Varshosaz Jaleh, Faghihian Hossein, Rastgoo Kobra
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Drug Deliv. 2006 Jul-Aug;13(4):295-302. doi: 10.1080/10717540500459308.
In recent years, great attention has been paid to using solid dispersions to make sustained-release drugs. The objective of this study is to produce sustained-release systems of metoprolol tartrate using solid dispersion techniques and to evaluate their physicochemical characteristics. The solid dispersions were produced by melting and solvent methods, containing 7%, 15%, or 25% of the drug and different ratios of Eudragit RLPO and RSPO in ratios of 0:10, 3:7, 5:5, 7:3, and 10:0. Drug release profiles were determined by USP XXIII rotating paddle method in phosphate buffer solution (pH 6.8). XRD, DSC, IR, and microscopic observations were performed to evaluate the physical characteristics of solid dispersions. Results showed that the drug release from dispersions was at a slower rate than pure drug and physical mixtures. Moreover, the formulations containing greater ratios of Eudragit RSPO showed slower release rates and smaller DE8% but larger mean dissolution time than those containing greater ratios of Eudragit RLPO. Dispersions with particle size of less than 100 microm containing 7% of metoprolol and Eudragit RL:RS 5:5 (solvent method) and those with the ratio of 3:7 (melting method) had similar release pattern to Lopressor sustained-release tablets by zero-order and Higuchi kinetics, respectively.
近年来，利用固体分散体来制备缓释药物受到了极大关注。本研究的目的是采用固体分散技术制备酒石酸美托洛尔缓释系统，并评估其理化特性。通过熔融法和溶剂法制备固体分散体，其中药物含量分别为7%、15%或25%，且Eudragit RLPO和RSPO的比例分别为0:10、3:7、5:5、7:3和10:0。采用美国药典XXIII桨法在磷酸盐缓冲溶液（pH 6.8）中测定药物释放曲线。通过X射线衍射（XRD）、差示扫描量热法（DSC）、红外光谱（IR）和显微镜观察来评估固体分散体的物理特性。结果表明，分散体中药物的释放速率比纯药物和物理混合物慢。此外，与含较高比例Eudragit RLPO的制剂相比，含较高比例Eudragit RSPO的制剂释放速率较慢，DE8%较小，但平均溶解时间较长。含7%美托洛尔且Eudragit RL:RS为5:5（溶剂法）的粒径小于100微米的分散体以及比例为3:7（熔融法）的分散体，分别通过零级动力学和 Higuchi动力学显示出与倍他乐克缓释片相似的释放模式。
