This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

译文

:这项工作涉及通过熔融制粒和随后的压制制备的缓释微型片剂(MT)的开发和体外评估,这些制剂旨在长时间漂浮。左旋多巴用作模型药物。然后检查了MT的组成和制造参数对它们的漂浮和溶解特性的重要性。调查表明,MT的组成和MT的直径对药物释放的影响最大,持续时间超过8h。通过使用相同的配方,在50至100N的低压缩力下制备3mm MT可获得最佳漂浮性能。它们的总重量(RW)值始终高于在13小时内使用市售HBS剂型获得的结果。当将它们装入明胶胶囊中时,未观察到粘附。通过评估左旋多巴在不同pH值下的溶出曲线,发现溶出曲线更多地取决于Methocel K15M的延长释放能力,而不是取决于左旋多巴的pH依赖性溶解度。最后,通过在溶出度测试中测试药物释放在搅拌条件下的功能变化来评估浮动MT的坚固性。

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