Formulation and in vitro evaluation of verapamil HCl suppositories

Abstract

19 formulations of verapamil HCl in different water-soluble and fatty bases were prepared. Fatty bases included Witepsol H15, Witepsol E75. Suppocire AM and their mixtures. PEGs of different molecular weights and mixtures thereof represented the water-soluble bases. Urea and lysine HCl were included as additives in some formulations to investigate their role in enhancement of drug release and diffusion through the membrane barrier. All the formulations proved to be satisfactory as regards content uniformity and other physical tests: appearance, melting range, breaking test and disintegration. Release experiments from the different suppository bases, with or without the use of membrane barriers, were conducted using the USP XXII dissolution tester. Cellophane bags containing 10 ml of the dissolution medium were used to represent the rectal compartment. The data obtained from these experiments proved the superiority of the PEG formulation (PEG 1500: PEG 6000: water: 05:28:7): T 90%, 180 min using the bag. However, it appears that increasing the proportion of high molecular weight fraction of PEG in the formulation has an adverse effect on the rate and extent of diffusion of the drug through the membrane. Good results were also obtained with the mixtures of Witepsol E75:Witepsol H15 (1:3) and Witepsol E75:Suppocire AM (1:1); T 70%, 120 and 210 min, respectively, using the bag. Lysine HCl and urea improved the release of the drug from Witepsol-E75 probably by decreasing the melting point and increasing the spreading coefficient of the base. An optimum concentration of each additive was found to exert the desired enhancement of release.