Apicella A, Cappello B, Del Nobile M A, La Rotonda M I, Mensitieri G, Nicolais L
Department of Materials and Production Engineering, University of Naples Federico II, Italy.
Biomaterials. 1993;14(2):83-90. doi: 10.1016/0142-9612(93)90215-n.
An interpretation of the drug release from monolithic water-swellable and soluble polymer tablets is presented. A convenient parameter, alpha, which compares the drug-diffusive conductance in the gel layer with the swelling and dissolving characteristics of the unpenetrated polymer was used to describe the release behaviour of beta-hydroxyethyl-theophylline (etofylline) from compression-moulded tablets of hydrophilic pure semicrystalline poly(ethylene oxides) of mol wt 600,000 and 4,000,000 and of two blends of the two molecular weights of poly(ethylene oxides). The water swelling and dissolution characteristics of two polymers and two blends were analysed, monitoring the thickness increase of the surface-dissolving layer and the rates of water swelling and penetration in the tablets. The drug diffusivities in the water-penetrated polymer gels were measured by carrying out permeation tests. Finally, drug release tests were performed to investigate the release kinetics of the different systems in an aqueous environment at 37 degrees C. The drug release from the high molecular weight poly(ethylene oxide) is principally related to the material swelling rather than polymer dissolution, leading to a progressive decrease of the drug's diffusive conductance in the growing swollen layer, and hence to a non-constant release induced by the prevailing diffusive control. Conversely, drug release from the low molecular weight poly(ethylene oxide) is strictly related to the polymer dissolution mechanism. The achievement of stationary conditions, in which the rate of swelling equals the rate of dissolution, ensures a constant release rate, even in the case of very low drug-diffusive conductance in the external gel layer. Intermediate behaviours were detected in the case of the two blends.
本文对整体式水溶胀和可溶聚合物片剂的药物释放进行了解释。使用了一个方便的参数α，它将凝胶层中的药物扩散传导率与未渗透聚合物的溶胀和溶解特性进行比较，以描述β-羟乙基茶碱（羟乙茶碱）从分子量为600,000和4,000,000的亲水性纯半结晶聚环氧乙烷以及两种分子量聚环氧乙烷的两种共混物的模压片剂中的释放行为。分析了两种聚合物和两种共混物的水溶胀和溶解特性，监测了表面溶解层的厚度增加以及片剂中的水溶胀和渗透速率。通过进行渗透试验测量了水渗透聚合物凝胶中的药物扩散系数。最后，进行了药物释放试验，以研究不同体系在37℃水性环境中的释放动力学。高分子量聚环氧乙烷的药物释放主要与材料溶胀有关，而不是聚合物溶解，导致药物在不断增长的溶胀层中的扩散传导率逐渐降低，从而导致主要由扩散控制引起的非恒定释放。相反，低分子量聚环氧乙烷的药物释放与聚合物溶解机制密切相关。达到溶胀速率等于溶解速率的稳态条件可确保恒定的释放速率，即使在外部凝胶层中药物扩散传导率非常低的情况下也是如此。在两种共混物的情况下检测到了中间行为。
