Qin Ling-hao, Yu Hong
Department of Pharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Yao Xue Xue Bao. 2010 Dec;45(12):1559-64.
This paper is to study the inhibitory effect of water soluble polymers--methyl cellulose (MC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC-M), poloxamer (F68) and polyvidon (PVP) on osthole (OST) crystallization and investigate the impact of polymer concentration and viscosity on crystallization behavior. Also, UV spectrophotometry method was used to determine the drug concentration at different time point to draw the OST concentration-time curve. Results show that HPMC has the most significant inhibition effect on OST crystallization, and drug concentration level is 1.61 times higher than that in control solution within 8 h followed by PVP (1.54) and MC (1.45) respectively. The kinetics of OST recrystallization can be described using first-order reaction, and the crystallization rate constants obtained by analyzing the regression equation indicate that HPMC-60SH-4000 and HPMC-60SH-10000 can greatly influence OST crystal formation. The dissolution rate of drugs precipitated from water-soluble polymer solutions is faster compared with controls in pH 1.2 HCl and pH 6.8 phosphate buffers, which demonstrated that water-soluble polymers can not only change the behavior of drug crystallization but markedly improve the dissolution rate of water insoluble drugs.
本文旨在研究水溶性聚合物——甲基纤维素（MC）、羟丙基甲基纤维素（HPMC）、羟丙基纤维素（HPC-M）、泊洛沙姆（F68）和聚维酮（PVP）对蛇床子素（OST）结晶的抑制作用，并考察聚合物浓度和黏度对结晶行为的影响。此外，采用紫外分光光度法测定不同时间点的药物浓度，绘制OST浓度-时间曲线。结果表明，HPMC对OST结晶的抑制作用最为显著，8 h内药物浓度水平分别是对照溶液的1.61倍，其次是PVP（1.54）和MC（1.45）。OST重结晶动力学可用一级反应描述，通过分析回归方程得到的结晶速率常数表明，HPMC-60SH-4000和HPMC-60SH-10000对OST晶体形成有很大影响。在pH 1.2盐酸和pH 6.8磷酸盐缓冲液中，从水溶性聚合物溶液中析出的药物溶解速率比对照更快，这表明水溶性聚合物不仅能改变药物结晶行为，还能显著提高水不溶性药物的溶解速率。
