Formulation and Evaluation of Diltiazem Hydrochloride Gels for the Treatment of Anal Fissures

The treatment for chronic anal fissure (CAF) has undergone a transformation in recent years from surgical to medical. Both the approaches share the common goal of reducing the spasm of anal sphincter. Though surgical treatment has a high success rate but it can permanently impair fecal continence in large number of patients. Smooth muscle relaxation seems to be a novel way by which more than 60% of the patients can be cured with the topical use of the agents. In the present investigation, diltiazem hydrochloride gels were prepared using FDA recommended polymers [hydroxypropylmethyl cellulose (HPMC), methylcellulose (MC) and polyethylene oxide (PEO grade 301 and 303)] for topical application in CAF. Increasing the concentration of the polymer significantly increased the consistency of the gels. All the formulations exhibited pseudoplastic flow with no thixotropy. The values of flow index (n) were found to be less than one for all the gels confirming the shear thinning behaviour of all the gels. HPMC and MC gels were found to be stable at accelerated stability conditions while the bioadhesion of PEO gels was highest. Even after exposure to heat and humidity, no significant change was observed in the content uniformity, pH, clarity, texture profile analysis and rheological properties of the HPMC and MC gels. The rheograms and various power law equation parameters of these gels were found comparable at various time points in the accelerated stability study. However, PEO gels failed in accelerated stability studies at one month sample. When four selected gel formulations (HPMCL4, MCL3, P1BL3 and P3BL3.5) were applied topically by six patients each, Gastrointestinal Quality of Life Index (GIQLI) score of each patient was improved at the end of 8 weeks. No adverse effects were reported by any of the patients. Hence 2% DTZ gel was found to be effective in the treatment of anal fissures.