to take into consideration when preparing liposomes; these factors greatly influence their effectiveness in both in vitro and in vivo experiments. A popular technique employed to achieve the optimal liposome dimension (around 100 nm in diameter) and uniform size distribution is repetitive extrusion through a polycarbonate filter. We investigated two femtosecond laser direct writing techniques for the fabrication of three-dimensional filters within a microfluidics chip for liposomes extrusion. The miniaturization of the extrusion process in a microfluidic system is the first step toward a complete solution for lab-on-a-chip preparation of liposomes from vesicles self-assembly to optical characterization.

States of confusion: Jurisdictional variation in Australian medicines nomenclature.

PubMed

Hope, Denise; King, Michelle

2015-06-01

In December 2000, the Galbally Review recommended Australia achieve national uniformity in drugs and poisons legislation. While the Commonwealth Poisons Standard classifies and schedules medicines and poisons, the Australian States and Territories are responsible for regulating the supply of medicines and poisons through individual medicines legislation. In December 2013, this legislation was examined to identify the nomenclature used to describe medicines. The research found considerable variation across jurisdictions in terms of the nomenclature used, in particular the terms used for Schedules in the State and Territory legislation were often inconsistent with each other and the terms used in the Poisons Standard. Of most concern is that the same term may be used to describe different medicines in different jurisdictions, leading to possible confusion for health practitioners working across jurisdictions as is now possible under national registration. It is therefore imperative that national uniformity of drugs and poisons legislation is achieved to facilitate a common practice reference.

A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

PubMed

Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

2006-01-01

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol-percent DSPE-PEG-maleimide content yielded 1.77+/-0.14 mg/mL liposomal CA4 with 85.70+/-1.71% of this being entrapped in the liposomes. These liposomes, with measured size of 123.84+/-41.23 nm, released no significant amount of the encapsulated drug over 48 h at 37 degrees C.

The development of high-content screening (HCS) technology and its importance to drug discovery.

PubMed

Fraietta, Ivan; Gasparri, Fabio

2016-01-01

High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development. Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology. Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.

Formation of inhalable rifampicin-poly(L-lactide) microparticles by supercritical anti-solvent process.

PubMed

Patomchaiviwat, Vipaluk; Paeratakul, Ornlaksana; Kulvanich, Poj

2008-01-01

Formation of inhalable microparticles containing rifampicin and poly(L-lactide) (L-PLA) by using supercritical anti-solvent process (SAS) was investigated. The solutions of drug and polymer in methylene chloride were sprayed into supercritical carbon dioxide. The effect of polymer content and operating conditions, temperature, pressure, carbon dioxide molar fraction, and concentration of solution, on product characteristics were studied. The prepared microparticles were characterized with respect to their morphology, particle size and size distribution, drug content, drug loading efficiency, and drug release characteristic. Discrete, spherical microparticles were obtained at high polymer:drug ratios of 7:3, 8:2, and 9:1. The shape of L-PLA microparticles became more irregular and agglomerated with decreasing polymer content. Microparticles with polymer content higher than 60% exhibited volumetric mean diameter less than 5 microm, but percent drug loading efficiency was relatively low. Drug-loaded microparticles containing 70% and 80% L-PLA showed a sustainable drug release property without initial burst release. Operating temperature level influenced on mean size and size distribution of microparticles. The operating pressure and carbon dioxide molar fraction in the range investigated were unlikely to have an effect on microparticle formation. An increasing concentration of feed solution provided larger size microparticles. Rifampicin-loaded L-PLA microparticles could be produced by SAS in a size range suitable for dry powder inhaler formulation.

Core Versus Nuclear Gauge Methods of Determining Soil Bulk Density and Moisture Content

Treesearch

Jacqueline G. Steele; Jerry L. Koger; Albert C. Trouse; Donald L. Sirois

1983-01-01

Soil bulk and moisture content measurements were obtained using two nuclear gauge systems and those compared to those obtained from soil cores. The soils, a Hiwassee sandy loam, a Lakeland loamy sand, and a Loyd clay, were free of organic matter and uniform in mechanical composition. The regression equations developed for the nuclear guages for the first phase of the...

21 CFR 516.157 - Publication of the index and content of an index listing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Publication of the index and content of an index listing. 516.157 Section 516.157 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... available through the FDA Web site. A printed copy can be obtained by writing to the FDA Freedom of...

Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique.

PubMed

Rodriguez, Lidia B; Avalos, Abraham; Chiaia, Nicholas; Nadarajah, Arunan

2017-05-01

There are many studies about the synthesis of chitosan microparticles; however, most of them have very low production rate, have wide size distribution, are difficult to reproduce, and use harsh crosslinking agents. Uniform microparticles are necessary to obtain repeatable drug release behavior. The main focus of this investigation was to study the effect of the process and formulation parameters during the preparation of chitosan microparticles in order to produce particles with narrow size distribution. The technique evaluated during this study was emulsion crosslinking technique. Chitosan is a biocompatible and biodegradable material but lacks good mechanical properties; for that reason, chitosan was ionically crosslinked with sodium tripolyphosphate (TPP) at three different ratios (32, 64, and 100%). The model drug used was acetylsalicylic acid (ASA). During the preparation of the microparticles, chitosan was first mixed with ASA and then dispersed in oil containing an emulsifier. The evaporation of the solvents hardened the hydrophilic droplets forming microparticles with spherical shape. The process and formulation parameters were varied, and the microparticles were characterized by their morphology, particle size, drug loading efficiency, and drug release behavior. The higher drug loading efficiency was achieved by using 32% mass ratio of TPP to chitosan. The average microparticle size was 18.7 μm. The optimum formulation conditions to prepare uniform spherical microparticles were determined and represented by a region in a triangular phase diagram. The drug release analyses were evaluated in phosphate buffer solution at pH 7.4 and were mainly completed at 24 h.

Clinical implications of patient-provider agreements in opioid prescribing.

PubMed

Kraus, Carl N; Baldwin, Alan T; Curro, Frederick A; McAllister, R G

2015-01-01

In June, 2012 the United States Food and Drug Administration (FDA) developed a "blueprint" for prescriber education as a means of directing Certified Medical Education (CME) activities that included content which would meet the regulatory requirements of the class-wide, longacting/ extended-release (LA-ER) opioid Risk Evaluation Mitigation Strategies (REMS). Within the blueprint is the suggested adoption of Patient-Provider Agreements (PPAs) to be used in association with opioid prescribing, but, to our knowledge, there have been no reported evaluations of the role played by opioid-agent PPAs in clinical practice, or of the perceptions of this regulatory mandate by clinicians. Therefore, we conducted a survey regarding PPA perceptions by opioid prescribers that was posted for five weeks on a well-trafficked online CME service provider (Medscape). Of the 1,232 respondents (reflecting a 99.5% completion rate), 52.4% treat acute or chronic pain with opioids. The survey identified an improvement of opioid safe-use education (21% of respondents) as the most frequently selected beneficial element of PPAs. Conversely, the challenges to adoption included time constraints (21% of physicians) as well as lack of evidence that PPAs will reduce drug misuse, and the lack of a uniform, patient-friendly PPA. Based on our survey, clinicians consider the PPA of potential value, but data regarding the utility of such an instrument are lacking.

Pharmacokinetics and anti-hypertensive effect of metoprolol tartrate rectal delivery system.

PubMed

Abou el Ela, Amal El Sayeh F; Allam, Ayat A; Ibrahim, Ehsan H

2016-01-01

The main aim of this work was to develop rectal suppositories for better delivery of metoprolol tartrate (MT). The various bases used were fatty, water soluble and emulsion bases. The physical properties of the prepared suppositories were characterized such as weight variation, hardness, disintegration time, melting range and the drug content uniformity. The in vitro release of MT from the prepared suppositories was carried out. The evaluation of the pharmacological effects of MT on the blood pressure and heart rate of the healthy rabbits after the rectal administration compared to the oral tablets was studied. Moreover, the formulation with the highest in vitro release and the highest pharmacological effects would be selected for a further pharmacokinetics study compared to the oral tablets. The results revealed that the emulsion bases gave the highest rate of the drug release than the other bases used. The reduction effect of the emulsion MT suppository base on the blood pressure and heart rate was found to be faster and greater than that administered orally. The selected emulsion suppository base (F11) showed a significant increase in the AUC (1.88-fold) in rabbits as compared to the oral tablets. From the above results we can conclude that rectal route can serve as an efficient alternative route to the oral one for systemic delivery of MT which may be due to the avoidance of first-pass effect in the liver.

Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

PubMed

Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

2018-06-04

Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: Teaching Drug Marketers How to Inform Better or Spin Better? Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Doran, Evan

2016-02-21

Hyosun Kim's report "Trouble Spots in Online Direct to Consumer Prescription Drug Promotion: A content Analysis of FDA Warning Letters" aims to teach marketers how to avoid breaching current Food and Drug Administration (FDA) guidelines in their online drug promotion. While Kim hopes to minimise the potential for online promotion to misinform consumers and the study is carefully conducted, teaching drug marketers how to avoid the common mistakes in online drug promotion is more likely to make marketers more adept at spinning information than appropriately balancing it. © 2016 by Kerman University of Medical Sciences.

Spatially Uniform Tumor Treatment and Drug Penetration by Regulating Ultrasound with Microbubbles.

PubMed

Ho, Yi-Ju; Wang, Tzu-Chia; Fan, Ching-Hsiang; Yeh, Chih-Kuang

2018-05-30

Tumor microenvironment has different morphologies of vessels in the core and rim regions, which influences the efficacy of tumor therapy. Our study proposed to improve the spatial uniformity of the antivascular effect and drug penetration within the tumor core and rim in combination therapies by regulating ultrasound-stimulated microbubble destruction (USMD). Focused ultrasound at 2 MHz and lipid-shell microbubbles (1.12 ± 0.08 μm, mean ± standard deviation) were used to perform USMD. The efficiency of the antivascular effect was evaluated by intravital imaging to determine the optimal USMD parameters. Tumor perfusion and histological alterations in the tumor core and rim were used to analyze the spatial uniformity of the antivascular effect and liposomal-doxorubicin (5 mg/kg) penetration in the combination therapy. Tumor vessels of specific sizes were disrupted by regulating USMD: vessels with sizes of 11 ± 3, 14 ± 5, 19 ± 7, and 23 ± 10 μm were disrupted by stimulation at acoustic pressures of 3, 5, 7, and 9 MPa, respectively (each p < 0.05). The effective treatment time of USMD (at 2 × 10 7 microbubbles/mouse, 7 MPa, and three cycles) was 60-120 min, which resulted in the disruption of 21-44% of vessels smaller than 50 μm. The reductions in perfusion and vascular density after combination therapy did not differ significantly between the tumor core and rim. This study found that regulating USMD can result in homogeneous antivascular effects and drug penetration within tumors and thereby improve the efficacy of combination therapies.

Free nicotine content and strategic marketing of moist snuff tobacco products in the United States: 2000-2006.

PubMed

Alpert, H R; Koh, H; Connolly, G N

2008-10-01

From 2000 to 2006, moist snuff sales have increased and now account for 71% of the smokeless tobacco market. Previous research has shown that major manufacturers of smokeless tobacco products manipulated free nicotine, the form most readily absorbed, to promote tolerance and addiction. This study examines the possibility that company-specific and brand-specific strategies of the major moist snuff manufacturers involve controlling free nicotine content and ease of dosing with products that are designed and targeted to specific groups. This study looks at the current total US moist snuff market with product design data from the Massachusetts Department of Public Health; moist snuff use from the National Survey on Drug Use and Health; market data from ACNielsen; and magazine advertising expenditures from TNS Media Intelligence. (1) The levels of free nicotine of moist snuff products have increased over time for several major manufacturers; (2) the number and variety of sub-brands have increased over time; (3) changes in design, as reflected by variation in free nicotine associated with pH or tobacco leaf, or both, have enhanced the ease and uniformity of dosing; (4) marketing through price and advertising has increased; and (5) youth use has increased. A combination of factors including brand proliferation, control of free nicotine and product design has most likely resulted in the expanded consumption of moist snuff, particularly among young people.

Modeling the motion and orientation of various pharmaceutical tablet shapes in a film coating pan using DEM.

PubMed

Ketterhagen, William R

2011-05-16

Film coating uniformity is an important quality attribute of pharmaceutical tablets. Large variability in coating thickness can limit process efficiency or cause significant variation in the amount or delivery rate of the active pharmaceutical ingredient to the patient. In this work, the discrete element method (DEM) is used to computationally model the motion and orientation of several novel pharmaceutical tablet shapes in a film coating pan in order to predict coating uniformity. The model predictions are first confirmed with experimental data obtained from an equivalent film coating pan using a machine vision system. The model is then applied to predict coating uniformity for various tablet shapes, pan speeds, and pan loadings. The relative effects of these parameters on both inter- and intra-tablet film coating uniformity are assessed. The DEM results show intra-tablet coating uniformity is strongly influenced by tablet shape, and the extent of this can be predicted by a measure of the tablet shape. The tablet shape is shown to have little effect on the mixing of tablets, and thus, the inter-tablet coating uniformity. The pan rotation speed and pan loading are shown to have a small effect on intra-tablet coating uniformity but a more significant impact on inter-tablet uniformity. These results demonstrate the usefulness of modeling in guiding drug product development decisions such as selection of tablet shape and process operating conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

7 CFR 51.891 - Uniform in appearance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... STANDARDS) United States Standards for Grades of Table Grapes (European or Vinifera Type) 1 Definitions § 51... appearance of the contents of the individual container, and that the stems are well developed and strong. [36...

7 CFR 51.891 - Uniform in appearance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS) United States Standards for Grades of Table Grapes (European or Vinifera Type) 1 Definitions § 51... appearance of the contents of the individual container, and that the stems are well developed and strong. [36...

7 CFR 51.891 - Uniform in appearance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... STANDARDS) United States Standards for Grades of Table Grapes (European or Vinifera Type) 1 Definitions § 51... appearance of the contents of the individual container, and that the stems are well developed and strong. [36...

21 CFR 1403.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... Status Report” (or other equivalent report); (2) For construction grants, the SF-271 “Outlay Report and Request for Reimbursement” (or other equivalent report). Federally recognized Indian tribal government...

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

NASA Astrophysics Data System (ADS)

Tang, Yadong; Liu, Li; Li, Junjun; Yu, Leqian; Wang, Li; Shi, Jian; Chen, Yong

2016-07-01

Extensive efforts have been devoted to develop new substrates for culture and differentiation of human induced pluripotent stem cells (hiPSCs) toward cardiac cell-based assays. A more exciting prospect is the construction of cardiac tissue for robust drug screening and cardiac tissue repairing. Here, we developed a patch method by electrospinning and crosslinking of monolayer gelatin nanofibers on a honeycomb frame made of poly(ethylene glycol) diacrylate (PEGDA). The monolayer of the nanofibrous structure can support cells with minimal exogenous contact and a maximal efficiency of cell-medium exchange whereas a single hiPSC colony can be uniformly formed in each of the honeycomb compartments. By modulating the treatment time of the ROCK inhibitor Y-27632, the shape of the hiPSC colony could be controlled from a flat layer to a hemisphere. Afterwards, the induction and differentiation of hiPSCs were achieved on the same patch, leading to a uniform cardiac layer with homogeneous contraction. This cardiac layer could then be used for extracellular recording with a commercial multi-electrode array, showing representative field potential waveforms of matured cardiac tissues with appropriate drug responses.Extensive efforts have been devoted to develop new substrates for culture and differentiation of human induced pluripotent stem cells (hiPSCs) toward cardiac cell-based assays. A more exciting prospect is the construction of cardiac tissue for robust drug screening and cardiac tissue repairing. Here, we developed a patch method by electrospinning and crosslinking of monolayer gelatin nanofibers on a honeycomb frame made of poly(ethylene glycol) diacrylate (PEGDA). The monolayer of the nanofibrous structure can support cells with minimal exogenous contact and a maximal efficiency of cell-medium exchange whereas a single hiPSC colony can be uniformly formed in each of the honeycomb compartments. By modulating the treatment time of the ROCK inhibitor Y-27632, the shape of the hiPSC colony could be controlled from a flat layer to a hemisphere. Afterwards, the induction and differentiation of hiPSCs were achieved on the same patch, leading to a uniform cardiac layer with homogeneous contraction. This cardiac layer could then be used for extracellular recording with a commercial multi-electrode array, showing representative field potential waveforms of matured cardiac tissues with appropriate drug responses. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr04545f

Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Jin, Erlei

2011-12-01

Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

Marketing pharmaceutical drugs to women in magazines: a content analysis.

PubMed

Sokol, Jennifer; Wackowski, Olivia; Lewis, M J

2010-01-01

To examine the prevalence and content of pharmaceutical ads in demographically different women's magazines. A content analysis was conducted using one year's worth of 5 different women's magazines of varying age demographics. Magazines differed in the proportion of drug ads for different health conditions (eg, cardiovascular) and target audience by age demographic. Use of persuasive elements (types of appeals, evidence) varied by condition promoted (eg, mental-health drug ads more frequently used emotional appeals). Ads placed greater emphasis on direction to industry information resources than on physician discussions. Prevalence of pharmaceutical advertising in women's magazines is high; continued surveillance is recommended.

21 CFR 130.10 - Requirements for foods named by use of a nutrient content claim and a standardized term.

Code of Federal Regulations, 2010 CFR

2010-04-01

... properties, flavor characteristics, functional properties, shelf life) of the food shall be similar to those... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Requirements for foods named by use of a nutrient content claim and a standardized term. 130.10 Section 130.10 Food and Drugs FOOD AND DRUG ADMINISTRATION...

21 CFR 130.10 - Requirements for foods named by use of a nutrient content claim and a standardized term.

Code of Federal Regulations, 2011 CFR

2011-04-01

... properties, flavor characteristics, functional properties, shelf life) of the food shall be similar to those... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Requirements for foods named by use of a nutrient content claim and a standardized term. 130.10 Section 130.10 Food and Drugs FOOD AND DRUG ADMINISTRATION...

21 CFR 516.145 - Content and format of a request for addition to the index.

Code of Federal Regulations, 2010 CFR

2010-04-01

... qualified expert panel meets the selection criteria provided for in § 516.141(b); (3) A written report that... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Content and format of a request for addition to the index. 516.145 Section 516.145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH...

Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis.

PubMed

Sharma, Rahul; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2016-01-01

The present study is designed to explore the localized delivery of fluconazole using mucoadhesive polymeric nanofibers. Drug-loaded polymeric nanofibers were fabricated by the electrospinning method using polyvinyl alcohol (PVA) as the polymeric constituent. The prepared nanofibers were found to be uniform, non-beaded and non-woven, with the diameter of the fibers ranging from 150 to 180 nm. Further drug release studies indicate a sustained release of fluconazole over a period of 6 h. The results of studies on anti-microbial activity indicated that drug-loaded polymeric nanofibers exhibit superior anti-microbial activity against Candida albicans, when compared to the plain drug.

[Changes in emotional response to visual stimuli with sexual content in drug abusers].

PubMed

Aguilar de Arcos, Francisco; Verdejo Garcia, Antonio; Lopez Jimenez, Angeles; Montañez Pareja, Matilde; Gomez Juarez, Encarnacion; Arraez Sanchez, Francisco; Perez Garcia, Miguel

2008-01-01

In a phenomenon as complex as drug dependence there is no doubt that affective and emotional aspects are involved. However, there has been little research to date on these emotional aspects, especially in specific relation to everyday affective stimuli, unrelated to drug use. In this work we investigate whether the consumption of narcotic substances causes changes in the emotional response to powerful unconditional natural stimuli, such as those of a sexual nature. To this end, I.A.P.S. images with explicit erotic content were shown to 84 drug-dependent males, in separate groups according to preferred substance. These groups' results were compared with each other and with the values obtained by non-consumers. The results indicate that drug abusers respond differently to visual stimuli with erotic content compared to non-consumers, and that there are also differences in response among consumers according to preferred substance.

Knowledge engineering for adverse drug event prevention: on the design and development of a uniform, contextualized and sustainable knowledge-based framework.

PubMed

Koutkias, Vassilis; Kilintzis, Vassilis; Stalidis, George; Lazou, Katerina; Niès, Julie; Durand-Texte, Ludovic; McNair, Peter; Beuscart, Régis; Maglaveras, Nicos

2012-06-01

The primary aim of this work was the development of a uniform, contextualized and sustainable knowledge-based framework to support adverse drug event (ADE) prevention via Clinical Decision Support Systems (CDSSs). In this regard, the employed methodology involved first the systematic analysis and formalization of the knowledge sources elaborated in the scope of this work, through which an application-specific knowledge model has been defined. The entire framework architecture has been then specified and implemented by adopting Computer Interpretable Guidelines (CIGs) as the knowledge engineering formalism for its construction. The framework integrates diverse and dynamic knowledge sources in the form of rule-based ADE signals, all under a uniform Knowledge Base (KB) structure, according to the defined knowledge model. Equally important, it employs the means to contextualize the encapsulated knowledge, in order to provide appropriate support considering the specific local environment (hospital, medical department, language, etc.), as well as the mechanisms for knowledge querying, inference, sharing, and management. In this paper, we present thoroughly the establishment of the proposed knowledge framework by presenting the employed methodology and the results obtained as regards implementation, performance and validation aspects that highlight its applicability and virtue in medication safety. Copyright © 2012 Elsevier Inc. All rights reserved.

Food labeling: nutrient content claims, expansion of the nutrient content claim "lean". Final rule.

PubMed

2007-01-12

The Food and Drug Administration (FDA) is amending its food labeling regulations for the expanded use of the nutrient content claim "lean" on the labels of foods categorized as "mixed dishes not measurable with a cup" that meet certain criteria for total fat, saturated fat, and cholesterol content. This final rule responds to a nutrient content claim petition submitted by Nestlé Prepared Foods Co. (Nestlé) under the Federal Food, Drug, and Cosmetic Act (the act). This action is also being taken to provide reliable information that would assist consumers in maintaining healthy dietary practices.

Doped zinc oxide microspheres

DOEpatents

Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

1993-01-01

A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

Highly uniform and stable cerasomal microcapsule with good biocompatibility for drug delivery.

PubMed

Zhang, Chun-Yang; Cao, Zhong; Zhu, Wen-Jian; Liu, Jie; Jiang, Qing; Shuai, Xin-Tao

2014-04-01

Efforts to improve the stability of liposomes have recently led to the development of organic-inorganic liposomal cerasomes. However, the uncontrollable size of cerasomes has greatly limited their biomedical applications. In this study, a novel strategy was introduced to fabricate hybrid liposomal cerasomes with high stability and uniform size. The hybrid lipids were first deposited onto CaCO3 microspheres through electrostatic interactions and self-assembly, and then the CaCO3 core was removed to obtain hollow microcapsules, i.e. the cerasomes. The species of the lipid oligomers was detected by MALDI-TOF-MS, which demonstrates the existence of siloxane network on microcapsules' surface. Anticancer drug doxorubicin hydrochloride (DOX) loaded cerasomal microcapsule (DLCM) exhibited an initial burst release behavior followed by the sustained release and remarkably high stability towards surfactant solubilization and long term storage. The DLCM displayed a pH-dependent and sustained DOX release profile in vitro, which can be well explained using a well established mathematical model. Our results indicate that these novel cerasomal microcapsules have great potential to be applied as drug delivery system in cancer therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Terahertz pulsed imaging as an advanced characterisation tool for film coatings--a review.

PubMed

Haaser, Miriam; Gordon, Keith C; Strachan, Clare J; Rades, Thomas

2013-12-05

Solid dosage forms are the pharmaceutical drug delivery systems of choice for oral drug delivery. These solid dosage forms are often coated to modify the physico-chemical properties of the active pharmaceutical ingredients (APIs), in particular to alter release kinetics. Since the product performance of coated dosage forms is a function of their critical coating attributes, including coating thickness, uniformity, and density, more advanced quality control techniques than weight gain are required. A recently introduced non-destructive method to quantitatively characterise coating quality is terahertz pulsed imaging (TPI). The ability of terahertz radiation to penetrate many pharmaceutical materials enables structural features of coated solid dosage forms to be probed at depth, which is not readily achievable with other established imaging techniques, e.g. near-infrared (NIR) and Raman spectroscopy. In this review TPI is introduced and various applications of the technique in pharmaceutical coating analysis are discussed. These include evaluation of coating thickness, uniformity, surface morphology, density, defects and buried structures as well as correlation between TPI measurements and drug release performance, coating process monitoring and scale up. Furthermore, challenges and limitations of the technique are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Stakeholder Perceptions of Cyberbullying Cases: Application of the Uniform Definition of Bullying.

PubMed

Moreno, Megan A; Suthamjariya, Nina; Selkie, Ellen

2018-04-01

The Uniform Definition of Bullying was developed to address bullying and cyberbullying, and to promote consistency in measurement and policy. The purpose of this study was to understand community stakeholder perceptions of typical cyberbullying cases, and to evaluate how these case descriptions align with the Uniform Definition. In this qualitative case analysis we recruited stakeholders commonly involved in cyberbullying. We used purposeful sampling to identify and recruit adolescents and young adults, parents, and professionals representing education and health care. Participants were asked to write a typical case of cyberbullying and descriptors in the context of a group discussion. We applied content analysis to case excerpts using inductive and deductive approaches, and chi-squared tests for mixed methods analyses. A total of 68 participants contributed; participants included 73% adults and 27% adolescents and young adults. A total of 650 excerpts were coded from participants' example cases and 362 (55.6%) were consistent with components of the Uniform Definition. The most frequently mentioned component of the Uniform Definition was Aggressive Behavior (n = 218 excerpts), whereas Repeated was mentioned infrequently (n = 19). Most participants included two to three components of the Uniform Definition within an example case; none of the example cases included all components of the Uniform Definition. We found that most participants described cyberbullying cases using few components of the Uniform Definition. Findings can be applied toward considering refinement of the Uniform Definition to ensure stakeholders find it applicable to cyberbullying. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Single and Dual Drug Release Patterns from Shellac Wax-Lutrol Matrix Tablets Fabricated with Fusion and Molding Techniques

PubMed Central

Phaechamud, T.; Choncheewa, C.

2015-01-01

The objective of this investigation was to prepare the shellac wax matrix tablets by fusion and molding technique incorporated with Lutrol in different ratios to modify the hydrophobicity of matrix tablet. The matrix tablets with single drug were loaded either with propranolol hydrochloride or hydrochlorothiazide as hydrophilic and hydrophobic model drugs, and a dual drug formula was also prepared. The single and dual drug release patterns were studied in a dissolution apparatus using distilled water as medium. Propranolol hydrochloride released from matrix was easier than hydrochlorothiazide. Drug release from shellac wax matrix could be enhanced by incorporation of Lutrol. However retardation of drug release from some matrix tablets was evident for the systems that could form dispersion in the dissolution medium. The gel network from high content of Lutrol was hexagonal which was a dense and more compact structure than the other structures found when low amounts of Lutrol were present in the formula. Therefore, the formulae with high content of Lutrol could prolong drug release more efficiently than those containing low content of Lutrol. Hence shellac wax matrix could modulate the drug release with the addition of Lutrol. Sustainable dual drug release was also obtained from these developed matrix tablets. Thus shellac wax-Lutrol component could be used as a potential matrix tablet prepared with fusion and molding technique with excellent controlled drug release. PMID:25767320

Nanomedicine in pulmonary delivery

PubMed Central

Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

2009-01-01

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

Uniform nanoparticles by flame-assisted spray pyrolysis (FASP) of low cost precursors

PubMed Central

Rudin, Thomas; Wegner, Karsten

2013-01-01

A new flame-assisted spray pyrolysis (FASP) reactor design is presented, which allows the use of inexpensive precursors and solvents (e.g., ethanol) for synthesis of nanoparticles (10–20 nm) with uniform characteristics. In this reactor design, a gas-assisted atomizer generates the precursor solution spray that is mixed and combusted with externally fed inexpensive fuel gases (acetylene or methane) at a defined height above the atomizing nozzle. The gaseous fuel feed can be varied to control the combustion enthalpy content of the flame and onset of particle formation. This way, the enthalpy density of the flame is decoupled from the precursor solution composition. Low enthalpy content precursor solutions are prone to synthesis of non-uniform particles (e.g., bimodal particle size distribution) by standard flame spray pyrolysis (FSP) processes. For example, metal nitrates in ethanol typically produce nanosized particles by gas-to-particle conversion along with larger particles by droplet-to-particle conversion. The present FASP design facilitates the use of such low enthalpy precursor solutions for synthesis of homogeneous nanopowders by increasing the combustion enthalpy density of the flame with low-cost, gaseous fuels. The effect of flame enthalpy density on product properties in the FASP configuration is explored by the example of Bi2O3 nanoparticles produced from bismuth nitrate in ethanol. Product powders were characterized by nitrogen adsorption, X-ray diffraction, X-ray disk centrifuge, and transmission electron microscopy. Homogeneous Bi2O3 nanopowders were produced both by increasing the gaseous fuel content and, most notably, by cutting the air entrainment prior to ignition of the spray. PMID:23408113

Nondestructive hydrogen analysis of steam-oxidized Zircaloy-4 by wide-angle neutron scattering

NASA Astrophysics Data System (ADS)

Yan, Yong; Qian, Shuo; Garrison, Ben; Smith, Tyler; Kim, Peter

2018-04-01

A nondestructive neutron scattering method to precisely measure the hydrogen content in high-temperature steam-oxidized Zircaloy-4 cladding was developed. Zircaloy-4 cladding was used to produce hydrided specimens with hydrogen content up to ≈500 wppm. Following hydrogen charging, the hydrogen content of the hydrided specimens was measured using the vacuum hot extraction method, by which the samples with desired hydrogen concentrations were selected for the neutron study. The hydrided samples were then oxidized in steam up to ≈6.0 wt. % at 1100 °C. Optical microscopy shows that our hydriding procedure results in uniform distribution of circumferential hydrides across the wall thickness, and uniform oxide layers were formed on the sample surfaces by the steam oxidation. Small- and wide-angle neutron scattering were simultaneously performed to provide a quick (less than an hour per sample) measurement of the hydrogen content in various types of hydrided and oxidized Zircaloy-4. Our study demonstrates that the hydrogen in pre-oxidized Zircaloy-4 cladding can be measured very accurately by both small- and wide-angle neutron scattering. For steam-oxidized samples, the small-angle neutron scattering is contaminated with coherent scattering from additional structural features induced by the steam oxidation. However, the scattering intensity of the wide-angle neutron scattering increases proportionally with the hydrogen charged in the samples. The hydrogen content and wide-angle neutron scattering intensity are highly linearly correlated for the oxidized cladding samples examined in this work, and can be used to precisely determine the hydrogen content in steam-oxidized Zircaloy-4 samples. Hydrogen contents determined by neutron scattering of oxidation samples were also found to be consistent with the results of chemical analysis within acceptable margins for error.

Nondestructive hydrogen analysis of steam-oxidized Zircaloy-4 by wide-angle neutron scattering

DOE PAGES

Yan, Yong; Qian, Shuo; Garrison, Ben; ...

2018-04-15

In this study, a nondestructive neutron scattering method to precisely measure the hydrogen content in high-temperature steam-oxidized Zircaloy-4 cladding was developed. Zircaloy-4 cladding was used to produce hydrided specimens with hydrogen content up to ≈500 wppm. Following hydrogen charging, the hydrogen content of the hydrided specimens was measured using the vacuum hot extraction method, by which the samples with desired hydrogen concentrations were selected for the neutron study. The hydrided samples were then oxidized in steam up to ≈6.0wt. % at 1100°C. Optical microscopy shows that our hydriding procedure results in uniform distribution of circumferential hydrides across the wall thickness,more » and uniform oxide layers were formed on the sample surfaces by the steam oxidation. Small- and wide-angle neutron scattering were simultaneously performed to provide a quick (less than an hour per sample) measurement of the hydrogen content in various types of hydrided and oxidized Zircaloy-4. Our study demonstrates that the hydrogen in pre-oxidized Zircaloy-4 cladding can be measured very accurately by both small- and wide-angle neutron scattering. For steam-oxidized samples, the small-angle neutron scattering is contaminated with coherent scattering from additional structural features induced by the steam oxidation. However, the scattering intensity of the wide-angle neutron scattering increases proportionally with the hydrogen charged in the samples. The hydrogen content and wide-angle neutron scattering intensity are highly linearly correlated for the oxidized cladding samples examined in this work, and can be used to precisely determine the hydrogen content in steam-oxidized Zircaloy-4 samples. Hydrogen contents determined by neutron scattering of oxidation samples were also found to be consistent with the results of chemical analysis within acceptable margins for error.« less

Nondestructive hydrogen analysis of steam-oxidized Zircaloy-4 by wide-angle neutron scattering

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

Yan, Yong; Qian, Shuo; Garrison, Ben

In this study, a nondestructive neutron scattering method to precisely measure the hydrogen content in high-temperature steam-oxidized Zircaloy-4 cladding was developed. Zircaloy-4 cladding was used to produce hydrided specimens with hydrogen content up to ≈500 wppm. Following hydrogen charging, the hydrogen content of the hydrided specimens was measured using the vacuum hot extraction method, by which the samples with desired hydrogen concentrations were selected for the neutron study. The hydrided samples were then oxidized in steam up to ≈6.0wt. % at 1100°C. Optical microscopy shows that our hydriding procedure results in uniform distribution of circumferential hydrides across the wall thickness,more » and uniform oxide layers were formed on the sample surfaces by the steam oxidation. Small- and wide-angle neutron scattering were simultaneously performed to provide a quick (less than an hour per sample) measurement of the hydrogen content in various types of hydrided and oxidized Zircaloy-4. Our study demonstrates that the hydrogen in pre-oxidized Zircaloy-4 cladding can be measured very accurately by both small- and wide-angle neutron scattering. For steam-oxidized samples, the small-angle neutron scattering is contaminated with coherent scattering from additional structural features induced by the steam oxidation. However, the scattering intensity of the wide-angle neutron scattering increases proportionally with the hydrogen charged in the samples. The hydrogen content and wide-angle neutron scattering intensity are highly linearly correlated for the oxidized cladding samples examined in this work, and can be used to precisely determine the hydrogen content in steam-oxidized Zircaloy-4 samples. Hydrogen contents determined by neutron scattering of oxidation samples were also found to be consistent with the results of chemical analysis within acceptable margins for error.« less

[Affect regularity of medicinal species and heating time on flavonoids contents in Epimedium cut crude drug].

PubMed

Sun, E; Chen, Ling-ling; Jia, Xiao-bin; Qian, Qian; Cui, Li

2012-09-01

To study the affect regularity of medicinal species and heating time on flavonoids contents in Epimedium cut crude drug. Setting processing temperature at 170 degrees C, 39 batches Epimedium cut crude drug of different species were heated for 0, 5, 10 minutes. The contents of epimedin A, B, C, icariin, Baohuoside I in different species of Epimedium were determined by HPLC. The variance analysis was used to study the effect of medicinal species and heating time on the contents change of five major flavonoids. The contents of Epimedin A, B, C were significantly impacted by medicinal species (P < 0.01), and Baohuoside I was also impacted (P < 0. 05). The contents of Epimedin A, B, icariin and Baohuoside I were significantly impacted by heating time (P < 0.01). But the flavonoids contents in Epimedium were not impacted by the interaction effect of heating time and species (P > 0.05). The medicinal species and heat processed time are two important influence factors on the flavonoids contents in Epimedium. The contents of Epimedin A, C are abundant in Epimedium pubescens, and the contents of Epimedin B, Baohuoside I are higher in Epimedium brevicornu. After heating, the contents of Epimedin A, B, C are decreased, and icariin, Baohuoside I are increased. This study provides scientific evidences for variety certification, optimizing processing technology, exploring processing mechanism and clinical rational administration.

Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic β-cell line.

PubMed

Mooranian, Armin; Negrulj, Rebecca; Arfuso, Frank; Al-Salami, Hani

2016-11-01

We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic β-cells. Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-α concentrations. CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels. The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment.

Development of Uniform Protocol for Alopecia Areata Clinical Trials.

PubMed

Solomon, James A

2015-11-01

Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies.

Bainitic stabilization of austenite in low alloy sheet steels

NASA Astrophysics Data System (ADS)

Brandt, Mitchell L.

The stabilization of retained austenite in 'triple phase' ferrite/bainite/austenite sheet steels by isothermal bainite transformation after intercritical annealing has been studied in 0.27C-1.5Si steels with 0.8 to 2.4Mn. Dilatometric studies show that cooling rates comparable to CAPL processing result in approximately 30% conversion of austenite to epitaxial ferrite, but the reaction can be suppressed by the faster cooling rate of salt bath quenching. Measured isothermal transformation kinetics at 350 to 450sp°C shows a maximum overall rate near 400sp°C. X-ray diffraction shows that the amount of austenite retained from 400sp°C treatment peaks at 3 minutes but the carbon content increases monotonically to a saturation level. The stability of austenite in this type of steel has been quantified for the first time by direct measurement of the characteristic Msbsps{sigma} temperature. With variations in processing conditions and test temperatures, the tensile uniform ductility has been correlated with the amount and stability of retained austenite, while maintaining a constant 3% flow of 83 ksi. Consistent with previous transformations plasticity studies an optimal austenite stability is found at approximately 10 K above the Msbsps{sigma} temperature, demonstrating a maximum uniform ductility of 44% for an austenite content of 16%. Correlations indicate that desired uniform ductility levels of 20 to 25% could be achieved with only approximately 5% austenite if stability is optimized by placing Msbsps{sigma} 10 K below ambient temperature. Measured uniform ductility in plane strain tension shows similar trends with processing conditions, but models predict that stress state effects will shift the Msbsps{sigma} temperature approximately 5 K higher than that for uniaxial tension. The measured dependence of Msbsps{sigma} on austenite composition and particle size has been modeled via heterogeneous nucleation theory. The composition dependence is consistent with contributions from the transformation chemical driving force and the interfacial frictional work from solution hardening. An inverse dependence on the log of the particle volume is consistent with statistics of heterogeneous nucleation. The observed austenite carbon content at the end of bainitic transformation is consistent with paraequilibrium calculations adding a stored energy term to the bainitic ferrite. The model predicts that optimal austenite stability for maximum uniform ductility can be achieved at fixed particle size by lowering Mn and/or reducing the isothermal bainite transformation temperature.

45 CFR 92.4 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (Community Services; Preventive Health and Health Services; Alcohol, Drug Abuse, and Mental Health Services... Block Grant and Part C of Title V, Mental Health Service for the Homeless Block Grant). (3) Grants to... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS...

45 CFR 92.4 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... (Community Services; Preventive Health and Health Services; Alcohol, Drug Abuse, and Mental Health Services... Block Grant and Part C of Title V, Mental Health Service for the Homeless Block Grant). (3) Grants to... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS...

45 CFR 92.4 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (Community Services; Preventive Health and Health Services; Alcohol, Drug Abuse, and Mental Health Services... Block Grant and Part C of Title V, Mental Health Service for the Homeless Block Grant). (3) Grants to... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS...

Doped zinc oxide microspheres

DOEpatents

Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

1993-12-14

A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

Errors in reporting on dissolution research: methodological and statistical implications.

PubMed

Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

2017-02-01

In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. A clearer description of the procedures would undoubtedly increase the quality of papers in this area.

Exploration of ethyl anthranilate-loaded monolithic matrix-type prophylactic polymeric patch.

PubMed

Islam, Johirul; Zaman, Kamaruz; Chakrabarti, Srijita; Bora, Nilutpal Sharma; Pathak, Manash Pratim; Mandal, Santa; Junejo, Julfikar Ali; Chattopadhyay, Pronobesh

2017-10-01

Compromised stability of pharmaceutical formulations loaded with volatiles is a serious problem associated with devices designed to deliver volatile compounds. The present study has been focused to evaluate the stability potential of matrix-type polymeric patches composed of volatile ethyl anthranilate for prophylaxis against vector-borne diseases. Ethyl anthranilate-loaded matrix-type polymeric patches were fabricated by solvent evaporation method on an impermeable backing membrane and attached to temporary release liners. Stability testing of the polymeric patches was performed as per the International Conference on Harmonization (ICH) guidelines for 6 months under accelerated conditions. In addition, the quantification of residual solvents was also performed as per the ICH guidelines. After conducting the stability studies for 6 months, the optimized patches showed the best possible results with respect to uniformity of drug content, physical appearance, and other analytical parameters. Furthermore, the amount of residual solvent was found well below the accepted limit. Thus, the present report outlined the analytical parameters to be evaluated to ensure the stability of a certain devices consisting of volatile compounds. Copyright © 2016. Published by Elsevier B.V.

Functionalised particles using dry powder coating in pharmaceutical drug delivery: promises and challenges.

PubMed

Dahmash, Eman Z; Mohammed, Afzal R

2015-01-01

Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Pharmaceutical drugs chatter on Online Social Networks.

PubMed

Wiley, Matthew T; Jin, Canghong; Hristidis, Vagelis; Esterling, Kevin M

2014-06-01

The ubiquity of Online Social Networks (OSNs) is creating new sources for healthcare information, particularly in the context of pharmaceutical drugs. We aimed to examine the impact of a given OSN's characteristics on the content of pharmaceutical drug discussions from that OSN. We compared the effect of four distinguishing characteristics from ten different OSNs on the content of their pharmaceutical drug discussions: (1) General versus Health OSN; (2) OSN moderation; (3) OSN registration requirements; and (4) OSNs with a question and answer format. The effects of these characteristics were measured both quantitatively and qualitatively. Our results show that an OSN's characteristics indeed affect the content of its discussions. Based on their information needs, healthcare providers may use our findings to pick the right OSNs or to advise patients regarding their needs. Our results may also guide the creation of new and more effective domain-specific health OSNs. Further, future researchers of online healthcare content in OSNs may find our results informative while choosing OSNs as data sources. We reported several findings about the impact of OSN characteristics on the content of pharmaceutical drug discussion, and synthesized these findings into actionable items for both healthcare providers and future researchers of healthcare discussions on OSNs. Future research on the impact of OSN characteristics could include user demographics, quality and safety of information, and efficacy of OSN usage. Copyright © 2014 Elsevier Inc. All rights reserved.

Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP.

PubMed

Al-Zoubi, Nizar; Al-Obaidi, Ghada; Tashtoush, Bassam; Malamataris, Stavros

2016-01-01

In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R(2) > 0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f2 > 50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.

Formation of Uniform Hollow Silica microcapsules

NASA Astrophysics Data System (ADS)

Yan, Huan; Kim, Chanjoong

2012-02-01

Microcapsules are small containers with diameters in the range of 0.1 -- 100 μm. Mesoporous microcapsules with hollow morphologies possess unique properties such as low-density and high encapsulation capacity, while allowing controlled release by permeating substances with a specific size and chemistry. Our process is a one-step fabrication of monodisperse hollow silica capsules with a hierarchical pore structure and high size uniformity using double emulsion templates obtained by the glass-capillary microfluidic technique to encapsulate various active ingredients. These hollow silica microcapsules can be used as biomedical applications such as drug delivery and controlled release.

Formation of Uniform Hollow Silica microcapsules

NASA Astrophysics Data System (ADS)

Yan, Huan; Kim, Chanjoong

2013-03-01

Microcapsules are small containers with diameters in the range of 0.1 - 100 μm. Mesoporous microcapsules with hollow morphologies possess unique properties such as low-density and high encapsulation capacity, while allowing controlled release by permeating substances with a specific size and chemistry. Our process is a one-step fabrication of monodisperse hollow silica capsules with a hierarchical pore structure and high size uniformity using double emulsion templates obtained by the glass-capillary microfluidic technique to encapsulate various active ingredients. These hollow silica microcapsules can be used as biomedical applications such as drug delivery and controlled release.

The content of Psilocybin in Norwegian Psilocybe semilanceata.

PubMed

Christiansen, A L; Rasmussen, K E; Høiland, K

1981-07-01

Psilocybe semilanceata contains hallucinogenic indole alkaloids and has been used as a narcotic drug in Norway. The content of psilocybin, the major constituent in Norwegian P. semilanceata, has been investigated as well as its habitats and its distribution throughout the country. The mushroom is growing on grassy sites in most parts of Norway from the middle of August to the middle of October. The psilocybin content in dried mushrooms varied considerably, from 0.17 to 1.96%. The highest concentrations in percent was found among the smaller mushrooms whereas the content in mg was highest in larger mushrooms. The content of psilocybin makes P. semilanceata to a potent hallucinogenic drug.

Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation

PubMed Central

Schneider, Craig S.; Xu, Qingguo; Boylan, Nicholas J.; Chisholm, Jane; Tang, Benjamin C.; Schuster, Benjamin S.; Henning, Andreas; Ensign, Laura M.; Lee, Ethan; Adstamongkonkul, Pichet; Simons, Brian W.; Wang, Sho-Yu S.; Gong, Xiaoqun; Yu, Tao; Boyle, Michael P.; Suk, Jung Soo; Hanes, Justin

2017-01-01

Mucoadhesive particles (MAP) have been widely explored for pulmonary drug delivery because of their perceived benefits in improving particle residence in the lungs. However, retention of particles adhesively trapped in airway mucus may be limited by physiologic mucus clearance mechanisms. In contrast, particles that avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized would provide prolonged lung retention compared to MAP. We compared in vivo behaviors of variously sized, polystyrene-based MAP and MPP in the lungs following inhalation. MAP, regardless of particle size, were aggregated and poorly distributed throughout the airways, leading to rapid clearance from the lungs. Conversely, MPP as large as 300 nm exhibited uniform distribution and markedly enhanced retention compared to size-matched MAP. On the basis of these findings, we formulated biodegradable MPP (b-MPP) with an average diameter of <300 nm and examined their behavior following inhalation relative to similarly sized biodegradable MAP (b-MAP). Although b-MPP diffused rapidly through human airway mucus ex vivo, b-MAP did not. Rapid b-MPP movements in mucus ex vivo correlated to a more uniform distribution within the airways and enhanced lung retention time as compared to b-MAP. Furthermore, inhalation of b-MPP loaded with dexamethasone sodium phosphate (DP) significantly reduced inflammation in a mouse model of acute lung inflammation compared to both carrier-free DP and DP-loaded MAP. These studies provide a careful head-to-head comparison of MAP versus MPP following inhalation and challenge a long-standing dogma that favored the use of MAP for pulmonary drug delivery. PMID:28435870

Synthesis of silica nanoparticles for encapsulation of oncology drugs with low water solubility: effect of processing parameters on structural evolution

NASA Astrophysics Data System (ADS)

Bürglová, Kristýna; Hlaváč, Jan; Bartlett, John R.

2015-12-01

Silica nanoparticles with tailored properties have been developed for a variety of biomedical applications, with particular emphasis on their use as carriers for the encapsulation and controlled release of bioactive species. Among the various strategies described, silica nanoparticles with uniform mesoporosity (MSN) prepared in aqueous solution at elevated temperatures using cetyltrimethylammonium bromide as a template have a range of desirable properties. However, the processing windows available to control the dimensions and other key properties of such nanoparticles prepared using fluoride salts as catalysts have not been elucidated, with mixed products containing gel fragments and non-uniform products obtained under many conditions. Here, we present a parametric study of the synthesis of MSN under fluoride-catalysed conditions using tetraethylorthosilicate as silica precursor. The processing conditions required to produce uniform nanoparticles with controlled dimensions are elucidated, together with the conditions under which dried powders can be re-dispersed in aqueous solution after long-term storage to regenerate unaggregated nanospheres with dimensions (as measured by dynamic light scattering) comparable to those measured via scanning electron microscopy analysis of the dried material. The ability to dry and store such powders for extended periods of time is an important requirement for the use of such materials in drug delivery applications. Preliminary results demonstrating the use of such MSNs as hosts for oncology drugs [substituted 3-hydroxyquinolinones ( 3-HQ)] with low water solubility (≪1 µg/g H2O) are presented, with loadings of several wt% demonstrated. The ability of the silica host to protect the 3-HQ from oxidative degradation during impregnation and release is discussed.

Acoustically enhanced microfluidic mixer to synthesize highly uniform nanodrugs without the addition of stabilizers.

PubMed

Le, Nguyen Hoai An; Van Phan, Hoang; Yu, Jiaqi; Chan, Hak-Kim; Neild, Adrian; Alan, Tuncay

2018-01-01

This article presents an acoustically enhanced microfluidic mixer to generate highly uniform and ultra-fine nanoparticles, offering significant advantages over conventional liquid antisolvent techniques. The method employed a 3D microfluidic geometry whereby two different phases - solvent and antisolvent - were introduced at either side of a 1 μm thick resonating membrane, which contained a through-hole. The vibration of the membrane rapidly and efficiently mixed the two phases, at the location of the hole, leading to the formation of nanoparticles. The versatility of the device was demonstrated by synthesizing budesonide (a common asthma drug) with a mean diameter of 135.7 nm and a polydispersity index of 0.044. The method offers a 40-fold reduction in the size of synthesized particles combined with a substantial improvement in uniformity, achieved without the need of stabilizers.

Spherical Macroporous Carbon Nanotube Particles with Ultrahigh Sulfur Loading for Lithium-Sulfur Battery Cathodes.

PubMed

Gueon, Donghee; Hwang, Jeong Tae; Yang, Seung Bo; Cho, Eunkyung; Sohn, Kwonnam; Yang, Doo-Kyung; Moon, Jun Hyuk

2018-01-23

A carbon host capable of effective and uniform sulfur loading is the key for lithium-sulfur batteries (LSBs). Despite the application of porous carbon materials of various morphologies, the carbon hosts capable of uniformly impregnating highly active sulfur is still challenging. To address this issue, we demonstrate a hierarchical pore-structured CNT particle host containing spherical macropores of several hundred nanometers. The macropore CNT particles (M-CNTPs) are prepared by drying the aerosol droplets in which CNTs and polymer particles are dispersed. The spherical macropore greatly improves the penetration of sulfur into the carbon host in the melt diffusion of sulfur. In addition, the formation of macropores greatly develops the volume of the micropore between CNT strands. As a result, we uniformly impregnate 70 wt % sulfur without sulfur residue. The S-M-CNTP cathode shows a highly reversible capacity of 1343 mA h g -1 at a current density of 0.2 C even at a high sulfur content of 70 wt %. Upon a 10-fold current density increase, a high capacity retention of 74% is observed. These cathodes have a higher sulfur content than those of conventional CNT hosts but nevertheless exhibit excellent performance. Our CNTPs and pore control technology will advance the commercialization of CNT hosts for LSBs.

[Uniform analyzes of drugs in urine needed for rule of law].

PubMed

Hansson, Therese; Helander, Anders; Beck, Olof; Elmgren, Anders; Kugelberg, Fredrik; Kronstrand, Robert

2015-09-22

Drugs of abuse testing is used in various areas of society for detection and follow-up of drug use. In routine laboratory drug testing, immunoassays are employed for initial screening of specimens to indicate the presence of drugs. To confirm a positive screening test, a secondary analysis by mass spectrometry is performed. The "cut-off" is the pre-defined concentration threshold of a drug or drug metabolite above which the sample is considered positive. A reading below this level implies a negative test result. Swedish drug testing laboratories currently employ varying cut-offs to distinguish between a positive and a negative test result. Because a positive drug test may have serious legal consequences to the individual, it is of importance that testing is performed and judged equally, regardless of where it is performed. A national harmonization of cut-offs is therefore warranted. Based on data from four major Swedish drug testing laboratories, and considering the recommendations in international guidelines, a proposal for national harmonization of urine cut-offs for the most common set of drugs of abuse is presented.

Process for fabricating doped zinc oxide microsphere gel

DOEpatents

Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

1991-01-01

A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

Designing in vivo concentration gradients with discrete controlled release: a computational model

NASA Astrophysics Data System (ADS)

Walker, Edgar Y.; Barbour, Dennis L.

2010-08-01

One promising neurorehabilitation therapy involves presenting neurotrophins directly into the brain to induce growth of new neural connections. The precise control of neurotrophin concentration gradients deep within neural tissue that would be necessary for such a therapy is not currently possible, however. Here we evaluate the theoretical potential of a novel method of drug delivery, discrete controlled release (DCR), to control effective neurotrophin concentration gradients in an isotropic region of neocortex. We do so by constructing computational models of neurotrophin concentration profiles resulting from discrete release locations into the cortex and then optimizing their design for uniform concentration gradients. The resulting model indicates that by rationally selecting initial neurotrophin concentrations for drug-releasing electrode coatings in a square 16-electrode array, nearly uniform concentration gradients (i.e. planar concentration profiles) from one edge of the electrode array to the other should be obtainable. DCR therefore represents a promising new method of precisely directing neuronal growth in vivo over a wider spatial profile than would be possible with single release points.

Effects of C and Si on strain aging of strain-based API X60 pipeline steels

NASA Astrophysics Data System (ADS)

Sung, Hyo Kyung; Lee, Dong Ho; Lee, Sunghak; Lee, Byeong-Joo; Hong, Seung-Pyo; Kim, Young-Woon; Yoo, Jang Yong; Hwang, Byoungchul; Shin, Sang Yong

2017-05-01

Four types of strain-based API X60 pipeline steels were fabricated by varying the C and Si contents, and the effects of C and Si on strain aging were investigated. The 0.05 wt% C steels consisted mainly of polygonal ferrite (PF), whereas the 0.08 wt% C steels consisted of acicular ferrite (AF). The volume fraction of AF increased with increasing C content because C is an austenite stabilizer element. The volume fractions of bainitic ferrite (BF) of the 0.15 wt% Si steels were higher than those of the 0.25 wt% Si steels, whereas the volume fractions of the secondary phases were lower. From the tensile properties before and after the aging process of the strainbased API X60 pipeline steels, the yield strength increased and the uniform and total elongation decreased, which is the strain aging effect. The strain aging effect in the strain-based API X60 pipeline steels was minimized when the volume fraction of AF was increased and secondary phases were distributed uniformly. On the other hand, an excessively high C content formed fine precipitates, and the strain aging effect occurred because of the interactions among dislocations and fine precipitates.

Preservative-free triamcinolone acetonide suspension developed for intravitreal injection.

PubMed

Bitter, Christoph; Suter, Katja; Figueiredo, Verena; Pruente, Christian; Hatz, Katja; Surber, Christian

2008-02-01

All commercially available triamcinolone acetonide (TACA) suspensions, used for intravitreal treatment, contain retinal toxic vehicles (e.g., benzyl alcohol, solubilizer). Our aim was to find a convenient and reproducible method to compound a completely preservative-free TACA suspension, adapted to the intraocular physiology, with consistent quality (i.e., proven sterility and stability, constant content and dose uniformity, defined particle size, and 1 year shelf life). We evaluated two published (Membrane-filter, Centrifugation) and a newly developed method (Direct Suspending) to compound TACA suspensions for intravitreal injection. Parameters as TACA content (HPLC), particle size (microscopy and laser spectrometry), sterility, and bacterial endotoxins were assessed. Stability testing (at room temperature and 40 degrees C) was performed: color and homogeneity (visually), particle size (microscopically), TACA content and dose uniformity (HPLC) were analyzed according to International Conference on Harmonisation guidelines. Contrary to the known methods, the direct suspending method is convenient, provides a TACA suspension, which fulfills all compendial requirements, and has a 2-year shelf life. We developed a simple, reproducible method to compound stable, completely preservative-free TACA suspensions with a reasonable shelf-life, which enables to study the effect of intravitreal TACA--not biased by varying doses and toxic compounds or their residues.

Consumer perceptions of prescription drug websites: a pilot study.

PubMed

Wymer, Walter

2010-04-01

Consumer perceptions of the information content contained on prescription drug websites was of interest in this investigation. Twenty branded prescription drugs were selected because they were evaluated as being poor consumer choices for safety reasons or because better alternatives existed. Study participants visited each of 20 websites for the selected drugs, and then they answered a series of questions for each website, in order to evaluate each website's information content. Participants, without knowing the selected prescription drugs were selected because they were problematic, reported that the drug company information was complete, fully presenting benefit and risk information, without being false or misleading in any respect. Pricing information was generally not provided by drug companies. Alternative medicines, treatments, and behavioral approaches for dealing with an illness or health condition were generally not part of the information provided by drug companies. Public policy implications are also discussed.

Thinking outside the medicine cabinet: a comparative content analysis of direct-to-consumer advertisements for prescription drug treatments.

PubMed

McKeever, Robert

2014-01-01

This study content analyzed online direct-to-consumer advertisements (DTCA) for prescription drug treatments to explore whether ads for prescription treatments for psychiatric conditions, which are commonly untreated, differ from other drug advertisements. Coded variables included the presence of interactive technological components, use of promotional incentives, and the social contexts portrayed in images shown on each site. Statistical analysis revealed ads for psychiatric medications contained fewer interactive website features, financial incentives, and calls to action than other types of prescription drug advertisements. Implications for health communication researchers are discussed.

PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties.

PubMed

Avgoustakis, K; Beletsi, A; Panagi, Z; Klepetsanis, P; Karydas, A G; Ithakissios, D S

2002-02-19

The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB/c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and/or targeting of cisplatin.

48 CFR 923.405 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENVIRONMENT, CONSERVATION, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Use of Recovered Materials 923.405... recommended percentage of recovered/recycled content or range of content contained in the Recovered Materials... recovered/recycled content or range of content. Acquisition of a product with recycled content exceeding the...

Construction of dual-functional polymer nanomaterials with near-infrared fluorescence imaging and polymer prodrug by RAFT-mediated aqueous dispersion polymerization.

PubMed

Tian, Chun; Niu, Jinyun; Wei, Xuerui; Xu, Yujie; Zhang, Lifen; Cheng, Zhenping; Zhu, Xiulin

2018-05-31

The performance of functional polymer nanomaterials is a vigorously discussed topic in polymer science. We devoted ourselves to investigating polymer nanomaterials based on near-infrared (NIR) fluorescence imaging and polymer prodrug in this study. Aza-boron dipyrromethene (BODIPY) is an important organic dye, having characteristics such as environmental resistance, light resistance, high molar extinction coefficient, and fluorescence quantum yield. We incorporated it into our target monomer, which can be polymerized without changing its parent structure in a polar solvent and copolymerized with water-soluble monomer to improve the solubility of the dye in an aqueous solution. At the same time, the hydrophobic drug camptothecin (CPT) was designed as a prodrug monomer, and the polymeric nanoparticles (NPs) with NIR fluorescence imaging and prodrug were synthesized in situ in reversible addition-fragmentation chain transfer (RAFT)-mediated aqueous dispersion polymerization. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed the final uniform size of the dual-functional polymeric NPs morphology. The dual-functional polymeric NPs had a strong absorption and emission signal in the NIR region (>650 nm) based on the fluorescence tests. In consideration of the long-term biological toxicity, confocal laser scanning microscopy (CLSM) results indicated that the dual-functional NPs with controlled drug content exhibited effective capability of killing HeLa cells. In addition, in vivo imaging of the dual-functional NPs was observed in real time, and the fluorescent signals clearly demonstrated the dynamic process of prodrug transfer.

78 FR 951 - Accessible Medical Device Labeling in a Standard Content and Format Public Workshop; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1205] Accessible Medical Device Labeling in a Standard Content and Format Public Workshop; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop; request for comments...

78 FR 6825 - Accessible Medical Device Labeling in a Standard Content and Format Public Workshop; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1205] Accessible Medical Device Labeling in a Standard Content and Format Public Workshop; Request for Comments; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop; request for comments...

Drug Information Training and Experience at U.S. Schools of Pharmacy.

ERIC Educational Resources Information Center

Davis, Sharon K.; Krucke, Lynn B.

1994-01-01

A survey of 56 pharmacy schools gathered information on current content of drug information courses and clerkships and plans to change training methods as the Doctor of Pharmacy becomes the sole entry-level degree. Some schools will modify course or clerkship content, by omitting or shifting objectives within the curriculum. (Author/MSE)

Content and retention evaluation of an audiovisual patient-education program on bronchodilators.

PubMed

Darr, M S; Self, T H; Ryan, M R; Vanderbush, R E; Boswell, R L

1981-05-01

A study was conducted to: (1) evaluate the effect of a slide-tape program on patients' short-term and long-term knowledge about their bronchodilator medications; and (2) determine it any differences exist in learning or retention patterns for different content areas of drug information. The knowledge of 30 patients was measured using a randomized sequence of three comparable 15-question tests. The first test was given before the slide-tape program was presented, the second test within 24 hours, and the last test one to six months (mean = 2.8 months) later. Scores attained on the first posttest were significantly higher (p less than 0.001) than pretest scores. Learning differences among drug-information-content areas were not evidenced on the first posttest. No significant difference was demonstrated between scores on pretest and last posttest (p = 0.100). However, retention patterns among content areas were found to differ significantly (p less than 0.05). Carefully designed audiovisual programs can impart drug information to patients. Medication counseling should be repeated at appropriate opportunities because patients lose drug knowledge over time.

High loading uranium fuel plate

DOEpatents

Wiencek, Thomas C.; Domagala, Robert F.; Thresh, Henry R.

1990-01-01

Two embodiments of a high uranium fuel plate are disclosed which contain a meat comprising structured uranium compound confined between a pair of diffusion bonded ductile metal cladding plates uniformly covering the meat, the meat having a uniform high fuel loading comprising a content of uranium compound greater than about 45 Vol. % at a porosity not greater than about 10 Vol. %. In a first embodiment, the meat is a plurality of parallel wires of uranium compound. In a second embodiment, the meat is a dispersion compact containing uranium compound. The fuel plates are fabricated by a hot isostatic pressing process.

Regular expansion solutions for small Peclet number heat or mass transfer in concentrated two-phase particulate systems

NASA Technical Reports Server (NTRS)

Yaron, I.

1974-01-01

Steady state heat or mass transfer in concentrated ensembles of drops, bubbles or solid spheres in uniform, slow viscous motion, is investigated. Convective effects at small Peclet numbers are taken into account by expanding the nondimensional temperature or concentration in powers of the Peclet number. Uniformly valid solutions are obtained, which reflect the effects of dispersed phase content and rate of internal circulation within the fluid particles. The dependence of the range of Peclet and Reynolds numbers, for which regular expansions are valid, on particle concentration is discussed.

21 CFR 58.31 - Testing facility management.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testing facility management. 58.31 Section 58.31... management. For each nonclinical laboratory study, testing facility management shall: (a) Designate a study... appropriately tested for identity, strength, purity, stability, and uniformity, as applicable. (e) Assure that...

FIELD SAMPLING OF RESIDUAL AVIATION GASOLINE IN SANDY SOIL

EPA Science Inventory

Two complimentary field sampling methods for the determination of residual aviation gasoline content in the contaminated capillary fringe of a fine, uniform, sandy soil were investigated. The first method featured filed extrusion of core barrels into pint size Mason jars, while ...

CALIPSO V1.00 L3 IceCloud Formal Release Announcement

Atmospheric Science Data Center

2018-06-13

... The Atmospheric Science Data Center (ASDC) at NASA Langley Research Center in collaboration with the CALIPSO mission team announces the ... distributions of ice cloud extinction coefficients and ice water content histograms on a uniform spatial grid.  All parameters are ...

Gravitational wave content and stability of uniformly, rotating, triaxial neutron stars in general relativity.

PubMed

Tsokaros, Antonios; Ruiz, Milton; Paschalidis, Vasileios; Shapiro, Stuart L; Baiotti, Luca; Uryū, Kōji

2017-06-15

Targets for ground-based gravitational wave interferometers include continuous, quasiperiodic sources of gravitational radiation, such as isolated, spinning neutron stars. In this work, we perform evolution simulations of uniformly rotating, triaxially deformed stars, the compressible analogs in general relativity of incompressible, Newtonian Jacobi ellipsoids. We investigate their stability and gravitational wave emission. We employ five models, both normal and supramassive, and track their evolution with different grid setups and resolutions, as well as with two different evolution codes. We find that all models are dynamically stable and produce a strain that is approximately one-tenth the average value of a merging binary system. We track their secular evolution and find that all our stars evolve toward axisymmetry, maintaining their uniform rotation, rotational kinetic energy, and angular momentum profiles while losing their triaxiality.

Plasma-sprayed self-lubricating coatings

NASA Technical Reports Server (NTRS)

Nakamura, H. H.; Logan, W. R.; Harada, Y.

1982-01-01

One of the most important criterion for acceptable commercial application of a multiple phase composition is uniformity and reproducibility. This means that the performance characteristics of the coat - e.g., its lubricating properties, bond strength to the substrate, and thermal properties - can be readily predicted to give a desired performance. The improvement of uniformity and reproducibility of the coats, the oxidation behavior at three temperature ranges, the effect of bond coat and the effect of preheat treatment as measured by adhesive strength tests, coating examination procedures, and physical property measurements were studied. The following modifications improved the uniformity and reproducibility: (1) changes and closer control in the particle size range of the raw materials used, (2) increasing the binder content from 3.2% to 4.1% (dried weight), and (3) analytical processing procedures using step by step checking to assure consistency.

Effect of Graphitic Content on Carbon Supported Catalyst Performance

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

Patel, Anant; Artyushkova, Kateryna; Atanassov, Plamen

2011-07-01

The effect of graphitic content on carbon supported platinum catalysts was investigated in order to investigate its influence on catalyst performance. Four catalysts of varying surface areas and graphitic content were analyzed using XPS, HREELS, and tested using RDE experiments. The catalysts were also heat treated at 150oC and 100%RH as means to uniformly age them. The heat treated samples were analyzed using the same methods to determine what changes had occurred due to this aging process. When compared to the BOL catalysts, heat treated catalysts displayed increased graphitic carbon and platinum metalic content, however they also showed depressed catalyticmore » activity. The primary cause is still under investigation, though it is believed to be related to loss of amorphous carbon content.« less

Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems.

PubMed

Berger, D; Nastase, S; Mitran, R A; Petrescu, M; Vasile, E; Matei, C; Negreanu-Pirjol, T

2016-08-30

Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development. Copyright © 2016 Elsevier B.V. All rights reserved.

The colorimetric analysis of anti-tuberculosis fixed-dose combination tablets and capsules.

PubMed

Ellard, G A

1999-11-01

The perceived need to demonstrate whether or not the actual amounts of rifampicin, isoniazid and pyrazinamide in fixed-dose combination tablets or capsules correspond to their stated drug contents. To adapt specific, robust and simple colorimetric methods that have been previously applied to measuring plasma and urinary rifampicin, isoniazid, pyrazinamide and ethambutol concentrations to estimate tablet and capsule drug contents. The methods were applied to the analysis of 14 commercially manufactured fixed-dose combinations: two capsule and three tablet formulations containing rifampicin and isoniazid; seven tablet formulations containing rifampicin, isoniazid and pyrazinamide; and two tablet formulations containing rifampicin, isoniazid, pyrazinamide and ethambutol. All the combined formulations contained near to their stated drug contents. Replicate analyses confirmed the excellent precision of the drug analyses. Such methods are not only rapid to perform but should be practical in many Third World situations with relatively modest laboratory facilities.

Pore-scale modeling of Capillary Penetration of Wetting Liquid into 3D Fibrous Media: A Critical Examination of Equivalent Capillary Concept

NASA Astrophysics Data System (ADS)

Palakurthi, Nikhil Kumar; Ghia, Urmila; Comer, Ken

2013-11-01

Capillary penetration of liquid through fibrous porous media is important in many applications such as printing, drug delivery patches, sanitary wipes, and performance fabrics. Historically, capillary transport (with a distinct liquid propagating front) in porous media is modeled using capillary-bundle theory. However, it is not clear if the capillary model (Washburn equation) describes the fluid transport in porous media accurately, as it assumes uniformity of pore sizes in the porous medium. The present work investigates the limitations of the applicability of the capillary model by studying liquid penetration through virtual fibrous media with uniform and non-uniform pore-sizes. For the non-uniform-pore fibrous medium, the effective capillary radius of the fibrous medium was estimated from the pore-size distribution curve. Liquid penetration into the 3D virtual fibrous medium at micro-scale was simulated using OpenFOAM, and the numerical results were compared with the Washburn-equation capillary-model predictions. Preliminary results show that the Washburn equation over-predicts the height rise in the early stages (purely inertial and visco-inertial stages) of capillary transport.

Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content.

PubMed

Chrubasik-Hausmann, Sigrun; Vlachojannis, Julia; McLachlan, Andrew J

2018-02-07

The aim of this study was to review herb-drug interaction studies with St John's wort (Hypericum perforatum L.) with a focus on the hyperforin content of the extracts used in these studies. PUBMED was systematically searched to identify studies describing pharmacokinetic interactions involving St John's wort. Data on study design and the St John's wort extract or product were gathered to extract hyperforin content and daily dose used in interaction studies. This analysis demonstrates that significant herb-drug interactions (resulting in a substantial change in systemic exposure) with St John's wort products were associated with hyperforin daily dosage. Products that had a daily dose of <1 mg hyperforin were less likely to be associated with major interaction for drugs that were CYP3A4 or p-glycoprotein substrates. Although a risk of interactions cannot be excluded even for low-dose hyperforin St. John's wort extracts, the use of products that result in a dose of not more than 1 mg hyperforin per day is recommended to minimise the risk of interactions. This review highlights that the significance of herb-drug interactions with St John's wort is influenced by the nature of the herbal medicines product, particularly the hyperforin content. © 2018 Royal Pharmaceutical Society.

In vitro analysis of the properties of Beiqishen tea.

PubMed

Blázovics, A; Szentmihályi, K; Lugasi, A; Balázs, A; Hagymási, K; Bányai, E; Then, M; Rapavi, E; Héthelyi, E

2003-10-01

Chinese Beiqishen tea was studied in an in vitro test system. Phytochemical screening, trace element analysis, and the analysis of antioxidant properties were carried out. Characteristic constituents were determined by chromatographic (capillary gas chromatography and GCQ Ion Trap mass spectrometry) and spectrometric (ultraviolet and UV-VIS) methods. Element concentrations were determined by inductively coupled plasma optical emission spectrometry. Antioxidant capacity was studied by spectrophotometric and luminometric techniques using a Berthold Lumat 9501 luminometer. Hydrogen-donating activity, reducing power, and total scavenger capacity were measured. Total polyphenol content was 20.77 +/- 0.52 g/100 g of drug; total flavonoid content was 0.485 +/- 0.036 g/100 g of drug; and tannin content was 9.063 +/- 0.782 g/100 g of drug. Caffeine content was 1.08 mg/100 g of drug. Essential oils were identified by gas chromatography: (+)-limonene (21%), p-cymene (1.7%), estragol (3.2%), beta-ocimene (1.4%), and thymol (2.6%). Metallic ion analysis showed significantly high concentrations of Al, As, Ba, Cr, Cu, Fe, Mn, Ni, and Ti in the drug. Antioxidant and scavenger properties were identified as a function of concentration. The tea infusion contained some non-desirable trace elements and caffeine in addition to polyphenols and tannins in high concentrations. Therefore, the consumption of this tea may involve risks.

Formulation development and evaluation of metformin chewing gum with bitter taste masking

PubMed Central

Mostafavi, Sayed Abolfazl; Varshosaz, Jaleh; Arabian, Saber

2014-01-01

Background: Medicated gums are intended to be chewed and act either locally, absorbed via the buccal mucosa or swallowed with saliva. We prepared the metformin gum to overcome its side effects including vomiting, diarrhea, and abdomen discomfort. Furthermore, it could be useful for those who have swallowing problems. Materials and Methods: Metformin hydrochloride (250 mg) with suitable sweeteners was mixed manually for 5 min. This mixture was spray dried, freeze dried, or directly mixed with chewing gum base. Glycerin, xylitol, and menthol were added and the produced paste was kept in the freezer for 2 h to be stable. As the metformin shows bitter taste, we tried to mask this unpleasant taste with using different methods explained. The releasing pattern was evaluated by using a mechanical chewing machine. The best formulation with the optimized releasing pattern, suitable physicochemical properties and pleasant taste were selected. Content uniformity, releasing percent, and other physicochemical properties were identified as well. Taste, flavor, and appearance characteristics were evaluated by using a self-made questionnaire based on the hedonic test method. Results: The chewing gum dosage content was about 86.2%. The release rate of metformin chewing gum was about 70% after 5 min of mastication. Masking the bitter taste of drug was achieved by using acesulfame-isomalt as sweeteners and prepared it by freeze drying equipment. Conclusion: Metfornin chewing gum had suitable appearance and appropriate invitro characteristics that fallow the pharmacopeia suggestions. This chewable gum showed bitterness suppression with a suitable release rate. PMID:24800181

Development of a chromatographic method with multi-criteria decision making design for simultaneous determination of nifedipine and atenolol in content uniformity testing.

PubMed

Ahmed, Sameh; Alqurshi, Abdulmalik; Mohamed, Abdel-Maaboud Ismail

2018-07-01

A new robust and reliable high-performance liquid chromatography (HPLC) method with multi-criteria decision making (MCDM) approach was developed to allow simultaneous quantification of atenolol (ATN) and nifedipine (NFD) in content uniformity testing. Felodipine (FLD) was used as an internal standard (I.S.) in this study. A novel marriage between a new interactive response optimizer and a HPLC method was suggested for multiple response optimizations of target responses. An interactive response optimizer was used as a decision and prediction tool for the optimal settings of target responses, according to specified criteria, based on Derringer's desirability. Four independent variables were considered in this study: Acetonitrile%, buffer pH and concentration along with column temperature. Eight responses were optimized: retention times of ATN, NFD, and FLD, resolutions between ATN/NFD and NFD/FLD, and plate numbers for ATN, NFD, and FLD. Multiple regression analysis was applied in order to scan the influences of the most significant variables for the regression models. The experimental design was set to give minimum retention times, maximum resolution and plate numbers. The interactive response optimizer allowed prediction of optimum conditions according to these criteria with a good composite desirability value of 0.98156. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines with the aid of the experimental design. The developed MCDM-HPLC method showed superior robustness and resolution in short analysis time allowing successful simultaneous content uniformity testing of ATN and NFD in marketed capsules. The current work presents an interactive response optimizer as an efficient platform to optimize, predict responses, and validate HPLC methodology with tolerable design space for assay in quality control laboratories. Copyright © 2018 Elsevier B.V. All rights reserved.

Multivariate figures of merit (FOM) investigation on the effect of instrument parameters on a Fourier transform-near infrared spectroscopy (FT-NIRS) based content uniformity method on core tablets.

PubMed

Doddridge, Greg D; Shi, Zhenqi

2015-01-01

Since near infrared spectroscopy (NIRS) was introduced to the pharmaceutical industry, efforts have been spent to leverage the power of chemometrics to extract out the best possible signal to correlate with the analyte of the interest. In contrast, only a few studies addressed the potential impact of instrument parameters, such as resolution and co-adds (i.e., the number of averaged replicate spectra), on the method performance of error statistics. In this study, a holistic approach was used to evaluate the effect of the instrument parameters of a FT-NIR spectrometer on the performance of a content uniformity method with respect to a list of figures of merit. The figures of merit included error statistics, signal-to-noise ratio (S/N), sensitivity, analytical sensitivity, effective resolution, selectivity, limit of detection (LOD), and noise. A Bruker MPA FT-NIR spectrometer was used for the investigation of an experimental design in terms of resolution (4 cm(-1) and 32 cm(-1)) and co-adds (256 and 16) plus a center point at 8 cm(-1) and 32 co-adds. Given the balance among underlying chemistry, instrument parameters, chemometrics, and measurement time, 8 cm(-1) and 32 co-adds in combination with appropriate 2nd derivative preprocessing was found to fit best for the intended purpose as a content uniformity method. The considerations for optimizing both instrument parameters and chemometrics were proposed and discussed in order to maximize the method performance for its intended purpose for future NIRS method development in R&D. Copyright © 2014 Elsevier B.V. All rights reserved.

The usefulness and scientific accuracy of private sector Arabic language patient drug information leaflets.

PubMed

Sukkari, Sana R; Al Humaidan, Abdullah S; Sasich, Larry D

2012-07-01

Inadequate access to useful scientifically accurate patient information is a major cause of the inappropriate use of drugs resulting in serious personal injury and related costs to the health care system. The definition of useful scientifically accurate patient information for prescription drugs was accepted by the US Secretary of the Department of Health and Human Services in 1996 as that derived from or consistent with the US FDA approved professional product label for a drug. Previous quality content studies found that English language patient drug information leaflets distributed by US pharmacies failed to meet minimum criteria defining useful and scientifically accurate information. Evaluation forms containing the explicit elements that define useful scientifically accurate information for three drugs with known serious adverse drug reactions were created based on the current US FDA approved professional product labels. The Arabic language patient drug information leaflets for celecoxib, paroxetine, and lamotrigine were obtained locally and evaluated using a methodology similar to that used in previous quality content patient drug information studies in the US. The Arabic leaflets failed to meet the definition of useful scientifically accurate information. The celecoxib leaflet contained 30% of the required information and the paroxetine and lamotrigine leaflets contained 24% and 20%, respectively. There are several limitations to this study. The Arabic leaflets from only one commercial North American vendor were evaluated and the evaluation included a limited number of drugs. A larger study is necessary to be able to generalize these results. The study results are consistent with those of previous quality content studies of commercially available English patient drug information leaflets. The results have important implications for patients as access to a reliable source of drug information may prevent harm or limit the suffering from serious adverse drug reactions.

Uniform, dense arrays of vertically aligned, large-diameter single-walled carbon nanotubes.

PubMed

Han, Zhao Jun; Ostrikov, Kostya

2012-04-04

Precisely controlled reactive chemical vapor synthesis of highly uniform, dense arrays of vertically aligned single-walled carbon nanotubes (SWCNTs) using tailored trilayered Fe/Al(2)O(3)/SiO(2) catalyst is demonstrated. More than 90% population of thick nanotubes (>3 nm in diameter) can be produced by tailoring the thickness and microstructure of the secondary catalyst supporting SiO(2) layer, which is commonly overlooked. The proposed model based on the atomic force microanalysis suggests that this tailoring leads to uniform and dense arrays of relatively large Fe catalyst nanoparticles on which the thick SWCNTs nucleate, while small nanotubes and amorphous carbon are effectively etched away. Our results resolve a persistent issue of selective (while avoiding multiwalled nanotubes and other carbon nanostructures) synthesis of thick vertically aligned SWCNTs whose easily switchable thickness-dependent electronic properties enable advanced applications in nanoelectronic, energy, drug delivery, and membrane technologies.

Final Report One-Twelfth-Scale Mixing Experiments to Characterize Double-Shell Tank Slurry Uniformity

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

Bamberger, Judith A.; Liljegren, Lucia M.; Enderlin, Carl W.

The objectives of these 1/12-scale scoping experiments were to: Determine which of the dimensionless parameters discussed in Bamberger and Liljegren (1994) affect the maximum concentration that can be suspended during jet mixer pump operation in the full-scale double-shell tanks; Develop empirical correlations to predict the nozzle velocity required for jet mixer pumps to suspend the contents of full-scale double-shell tanks; Apply the models to predict the nozzle velocity required to suspend the contents of Tank 241 AZ-101; Obtain experimental concentration data to compare with the TEMPEST( )(Trent and Eyler 1989) computational modeling predictions to guide further code development; Analyze themore » effects of changing nozzle diameter on exit velocity (U0) and U0D0 (the product of the exit velocity and nozzle diameter) required to suspend the contents of a tank. The scoping study experimentally evaluated uniformity in a 1/12-scale experiment varying the Reynolds number, Froude number, and gravitational settling parameter space. The initial matrix specified only tests at 100% U0D0 and 25% U0D0. After initial tests were conducted with small diameter, low viscosity simulant this matrix was revised to allow evaluation of a broader range of U0D0s. The revised matrix included full factorial test between 100% and 50% U0D0 and two half-factorial tests at 75% and 25% U0D0. Adding points at 75% U0D0 and 50% U0D0 allowed evaluation curvature. Eliminating points at 25% U0D0 decreased the testing time by several weeks. Test conditions were achieved by varying the simulant viscosity, the mean particle size, and the jet nozzle exit velocity. Concentration measurements at sampling locations throughout the tank were used to assess the degree of uniformity achieved during each test. Concentration data was obtained using a real time ultrasonic attenuation probe and discrete batch samples. The undissolved solids concentration at these locations was analyzed to determine whether the tank contents were uniform (< ±10% variation about mean) or nonuniform (> ±10% variation about mean) in concentration. Concentration inhomogeneity was modeled as a function of dimensionless groups. The two parameters that best describe the maximum solids volume fraction that can be suspended in a double-shell tank were found to be 1) the Froude number (Fr) based on nozzle velocity (U0) and tank contents level (H) and 2) the dimensionless particle size (dp/D0). The dependence on the Reynolds number (Re) does not appear to be statistically significant.« less

Visual properties and memorising scenes: Effects of image-space sparseness and uniformity.

PubMed

Lukavský, Jiří; Děchtěrenko, Filip

2017-10-01

Previous studies have demonstrated that humans have a remarkable capacity to memorise a large number of scenes. The research on memorability has shown that memory performance can be predicted by the content of an image. We explored how remembering an image is affected by the image properties within the context of the reference set, including the extent to which it is different from its neighbours (image-space sparseness) and if it belongs to the same category as its neighbours (uniformity). We used a reference set of 2,048 scenes (64 categories), evaluated pairwise scene similarity using deep features from a pretrained convolutional neural network (CNN), and calculated the image-space sparseness and uniformity for each image. We ran three memory experiments, varying the memory workload with experiment length and colour/greyscale presentation. We measured the sensitivity and criterion value changes as a function of image-space sparseness and uniformity. Across all three experiments, we found separate effects of 1) sparseness on memory sensitivity, and 2) uniformity on the recognition criterion. People better remembered (and correctly rejected) images that were more separated from others. People tended to make more false alarms and fewer miss errors in images from categorically uniform portions of the image-space. We propose that both image-space properties affect human decisions when recognising images. Additionally, we found that colour presentation did not yield better memory performance over grayscale images.