Siepmann F, Le Brun V, Siepmann J
College of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169 Berlin, Germany.
J Control Release. 2006 Oct 27;115(3):298-306. doi: 10.1016/j.jconrel.2006.08.016. Epub 2006 Sep 1.
The objective of the present study was to investigate and quantify the effects of ibuprofen, chlorpheniramine maleate and metoprolol tartrate on the thermal, mechanical and diffusional properties of polyacrylate-based films. Thin drug-containing films were prepared from organic Eudragit RS solutions and physicochemically characterized with respect to their glass transition temperature, mechanical properties and drug release kinetics in phosphate buffer pH 7.4. The apparent diffusion coefficient of the drug within the polymeric systems was determined by fitting an adequate solution of Fick's second law of diffusion to the experimentally determined release profiles. Importantly, the glass transition temperature of the films significantly decreased with increasing initial drug content, whereas the film flexibility and drug release rate increased. This clearly indicates that the three drugs act as efficient plasticizers for Eudragit RS. Interestingly, the mathematical analysis revealed that drug release was primarily controlled by diffusion. An increase in the initial drug content resulted in increased drug diffusivities and, thus, accelerated (absolute and relative) drug release rates. Importantly, quantitative relationships could be established between the drug diffusivity and the initial drug content. Based on this knowledge, the effects of the films' composition and thickness on the resulting drug release kinetics (also from coated solid dosage forms) can be predicted in a quantitative way.
本研究的目的是研究并量化布洛芬、马来酸氯苯那敏和酒石酸美托洛尔对聚丙烯酸酯基薄膜的热性能、力学性能和扩散性能的影响。由有机丙烯酸树脂溶液制备含药薄膜，并对其玻璃化转变温度、力学性能以及在pH 7.4磷酸盐缓冲液中的药物释放动力学进行了物理化学表征。通过将菲克第二扩散定律的适当解拟合到实验测定的释放曲线来确定药物在聚合物体系中的表观扩散系数。重要的是，薄膜的玻璃化转变温度随着初始药物含量的增加而显著降低，而薄膜柔韧性和药物释放速率增加。这清楚地表明这三种药物对丙烯酸树脂起有效的增塑剂作用。有趣的是，数学分析表明药物释放主要受扩散控制。初始药物含量的增加导致药物扩散系数增加，从而加速（绝对和相对）药物释放速率。重要的是，可以在药物扩散系数和初始药物含量之间建立定量关系。基于这一认识，可以定量预测薄膜组成和厚度对最终药物释放动力学（也包括包衣固体剂型）的影响。
