Wu Baojian, Chen Zhukang, Wei Xiuli, Sun Ningyun, Lu Yi, Wu Wei
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, PR China.
Eur J Pharm Biopharm. 2007 Nov;67(3):707-14. doi: 10.1016/j.ejpb.2007.04.016. Epub 2007 Apr 30.
Calcium-induced crosslinking of pectin acts as the dominating factor controlling drug release from pectin-based matrices. The same interaction was employed to modify indomethacin release from HPMC/pectin/calcium matrix in this study. The aim was to characterize the release profiles, and to study the formulation variables and the underlying mechanisms. The matrix tablet was made up of pectin HM 70, calcium chloride and HPMC K4M, and prepared by the wet granulation method. In vitro release was performed in water and characterized by the power law. Matrix erosion was evaluated by studying the weight loss and pectin release. Biphasic release of indomethacin from the HPMC/pectin/calcium matrix tablet was observed, and extraordinary power law exponent n values of over 1.0 were observed. Increase in calcium amount led to more significant retardation on drug release. The two power law parameters, n and K, correlated to the amount of calcium in the matrix. A lag time of over 4 h can be achieved at HPMC/pectin/calcium chloride amount of 100 mg/100 mg/100 mg. Both matrix weight loss and pectin release were linearly correlated to indomethacin release, indicating erosion-controlled drug release mechanisms. The hybrid matrix showed retarded erosion and hydration rate, which served as the basis for retarded indomethacin release. It is concluded that the pectin/calcium interaction can be employed to modify drug release from HPMC/pectin/calcium matrix tablet with biphasic release patterns for potential timed or site-specific drug delivery.
钙诱导的果胶交联是控制药物从果胶基基质中释放的主要因素。本研究采用相同的相互作用来改变吲哚美辛从羟丙甲纤维素/果胶/钙基质中的释放。目的是表征释放曲线，研究配方变量和潜在机制。基质片剂由果胶HM 70、氯化钙和羟丙甲纤维素K4M组成，采用湿法制粒法制备。在水中进行体外释放，并以幂律进行表征。通过研究失重和果胶释放来评估基质侵蚀。观察到吲哚美辛从羟丙甲纤维素/果胶/钙基质片剂中的双相释放，并且观察到异常的幂律指数n值超过1.0。钙含量的增加导致药物释放的延迟更显著。两个幂律参数n和K与基质中钙的含量相关。在羟丙甲纤维素/果胶/氯化钙含量为100 mg/100 mg/100 mg时可实现超过4小时的滞后时间。基质失重和果胶释放均与吲哚美辛释放呈线性相关，表明药物释放机制受侵蚀控制。混合基质显示出延迟的侵蚀和水合速率，这是吲哚美辛释放延迟的基础。结论是，果胶/钙相互作用可用于改变羟丙甲纤维素/果胶/钙基质片剂的药物释放，具有双相释放模式，用于潜在的定时或定点给药。
