Academic literature on the topic 'Sustained release tablets'

The use of antiretroviral (ARV) agents in the management of HIV/AIDS has significantly improved the lifestyle and wellbeing of patients. Despite the success that has been achieved with the use of ARV therapy, the occurrence of adverse effects and unpredictable bioavailability associated with most of these drugs remains a major concern. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is used in combination with other ARV compounds for the treatment of HIV-1 infections. It is also used for the prevention of mother to child transmission of the HIV-1 virus. NVP is a Biopharmaceutics Classification System (BCS) Class II compound. Although NVP exhibits good oral absorption, it induces self-metabolism leading to low and sometimes unpredictable bioavailability. NVP is commercially available as an immediate release and extended release dosage form, viz., Viramune® XR. Formulation of a generic sustained release (SR) dosage form for once daily dosing would result in delivery of constant amount of the drug to the circulation, reduce dose related adverse effects, improve patient compliance to medication and reduce the costs of therapy. A simple RP-HPLC method was developed and optimised using a central composite design approach. The method was validated using ICH guidelines and was found to be linear, precise, specific and accurate for the analysis of NVP both in bulk and dosage forms. Direct compression was used as the method of tablet manufacture. Different polymers were assessed for suitability as rate retarding polymers and included Methocel® K4M, Carbopol® 71G NF and Eudragit® RSPO. Powder blends were assessed for flow properties using the angle of repose, bulk and tapped density, Carr’s Compressibility index and Hausner’s ratio. The traditional approach of changing the amount of polymers and diluents systematically to achieve a desired NVP release profile was used for the development of a preliminary formulation. Response surface methodology was used for the optimisation of the formulation using a Box-Behnken quadratic design. Physical characteristics of the tablets such as thickness, weight, hardness, tensile strength and friability were assessed and the tablets passed Pharmacopoeial testing. NVP assay and content uniformity were assessed using a validated RP-HPLC method. Initially, USP Apparatus 2 was used to study NVP release over a 24 hour period and subsequently dissolution studies were performed using USP Apparatus 3 as it can be used to simulate GIT conditions. The dissolution profiles generated were used to determine the agitation rate for USP Apparatus 3 that would be equivalent to an agitation rate of 50 rpm when using USP Apparatus 2. The effect of the mesh screen pore size, buffer molarity strength and concentration of surfactant on NVP release were also investigated in order to select discriminatory dissolution test conditions for the test formulation. Dissolution profiles were compared to those of the commercially available Viramune® XR using the FDA recommended difference (f1) and similarity (f2) factors. The calculated values for f1 and f2 revealed that the dissolution profile for the optimised formulation that was identified was statistically similar to Viramune® XR. In vitro release data were fitted to different kinetic models to study the release kinetics of NVP. The overall mechanism of NVP release was best described using the Korsmeyer-Peppas diffusion exponent value, n. NVP release was found to be anomalous, implying that the release was influenced by a combination of diffusion, swelling and polymer chain relaxation. The Hixson-Crowell model revealed that there was constant change in surface area of the dosage form suggesting that erosion and swelling were significant factors affecting NVP release from the hydrophilic matrix technology. The release kinetics data were also used to design the optimised formulation. Tablets manufactured using the optimised formulation were subjected to water uptake and erosion studies and the results revealed that swelling and erosion occur simultaneously. The effects of pH and molarity on the swelling and erosion of the tablets were also investigated. The data suggest that increase in pH resulted in a slight increase in swelling while an increase in molarity did not have a significant effect on swelling. The change in pH did not have a significant effect on erosion while an increase in molarity strength resulted in a decrease in matrix erosion. The effect of HPMC grade on swelling, erosion and NVP release revealed that the grade of HPMC used had a significant effect on NVP release, with the release rate decreasing, swelling increasing and erosion decreasing as the viscosity of the HPMC grade increased. The effect of the particle size of MCC on NVP release was also studied by manufacturing tablets containing different grades of MCC and these studies revealed that particle size did not appear to have a significant effect on NVP release. Similarly the use of different types of lactose did not appear to have a significant impact on NVP release. In conclusion a sustained release NVP tablet formulation that has the potential for further development and optimisation has been developed, assessed and manufactured successfully and has been shown to exhibit similar dissolution behaviour to Viramune® XR, a commercially available NVP extended release product.

Beta blockers are commonly prescribed for the chronic treatment of hypertension, one of the most prolific disease states worldwide. The beta blockers selected for this study include acebutolol hydrochloride, labetalol hydrochloride, metoprolol tartrate oxprenolol hydrochloride and propranolol hydrochloride. All of these compounds have a short elimination half-life, necessitating multiple dose per day regimens and therefore the development of sustained release dosage forms incorporating these agents was considered beneficial in terms of extending the dosing interval, with the aim of improving patient compliance and subsequent therapeutic outcomes. Preformulation studies that were conducted included moisture content analysis by Karl Fischer titration, and DSC, a method used to predict potential interactions between the drugs and tablet excipients. Tablets were manufactured by both wet granulation and direct compression techniques, and the resultant drug release characteristics were evaluated using the USP Apparatus 3(BIO.DIS). A validated isocratic HPLC method, capable of separating the five drug candidates simultaneously, was developed and used for the analysis of drug samples. Tablet quality was assessed using analyses that included the physical assessment of weight, diameter, thickness, hardness and friability, as well as content uniformity of tablets, before and after dissolution testing. Direct compression tablet formulations containing each of the five beta blockers were successfully adapted from a prototype wet granulation matrix tablet containing metoprolol tartrate, and various formulation variables were investigated to establish,their effect on the rate and extent of drug release from these tablets. The grade and quantity of ethylcellulose used in the wet granulation and direct compression formulae influenced the release rate of some drug candidates. In addition, an alternative formulation method, involving freeze-drying of the drug with an ethylcellulose dispersion, was shown to have potential for altering release rates further. Anti-frictional agents, talc and colloidal silicon dioxide, did not affect drug release from these matrices,however, they affected the physical character:istics such as tablet weight and thickness, of the resultant tablets. All of the matrix tablets formulated were shown to release drug according to square root of time kinetics, in a sustained manner over a 22 hour period.

<p> The ability of chitosan and tripolyphosphate to form an ionic crosslinked material and its effectiveness in sustained release formulations has been reported. However, key issues commonly observed with these formulations include inefficiencies and inaccuracies in the drug loading as well as an inability to achieve complete release of drug. Acetaminophen, as a model drug, was added to various chitosan-tripolyphosphate crosslinked powders to assess the sustained release characteristics when drug is added extragranularly as opposed to during the crosslinking process, which is the most common procedure for drug addition in prior literature. The influence of various process and formulation variables including chitosan concentration, chitosan:tripolyphosphate ratio, temperature, ionic strength, and pH was assessed. Design of experiments allowed the identification of factors and two factor interactions that have significant effects on particle size and size distribution, yield, zeta potential, true density, and drug release. Statistical model equations were successfully used to manufacture optimized chitosan-tripolyphosphate crosslinked powders with various properties for further evaluation. Analysis of the compressibility of the optimized powders revealed that the crosslinked powders had enhanced compression properties when compared to chitosan powder. Environmental scanning electron microscopy revealed a correlation between the rigidity and density of the powders and corresponding capabilities for enhanced sustained release. Analysis of the moisture sorption and desorption isotherms from dynamic vapor sorption analysis revealed various types and levels of water present and a correlation between the quantity of water internally absorbed during sorption and desorption and sustained release capability. Chitosan-tripolyphosphate crosslinked powder can be manufactured with optimized properties that allow desired sustained drug release profiles while simultaneously serving as the primary diluent for solid oral dosage forms.</p><p>

Parmi toutes les voies d’administration, la voie orale a toujours suscité un grand intérêt. Les formes prises par voie orale présentent une grande facilité d’administration pour le patient, tandis que pour les chercheurs, la physiologie du système gastro-intestinal peut être facilement modélisable. Malheureusement, son importante variabilité, liée principalement au temps de vidange gastrique, peut conduire à une mauvaise reproductibilité des effets thérapeutiques et à une diminution de la biodisponibilité. Ce problème est surtout rencontré dans le cas des principes actifs présentant une fenêtre d’absorption étroite au niveau de l’intestin supérieur [Deshpande et col. 1996]. Une solution a été de développer des formes galéniques à libération prolongée caractérisées par un temps de résidence gastrique accru. Ainsi, le principe actif est libéré progressivement en amont de sa fenêtre d’absorption. Dans cette optique, plusieurs systèmes ont été développés :des formes bioadhésives, expansibles, gonflantes ou à hautes densités [Singh et Kim, 2000]. Mais parmi toutes ces formes, ce sont les systèmes flottants qui semblent offrir la protection la plus efficace contre une vidange gastrique précoce [Moës, 1989]. Seth et Tossounian ont ainsi développé une gélule flottante à libération prolongée, basée sur le gonflement d’un dérivé cellulosique. Etant une forme monolithique, sa vidange gastrique était soumise au phénomène de tout ou rien. De plus, cette forme présentait un inconvénient majeur puisqu’elle était sujette à des fractionnements intra-gastriques, diminuant de ce fait la reproductibilité inter- et intra-individuelle [Seth et Tossounian, 1984]. <p>\<br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished

Les comprimés matriciels hydrophiles sont fréquemment utilisés pour contrôler la libération d’actif dans les formes galéniques à usage oral. Les amidons représentent un choix intéressant pour cette application. En effet, ce sont des matériaux biocompatibles, biodégradables et disponibles à partir de différentes sources végétales. En plus des amidons natifs, les amidons modifiés (AM) ont été beaucoup étudiés pour la formulation des comprimés matriciels à libération prolongée. Les modifications physico-chimiques peuvent être ajustées de manière à correspondre aux propriétés souhaitées pour une application pharmaceutique spécifique. De nombreux scientifiques ont rapportés l'utilisation de ces amidons pour les comprimés à libération contrôlée. Ils ont obtenu des résultats prometteurs montrant la capacité de ces excipients à retarder la libération d’actif dans. Cependant, la plupart des amidons utilisés dans ces études sont généralement produits à l'échelle laboratoire, et peuvent donc présenter des propriétés différentes des AM produits à l’échelle industrielle. Par conséquent, il pourrait être très difficile de transposer la production de ces amidons à l’échelle industrielle sans altérer leurs propriétés caractéristiques. L'objectif principal de ce travail était d'identifier un nouvel excipient à base d'amidon pour contrôler la libération d’actif à partir de comprimés. Ainsi, dans un premier temps, un grand criblage a permis d'étudier différents types d'amidons pour préparer des comprimés de diprohylline par compression directe. L'impact de l'origine botanique des amidons, de la méthode de pré-gélatinisation, du degré et de la nature de réticulation, ainsi que la substitution chimique ont été étudiées et les cinétiques de libération d’actif ont été mesurées. Pour avoir une meilleure compréhension de ces résultats, l’analyse de texture de l’hydrogel formé au contact du milieu de libération, la microscopie optique et électronique à balayage (MEB) ainsi que l’analyse par diffraction des rayons X ont été réalisées. De plus, un « test rapide » a été mis en place pour évaluer le potentiel d'un d'amidon donné à prolonger libération d’actif. Les résultats obtenus sur l'importance du type d'amidon et leur impact sur les cinétiques de libération d’actif des comprimés matriciels peuvent aider à mieux assimiler et optimiser ces systèmes avancés d'administration de médicaments. Dans une deuxième partie, le potentiel du (PREGEFLO® PI10) a été évalué comme agent matriciel pour les comprimés à libération prolongée. Pour ce faire, différents types de comprimés chargés d’actifs ayant une solubilité différente ont été préparés par compression directe. La robustesse de cette matrice a été étudiée dans des milieux de libération très variés. Plusieurs appareils de dissolution ont été utilisés séparément ou combinés avec d'autres machines pour simuler le stress hydrodynamique subi par les comprimés lors de leur passage à travers le tractus gastro-intestinal. Les résultats obtenus ont montré que les profils de libération d’actif à partir du PREGEFLO® PI10 n'étaient pas affectés par toutes les conditions étudiées. Ainsi, le PREGEFLO® PI10 se positionne comme un bon candidat comme polymère de libération prolongée pour la voie orale. Enfin, pour caractériser la distribution d’actif au sein du système matriciel, en particulier dans les régions «sèches» et gonflés après dissolution du comprimé, et examiner comment les distributions spatiales changent au cours du temps, l'imagerie Raman, la MEB, la spectroscopie de rayons X à dispersion d'énergie (EDX) et la cristallographie aux rayons X ont été utilisées sur des comprimés avant et après exposition au tampon. Les cartographies Raman ont confirmé que l’actif est bien piégé dans le noyau du comprimé «sec». Ces observations ont mis en évidence la différence de morphologie entre la région centrale « sèche » et la région dans laquelle la matrice du comprimé a subi un gonflement important<br>Hydrophilic matrix tablets are frequently used to control the drug release from oral dosage forms. Starch-based polymers are interesting matrix former in this respect, due to their biocompatibility, biodegradability, and availability from different plant sources. In addition to native starches, modified starches have been frequently used with various physiochemical modifications, which could be tailored to provide desired properties for a specific pharmaceutical application. Many scientists have reported the use of modified starches as matrix formers for oral controlled release tablets. Numerous starch-based extended release polymers have successfully retarded drug releases. However, most of the starch batches used in those studies are generally produced at a laboratory scale and may therefore present different properties compared to modified starches obtained with industrial scale. Hence, it could be very difficult to scale up the production of these excipients without changing their key features. The major goal of this work was to identify a new excipient, based on starch to control the drug release from direct compressible matrix tablets. Therefore, in a first instance, a large screening allowed to study different types of starches to prepare diprophylline matrix tablets. The effect of the botanical origin of starches, the type of pre-gelatinization method as well as of the degree and type of cross-linking and chemical substitution have been investigated, and the resulting drug release rates from diprophylline-loaded matrix tablets were measured. For a better understanding of these results, texture analysis of the gel-layer, created upon contact with the release medium, optical and scanning electron microscopy (SEM) as well as X- ray powder diffraction analysis were applied. Moreover, a “quick test” has been proposed to evaluate the potential of a particular type of starch to sustain the drug release rate. The obtained results on the importance of the starch type and their influence on the resulting drug release rates from matrix tablets can help for a better understanding and optimization of this type of advanced drug delivery systems. In a second phase, the potential of (PREGEFLO® PI10), has been evaluated as a matrix former for controlled release tablets. Hence, various types of matrix tablets loaded with drugs having different solubility were prepared by direct compression. The robustness of this cross-linked pregelatinized potato starch matrix was investigated in a variety of release media. In addition to that, several types of experimental USP apparatuses were used separately or combined with other devices to simulate the mechanical stress the tablets are exposed to during transpassage of the gastrointestinal tract. The obtained results showed that the drug release rates from PREGEFLO® PI10 matrix were not impacted by all the conditions studied. Therefore, the explored starch excipient offers an interesting potential as matrix former in controlled release tablets. Finally, to characterize the drug distribution throughout the matrix system, in particular in the “dry” and swollen tablet regions after hydration and the way the spatial distribution patterns change with time, the tablets were investigated using Raman imaging, SEM and Energy Dispersive X-ray Spectroscopy (EDX) before and after exposure to phosphate buffer. The Raman images confirmed that the drug is effectively trapped within the “dry” tablet core. The internal structure of the vacuum-dried tablets was visualized using SEM analysis. These observations highlighted the difference in the morphology between the “dry” core region and the region in which the tablet matrix underwent substantial swelling. The polysaccharide formed a continuous hydrogel in which the drug dissolved. SEM and EDX images have rendered visible the interface “dry “core-swollen gel and the spatial distribution of the drug in both regions. The diprophylline content is predictably much highe