Rege Pankaj R, Shukla Dhruti J, Block Lawrence H
Department of Medicinal Chemistry and Pharmaceutics, Duquesne University, Pittsburgh, PA 15282, USA.
Int J Pharm. 2003 Jan 2;250(1):259-72. doi: 10.1016/s0378-5173(02)00551-3.
The purpose of this study was to examine the potential use of electrolytes to control naproxen sodium (I) release from chitinosan (II) tablets. An ANOVA was employed to evaluate the effects of molecular weight (MW) of II, electrolyte valence (EV), and pH of the dissolution medium on I's release. The intrinsic dissolution rates and saturation solubilities of I were determined at each of the pHs used. Directly compressed tablets were prepared from admixtures containing: I, NaCl, CaCl(2), or AlCl(3), Mg stearate, and II. The tablets were characterized for their dimensions, crushing strengths, friability, disintegration times, and in vitro dissolution profiles. The slopes of the log-log cumulative percent released-time curves (t=0-5 h) were compared using ANOVA. Based on the ANOVA, each of the variables-chitinosans, EVs, and pHs-significantly affected drug release (P<0.05). Besides the poor aqueous solubility of I, the factors possibly affecting drug release included: (a) the formation of a rate-limiting II gel barrier; (b) the interaction of I with ionized amino groups of II; (c) the effect of electrolyte on the II's gel barrier formation; and/or (d) decreased aqueous solubility of I in the presence of electrolyte.
本研究的目的是考察电解质在控制萘普生钠（I）从壳聚糖（II）片剂中释放方面的潜在应用。采用方差分析来评估II的分子量（MW）、电解质价态（EV）以及溶出介质的pH对I释放的影响。在每个使用的pH条件下测定I的固有溶出速率和饱和溶解度。由含有I、氯化钠、氯化钙、氯化铝、硬脂酸镁和II的混合物直接压片制备片剂。对片剂的尺寸、抗压强度、脆碎度、崩解时间和体外溶出曲线进行表征。使用方差分析比较对数-对数累积释放百分比-时间曲线（t = 0 - 5小时）的斜率。基于方差分析，每个变量——壳聚糖、EV和pH——均显著影响药物释放（P < 0.05）。除了I的水溶性较差外，可能影响药物释放的因素包括：（a）形成限速的II凝胶屏障；（b）I与II的离子化氨基的相互作用；（c）电解质对II凝胶屏障形成的影响；和/或（d）在电解质存在下I的水溶性降低。
