Drug release behaviour from methyl methacrylate-starch matrix tablets: effect of polymer moisture content.
The aim of this work was to study the effect of the initial moisture content of the polymer on the tabletting and drug release behaviour of controlled release inert matrices elaborated with methyl methacrylate (MMA)-starch copolymers. The copolymers, obtained by free radical polymerisation and dried by two different methods (oven-drying or freeze-drying), were equilibrated at different relative humidities (0%, 25%, 50% and 75% RH) at room temperature. From these copolymers, matrix systems were directly compressed containing either a slightly water-soluble drug (anhydrous theophylline) or a freely water-soluble drug (salbutamol sulphate), and their compaction properties and in vitro dissolution profiles were evaluated. The release profiles were compared following model-independent methods, such as the Qt parameter and the similarity factor f2. Moreover, several kinetic models were employed to evaluate the possible changes in the release mechanism. For anhydrous theophylline, the initial moisture content of the copolymers did not affect the release characteristics from the inert matrices under study, and a typical Fickian diffusion mechanism was observed for the different formulations. However, in case of salbutamol sulphate, the presence of moisture might induce a fast drug dissolution, promoting the weakness of the matrix structure and hence, its partial disintegration. So, an "anomalous" mixed phenomenon of diffusion and erosion was found, influenced by the initial moisture content of the copolymer.
Bravo-Osuna
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Dpto. Farmacia y Tecnología Farmacéutica, Universidad de Sevilla, Sevilla, Spain.
Ferrero
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Jiménez-Castellanos
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D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D020366:Methylmethacrylate / Q000737:chemistry*; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013213:Starch / Q000737:chemistry*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
D004364:Pharmaceutical Preparations; D011108:Polymers; D013607:Tablets; D014867:Water; D020366:Methylmethacrylate; D013213:Starch