Kim H, Fassihi R
Temple University, School of Pharmacy, Philadelphia, PA 19140, USA.
J Pharm Sci. 1997 Mar;86(3):316-22. doi: 10.1021/js960302s.
A new binary polymer matrix tablet for oral administration was developed. The system will deliver drug at variable rates according to zero-order kinetics for total drug content and is manufactured by direct compression technology. Highly methoxylated pectin and hydroxypropyl methylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results indicate that by increasing pectin:HPMC ratios, release rates are increased, but zero-order kinetics prevail throughout the dissolution period (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of viscosities that modulates drug release and results in rapid hydration/gelation in both axial and radial directions, as evidenced by photomicrographic pictures. This hydration-gelation contributes to the development of swelling/erosion boundaries and consequently to constant drug release. Combination of these particular polymers facilitates rapid formation of necessary boundaries (i.e., gel layer and solid core boundaries) to control overall mass transfer processes. The drug fraction released (Mt/M infinity), release kinetics, and mechanism of release were analyzed by applying the simple power law expression Mt/M infinity = kt(n), where k is a kinetic constant and the exponent n is indicative of the release mechanism. The calculated n values for pectin:HPMC ratios of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II transport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulated by the gelling characteristics of polymers in the formulation.
开发了一种新型口服二元聚合物基质片剂。该系统将根据总药物含量的零级动力学以可变速率释放药物，并采用直接压片技术制造。使用不同比例的高甲氧基果胶和羟丙基甲基纤维素（HPMC）作为主要配方成分，并将泼尼松龙用作药物模型。结果表明，通过增加果胶与HPMC的比例，释放速率会提高，但在整个溶解期（例如3 - 22小时）内零级动力学占主导。不同的果胶与HPMC比例提供了一系列粘度，可调节药物释放，并导致在轴向和径向上快速水合/凝胶化，显微照片证明了这一点。这种水合 - 凝胶化有助于形成溶胀/侵蚀边界，从而实现药物的持续释放。这些特定聚合物的组合有助于快速形成必要的边界（即凝胶层和固体核心边界），以控制整体传质过程。通过应用简单的幂律表达式Mt/M∞ = kt(n)分析释放的药物分数（Mt/M∞）、释放动力学和释放机制，其中k是动力学常数，指数n表示释放机制。果胶与HPMC比例为4:5、3:6和2:7时计算得到的n值>0.95，这表明是II型转运机制（聚合物松弛/溶解）。实现完全零级动力学是由于可预测的溶胀/侵蚀以及最终聚合物链的解聚和溶解，这由配方中聚合物的胶凝特性调节。
