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., 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.
Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan. mna19bwp@yahoo.com
Muhammad
M
Naeem Aamir
Mahmood
M
Ahmad
Naveed
N
Akhtar
Ghulam
G
Murtaza
Shujaat Ali
SA
Khan
Shahiq-uz-Zaman
Ali
A
Nokhodchi
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008297:Male; D008863:Microspheres; D012995:Solubility; D013997:Time Factors; D014147:Tramadol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D005079:Excipients; D014147:Tramadol; C013517:ethyl cellulose; D002482:Cellulose