IN-VITRO AND IN-VIVO AVAILABILITY OF MEBEVERINE HYDROCHLORIDE SUPPOSITORIES

摘要

Mebeverine hydrochloride suppositories were prepared using Witepsol H15 suppository base. The effect of different concentrations of various enhancers (surfactants, amino acids and osmotic modifiers) on the drug release form the prepared suppositories was studied. The results showed that mebeverine hydrochloride suppositories containing Brij 35 (2%) and urea (10%) were superior to the other formulations containing the tested enhancers. These formulae showed the highest release rates (K = 0.083 ± 0.004 min~(-1) and 0.111 ± 0.005 min~(-1), respectively) that followed first-order kinetics with t_(50%) of 8.35 ± 0.45 min and 6.24 ± 0.33 min, respectively. Therefore, these two formulae with the control suppositories were subjected to in vivo study in albino rabbits compared to the commercial Duspatalin~® tablets and intravenous injection. Higher C_(max) (1770.26 ± 165.46 ng.ml~(-1)) within shorter T_(max) (0.75 ± 0.20 h) was observed after rectal administration of the control suppositories compared to that of commercially available film-coated tablets (Duspatalin~® - 135 mg). A significant difference (p ≤ 0.05) between the absolute bioavailability of Duspatalin~® tablets (27.09 ± 3.80%) and control suppositories (46.66 ± 1.72%) was detected. Statistically (p ≤ 0.05), the mean residence time (MRT) after oral administration of Duspatalin~® tablets (3.16 ± 0.30 h) was significantly longer than that after the rectal administration of control suppositories (2.73 ± 0.30 h). suppositories containing 2% Brij 35 showed higher plasma levels of the drug (2766.11 ± 339.50 ng.ml~(-1)) with an absolute bioavailability of 70.50 ± 10.51% compared to 27.09 ± 3.80% for Duspatalin~® tablets.