Formulation, in-vitro release and ex-vivo spasmolytic effects of mebeverine hydrochloride suppositories containing polycarbophil or polysorbate 80

Abstract

The release of mebeverine hydrochloride, in two different strengths 100 and 200 mg, from different suppository bases was studied in-vitro to choose the best base to be used in-vivo. The results showed that the fastest release of the drug was from polyethylene glycol 4000 suppository base. On studying the effects of the suppositories on some spasmogens on the isolated guinea-pig ileum the polyethylene glycol suppository containing 100 mg drug gave zero antagonism to acetyl choline (ACh), histamine and barium chloride (BaC1 2). Addition of 1% Tween 80 or 5% polycarbophil to the suppository formulation resulted in 33.3, 29.5, 12.1 and 25.3, 32.7 and 25.7% antagonism to ACh, histamine and BaC1 2, respectively. The suppository formulation containing 200 mg drug produced 60, 33.3 and 60% antagonism to the three agonists arranged in the same order previously mentioned. The addition of 1% Tween 80 or 5% polycarbophil to the formulation resulted in a significant increase in the drug antagonism to the three agonists producing 86, 65, 62 and 90, 66 and 90% antagonism, respectively. Weighing the suppository remaining after 2 h of administration revealed that addition of 1% Tween 80 to the formulation increased significantly ( P < 0.05) the dissolution of the suppository by 52–58% indicating the wetting effect of that additive. While, addition of 5% polycarbophil although improved the availability of the drug it did not affect the dissolution of the suppository indicating the adhesive effect that the polycarbophil exerts between the particles.