Expert, Taft Health Centre, Shahid Sadoughi (Yazd) University of Medical Sciences and Health Services, Taft, Yazd, Iran.

Abstract

Introduction: Anal fissures are small tears in the lining skin of the anus presenting with typical symptoms of pain and bleeding during defecation. Several new forms of medicines such as glyceryle trinitrate (GTN) ointments and diltiazem, a calcium channel-blocking agent, have been recently used for the treatment of these fissures. Diltiazem relaxes the muscle of anal sphincter and consequently increases blood flow to promote healing. It does not have GTN side effects like headache, anal burning and hypotension. The objective of this study was to formulate a suitable topical gel from diltiazem and then to investigate its physicochemical stability and also the drug release profiles from the bases. Methods: Various formulations of gel base including Guar 1.25%, Tragacanth 1.5%, HPMC 1%, and HPMC 1.5% were prepared and in vitro release and penetration characteristics of diltiazem from each preparation were studied through a hydrophilic dora pore diffusion barrier and membrane excised rat skin using Franz cell over a period of 5 hours. The amount of drug released from topical preparations was determined spectrophotometrically at max=236 nm. Stability studies and shelf life assessments were performed too. Results: Gel formulations containing HPMC, Guar and Tragacanth presented both good chemical and physical stabilities. The rates of cumulative drug release from HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases using synthetic membrane were 89.7%, 76.7%, 94.9% and 66.1% respectively. For excised rat skin test, the cumulative percent of penetrated drug at the end of each experiment were 52.7 %, 50.9%, 64.6% and 42.6% for HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases respectively. Conclusion: The comparative study showed that the percent of drug release from synthetic membrane was more than the percent of penetrated drug through excised rat skin for all bases (P<0.05). It was concluded that the kinetics of diltiazem release in vitro was not affected by the kind of gel forming agent and for all of the formulations, Higuchi's kinetic model was suitable to explain their kinetics.