Development and in vitro–in vivo relationship of controlled-release microparticles loaded with tramadol hydrochloride

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., Cmax, tmax, AUC0–∞ 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 Tmax, t1/2 and MRT, and higher values of Cmax and Ke were observed for F-3. The control formulation (immediate-release) presented lowest values of t1/2, MRT and Tmax but the highest values of Cmax and Ke. 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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide