Losartan potassium sustained release pellets with improved in vitro and in vivo performance

The aim of this study was to formulate and evaluate SR matrix pellets containing losartan potassium (LP) solid dispersion using extrusion-spheronization technique to minimize the fluctuation of its plasma concentration. LP solid dispersions were prepared by using different hydrophobic polymers at different weight ratios (0.5, 1, 2, and 5%). LP-Eudragit RS solid dispersion at 1:5 ratio resulted in slower drug release (only 20% of LP was released in about 8 h). Different concentrations of hydrophilic polymer, PEG 6000, were mixed with Avicel^® PH 101 to prepare the LP SR matrix pellets containing solid dispersion using 3² full factorial design to evaluate the effects of formulation parameters on the pellets attributes. The magnitude of torque for the pellet wet masses and binder ratio were decreased significantly with increasing PEG 6000 concentration. LP sustained release pellet formula composed of 9.24% PEG 6000 and 8 × 10^-9% PVP K30 solution was chosen as optimized formula. Pharmacokinetic studies revealed that calculated t _max was 9.72 ± 2.22 h from the optimized sustained release pellets compared to 2.11 ± 0.49 h in case of Cozaar^® immediate release tablet, indicating a slower release of the LP from pellets.