Factors influencing the diffusion-controlled release of papaverine from poly (L-lactic acid) matrix
Factors influencing the diffusion-controlled release of papaverine from poly (L-lactic acid) matrix
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DOI：
10.1016/s0168-3659(98)00076-5
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发表时间：
1998-12-04
影响因子：
10.8
通讯作者：
Ikeda, M
中科院分区：
文献类型：
--
作者：
Miyajima, M;Koshika, A;Ikeda, M
考察了药物含量和介质pH对可生物降解的聚(L-乳酸)[P(L)LA]骨架中罂粟碱释放的影响，揭示了影响两阶段扩散控释机制的主要因素。采用热压法制备了药物溶解圆柱形骨架(棒状，直径10 mm×1 mm)。在PAP含量小于10%的情况下，pH对释放速率有很大的影响，药物含量对释放曲线没有影响。释放曲线由两个连续的扩散阶段组成，这是由于P(L)LA在释放前由非晶态转变为半晶态。在第一释放阶段，PAP在膨胀的基质中扩散。由于酸性P(L)LA棒材中水分含量的增加，释放速率随介质pH的升高而加快。在第二释放阶段，PAP通过聚合物结晶形成的充满水的微孔扩散。在假设药物在微孔中的聚合物和介质之间的分配影响扩散，并且分配受pH控制的情况下，我们推导了修正的扩散动力学方程。随着介质pH的增加，药物释放减速的现象可以用导出的方程来解释，这是由于药物对聚合物的分配增加所致。在棒状物含有超过15%的PAP的情况下，药物在释放过程中以结晶的形式析出。因此，这些棒状物表现出较慢的释放。(C)1998 Elsevier Science B.V.保留所有权利。
Effects of drug content and medium pH on the release of papaverine (PAP) from biodegradable poly(L-lactic acid) [P(L)LA] matrix were investigated to reveal the predominant factors affecting the two-stage diffusion-controlled release mechanism. A drug-dissolved cylindrical matrix (rod; 10 mm X 1 mm diameter) was prepared by heat compression method. In the case of a PAP content below 10%, pH was found to have a strong effect on the release rate, and drug content was found to have no effect on the release profile. The release profile consisted of two sequential diffusion stages due to P(L)LA transformation from amorphous to the semicrystalline state prior to release. In the first release stage PAP diffused through the swollen matrix. The release accelerated with increasing medium pH due to an increase in water content in the acidic P(L)LA rod. In the second release stage PAP diffused through the water-filled micropores developed as a result of the polymer crystallization. On the assumption that the drug partition between the polymer and the medium in the micropores affects the diffusion and the partition is controlled by pH, we derived a modified diffusion kinetic equation. The observation that the release decelerated with increasing medium pH can be explained by the derived equation as resulting from the increase in the drug partition to the polymer. In the case where the rods contained more than 15% of PAP, the drug precipitated out as crystals during release. Accordingly, these rods showed a slower release. (C) 1998 Elsevier Science B.V. All rights reserved.