Xu X, Lee P I
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Pharm Res. 1993 Aug;10(8):1144-52. doi: 10.1023/a:1018960016756.
An erodible association polymer system based on blends of cellulose acetate phthalate (CAP) and Pluronic F127, a block copolymer of poly(ethylene oxide) and poly(propylene oxide), has been investigated for its applicability to rate-programmed drug delivery. The compatibility and thermal properties were characterized by DSC and FTIR. Results from the thermal analysis indicate that the blends are compatible above 50% CAP, as revealed by a single composition-dependent glass transition temperature (Tg). The existence of molecular association through intermolecular hydrogen bonding between the carboxylic acid and the ether oxygen groups is supported by the observation of an upward shift in the IR carbonyl stretching frequency at increasing Pluronic F127 concentrations. Using theophylline as a model drug, the in vitro polymer erosion and drug release characteristics of the present polymer system were evaluated at different buffer pH's on a rotating-disk apparatus. The results show that the rates of both polymer erosion and drug release increase with the Pluronic F127 concentration in the blend. Further, at pH 4, the polymer erosion is minimal and the theophylline release appears to be governed mainly by diffusion through the polymer matrix. In contrast, at pH 7.4, the theophylline release is controlled primarily by the polymer surface erosion. To demonstrate the unique approach to programmed drug release based on the concept of nonuniform initial drug distribution, pulsatile patterns of drug release have been achieved successfully from the present surface-erodible polymer system using a multilaminate sample design with alternating drug-loaded layers.(ABSTRACT TRUNCATED AT 250 WORDS)
基于邻苯二甲酸醋酸纤维素（CAP）与聚环氧乙烷和聚环氧丙烷的嵌段共聚物普朗尼克F127的共混物的可侵蚀缔合聚合物体系，已针对其在速率程序控制药物递送中的适用性进行了研究。通过差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）对其相容性和热性能进行了表征。热分析结果表明，如单一的与组成相关的玻璃化转变温度（Tg）所示，共混物在CAP含量高于50%时具有相容性。随着普朗尼克F127浓度增加，红外羰基伸缩频率向上移动，这一观察结果支持了通过羧酸与醚氧基团之间的分子间氢键形成分子缔合。以茶碱为模型药物，在旋转圆盘装置上于不同缓冲液pH值下评估了本聚合物体系的体外聚合物侵蚀和药物释放特性。结果表明，聚合物侵蚀速率和药物释放速率均随共混物中普朗尼克F127浓度的增加而增加。此外，在pH 4时，聚合物侵蚀最小，茶碱释放似乎主要受通过聚合物基质的扩散控制。相比之下，在pH 7.4时，茶碱释放主要受聚合物表面侵蚀控制。为证明基于非均匀初始药物分布概念的独特的程序控制药物释放方法，使用具有交替载药层的多层样品设计，已从本表面可侵蚀聚合物体系成功实现了药物释放的脉冲模式。（摘要截短于250字）
