Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan.
Int J Pharm. 2011 Apr 4;407(1-2):38-43. doi: 10.1016/j.ijpharm.2011.01.005. Epub 2011 Jan 15.
In conclusion, the controlled-release microparticles of TmH can be developed via phase separation method. The development and optimization of controlled-release microparticles of tramadol hydrochloride (TmH) for the oral delivery and their in vitro and in vivo correlation was prime objective of the present study. Four formulations of controlled-released microparticles were developed and optimized in terms of encapsulation efficiency, dissolution study and release kinetics. Among all formulated microparticles F-3 (ratio of TmH:EC 1:2) and F-4 (ratio of TmH:EC 1:3) presented the better characteristics in reference to entrapment efficiency, release kinetics and dissolution profile compared to other formulations (F-1, F-2). For in vivo analysis a new HPLC analytical method was developed and validated. The optimized formulations were subjected to in vivo studies to calculate various pharmacokinetic parameters, i.e., C(max), t(max), AUC(0-∞) and MRT. The in vitro dissolution and in vivo absorption data was correlated with the help of Wagner-Nelson method. F-3 showed a good in vitro-in vivo correlation with a correlation determination of 0.9957. Moreover, lower T(max), t(1/2) and MRT, and higher values of C(max) and K(e) were observed for F-3. The control formulation (immediate-release) presented lowest values of t(1/2), MRT and T(max) but the highest values of C(max) and K(e). The controlled-release microparticles (F-3 and F-4) could sustain the drug release within therapeutic level up to 24 h and good IVIVC is expected from them.
总之，可以通过相分离法开发 TmH 的控释微球。本研究的主要目的是开发和优化盐酸曲马多（TmH）的控释微球用于口服给药及其体外与体内相关性。根据包封效率、溶出研究和释放动力学，开发和优化了四种控释微球制剂。与其他制剂（F-1、F-2）相比，所有配方的微球 F-3（TmH：EC 比 1:2）和 F-4（TmH：EC 比 1:3）在包封效率、释放动力学和溶解特性方面表现出更好的特性。为了进行体内分析，开发并验证了一种新的 HPLC 分析方法。将优化的制剂进行体内研究，以计算各种药代动力学参数，即 C(max)、t(max)、AUC(0-∞)和 MRT。借助 Wagner-Nelson 法对体外溶出度和体内吸收数据进行了相关性分析。F-3 显示出良好的体外-体内相关性，相关系数为 0.9957。此外，F-3 还表现出较低的 T(max)、t(1/2)和 MRT，以及较高的 C(max)和 K(e)值。对照制剂（速释）表现出最低的 t(1/2)、MRT 和 T(max)，但最高的 C(max)和 K(e)。控释微球（F-3 和 F-4）可将药物释放维持在治疗水平长达 24 小时，并有望具有良好的 IVIVC。
