Reza Md Selim, Quadir Mohiuddin Abdul, Haider Syed Shabbir
Department of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh.
Pak J Pharm Sci. 2002 Jan;15(1):63-70.
Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.
本研究开发了由科利通SR（基于聚醋酸乙烯酯和聚维酮的缓释聚合物）构成的茶碱缓释骨架片，旨在设计一种具有理想释放曲线且完全符合官方药典的剂型。通过将科利通SR和羟丙基甲基纤维素-15cps（羟丙基甲基纤维素）按不同比例与固定百分比的茶碱进行干混和直接压片，制备了四种骨架片制剂。仅含科利通SR和活性成分的片剂显示出快速的药物释放速率，并伴有初始突释效应。如平均溶出时间、T50和 Higuchi释放速率数据所证实，在骨架片中加入羟丙基甲基纤维素-15cps可延长药物释放时间，并随后使突释效应最小化。在含羟丙基甲基纤维素-15cps的批次中，释放速率与所用羟丙基甲基纤维素的百分比之间存在直接关系。含有20%科利通SR和30%羟丙基甲基纤维素-15cps的骨架片获得了合适的控释曲线。该制剂与市售产品非常相似，并符合美国药典规范。通过聚合物的物理化学性质和水化特性的差异对结果进行了探讨和解释。除此之外，还应用指数模型来表征药物从聚合物体系中的释放行为。结果发现，仅含科利通SR的片剂中以菲克扩散释放为主，而在含羟丙基甲基纤维素的片剂中，非菲克扩散机制在药物释放中起重要作用，且有趋向零级或Ⅱ型释放的趋势。还对两个商业品牌的体外释放曲线进行了测定，以比较和调整实验批次。
