Effect of supersaturation and crystallization phenomena on the release properties of a controlled release device based on EVA copolymer

被引:49
作者
van Laarhoven, JAH
Kruft, MAB
Vromans, H
机构
[1] NV Organon, Dept Pharmaceut, NL-5340 BH Oss, Netherlands
[2] Univ Utrecht, Fac Pharm, Dept Pharmaceut, NL-3508 TB Utrecht, Netherlands
关键词
drug delivery; controlled release; supersaturation; solubility; crystallization; polyethylene vinylacetate;
D O I
10.1016/S0168-3659(02)00139-6
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
This study describes the influence of steroid concentration, manufacturing and storage on the release properties of etonogestrel from polyethylene vinylacetate (EVA) based coaxial fibers. Coaxial fibers were manufactured by extrusion technology. As a consequence of the high extrusion temperatures large amounts of etonogestrel dissolve in the polymeric melt. Since the release from the coaxial fibers is directly proportional to the concentration gradient over the membrane, the amount of dissolved drug that recrystallizes upon cooling is of crucial importance. Therefore crystallization kinetics were studied using thermal analysis and hot stage microscopy. It was found that if the amount of etonogestrel is below a critical nucleation concentration at room temperature, the dissolved steroid remains in a supersaturated state. If on the other hand the amount of dissolved steroid is just above the critical nucleation concentration, the supersaturated steroid recrystallizes very slowly. It is concluded that the release of etonogestrel from an extruded coaxial fiber is a result of a complicated set of parameters, where, respectively process conditions, concentration of etonogestrel and both time and temperature of storage are of importance. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:309 / 317
页数:9
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