Samani Soliman Mohammadi, Montaseri Hashem, Kazemi Abdolghani
Department of Pharmaceutics, Shiraz University of Medical Sciences, Shiraz, Iran.
Eur J Pharm Biopharm. 2003 May;55(3):351-5. doi: 10.1016/s0939-6411(03)00030-4.
The purpose of this study was to evaluate the effect of polymer blends on the in vitro release profile of diclofenac sodium. Several controlled release matrices of diclofenac sodium with different proportions of hydroxypropyl methylcellulose (HPMC; viscosity grade 60 and 500 mPa.s), carbopol 940 and lactose as a water soluble filler were prepared. The results showed that when HPMC (viscosity grade 60 mPa.s) alone was used as matrix former, diclofenac sodium was released fast but the release rate became slower with HPMC (viscosity grade 500 mPa.s) at higher polymer/drug ratios (more than 0.8:1). However in lower polymer/drug ratios (lower than 0.7:1) the release rate still was fast. The results showed that carbopol can extend the release time appreciably but the release profiles had considerable fluctuations, and drug release in first hours was slow but increased appreciably with time at the end of profiles. When an appropriate blend of HPMC (viscosity grade 60 or 500 mPa.s) and carbopol 940 was used, the drug release became more uniform and its kinetic approached to zero order and release fluctuations were diminished. The results with these polymer blends showed that it is possible to reduce the total amounts of polymer in each formulation. According to kinetic analysis data, drug release from these matrix tablets did not follow Fick's law of diffusion and the results were in agreement with the earlier reports.
本研究的目的是评估聚合物共混物对双氯芬酸钠体外释放曲线的影响。制备了几种不同比例的羟丙基甲基纤维素(HPMC;粘度等级为60和500 mPa·s)、卡波姆940和乳糖作为水溶性填充剂的双氯芬酸钠控释基质。结果表明,当单独使用HPMC(粘度等级为60 mPa·s)作为基质形成剂时,双氯芬酸钠释放迅速,但在聚合物/药物比例较高(大于0.8:1)时,使用HPMC(粘度等级为500 mPa·s)时释放速率变慢。然而,在较低的聚合物/药物比例(低于0.7:1)下,释放速率仍然很快。结果表明,卡波姆可以显著延长释放时间,但释放曲线有相当大的波动,最初几小时药物释放缓慢,但在曲线末端随着时间推移显著增加。当使用HPMC(粘度等级为60或500 mPa·s)和卡波姆940的适当共混物时,药物释放变得更加均匀,其动力学接近零级,释放波动减小。这些聚合物共混物的结果表明,可以减少每种制剂中聚合物的总量。根据动力学分析数据,这些基质片剂的药物释放不遵循菲克扩散定律,结果与早期报告一致。