In vivo assessment, formulation, characterization and enhancing pharmacotherapy of encapsulated mini tablets for immediate release Sildenafil citrate and sustained release Bosentan

Abstract

The purpose of this study was to prepare and evaluate multiple unit mini tablets (MTs) of prolonged released (PR) bosentan (BSN) and fast release (FR) sildenafil citrate (SDC) on the basis of encapsulation method for the effective management of pulmonary artery hypertension. The system consists of MTs are in the form of uncoated tablets containing the superdisintegrating agents where as the PRMTs contains the polymer with film coating. All the units are prepared by direct compression method and encapsulated using size 1 hard gelatin capsule shells. The formulations were evaluated for differential scanning calorimetry, dissolution test and post compression studies for their quality attributes and it was found that all the parameters were in the acceptable limits. The optimized formulation for BSN PRMTs i.e BS3 which contains 5 % HPMC K15M shows a promising sustained release profile of 82.31 % in 24 h similarly FRMTs of SDC of formulation SD6 that having 3 % of magnesium aluminium silicate shows about 90 % of drug release within 15 min. The in-vivo pharmacokinetic characterization of the system was carried out using wister rats where the AUC value for SDC FRMTs and BSN PRMTs was found to be 94256.88625 ± 123.65 ng h/mL and 142438.084 ± 324.11 ng h/mL respectively. The other pharmacokinetics are also determined and found to be satisfactory. The six months stability samples showed no significant change in the drug content, hardness and uniformity of the content of the optimized formulations.