Kim H, Fassihi R
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, Pennsylvania 19140, USA.
Pharm Res. 1997 Oct;14(10):1415-21. doi: 10.1023/a:1012124806316.
The purpose of this study was to develop a new ternary polymeric matrix system that is easy to manufacture and that delivers a highly soluble drug over long periods of time.
Pectin, hydroxypropylmethylcellulose (HPMC), and diltiazem HCl granulated with gelatin at optimized ratios were blended at different loading doses and directly compressed. Swelling behavior, dissolution profiles and the effect of hydrodynamic stress on release kinetics were evaluated.
Diltiazem release kinetics from the ternary polymeric system was dependent on the different swelling behavior of the polymers and varied with the drug loading dose and hydrodynamic conditions. Drug release followed either non-Fickian or Case II transport kinetics. The relative influence of diffusion and relaxational/dissolution effects on release profiles for different drug loadings was calculated by a nonlinear regression approach. Photographs taken during swelling show that the anisotropic nature of the gel structure, drug loading dose, swelling capacity of polymers used, and the design of delivery system all play important roles in controlling the drug release and dissolution/erosion processes.
Zero-order delivery of diltiazem HCl from a simple tablet matrix was achieved. The ternary polymeric system developed in this study is suitable for controlled release of highly soluble drugs. It offers a number of advantages over existing systems, including ease of manufacturing and of release modulation, as well as reproducibility of release profiles under well defined hydrodynamic conditions. Our delivery system has the potential to fully release its drug content in a controlled manner over a long time period and to dissolve completely.
本研究的目的是开发一种新型三元聚合物基质系统，该系统易于制造，并能长时间递送高溶性药物。
将按优化比例与明胶制粒的果胶、羟丙基甲基纤维素（HPMC）和盐酸地尔硫䓬以不同载药量混合并直接压片。评估了溶胀行为、溶出曲线以及流体动力学应力对释放动力学的影响。
三元聚合物系统中盐酸地尔硫䓬的释放动力学取决于聚合物不同的溶胀行为，并随药物载药量和流体动力学条件而变化。药物释放遵循非菲克扩散或第二类转运动力学。通过非线性回归方法计算了不同药物载药量下扩散和松弛/溶解效应对释放曲线的相对影响。溶胀过程中拍摄的照片表明，凝胶结构的各向异性性质、药物载药量、所用聚合物的溶胀能力以及给药系统的设计在控制药物释放和溶解/侵蚀过程中均起着重要作用。
实现了盐酸地尔硫䓬从简单片剂基质的零级释放。本研究开发的三元聚合物系统适用于高溶性药物的控释。与现有系统相比，它具有许多优点，包括易于制造和调节释放，以及在明确的流体动力学条件下释放曲线的可重复性。我们的给药系统有可能在很长一段时间内以可控方式完全释放其药物含量并完全溶解。
