Stability and permeability studies of Cimetidine gel formulations

Cimetidine is approved by the FDA for inhibition of gastric acid secretion, however several studies have shown that cimetidine may be effective also for a number of dermatological diseases. The cutaneous immunological effects of Cimetidine have been actively studied since the introduction of cimetidine on the market 30 years ago. However, to the best of out knowledge, the shelf life and the penetration properties of Cimetidine topical preparations is still unknown. Specifically, the purpose of this study was: (1) to determine the stability of Cimetidine in three different gel formulations (Carbopol RTM 973-P-NF, UltrezRTM 20 and Klucel(TM)) and three different solvent systems (A, B, and C) at room temperature. (2) to assess the permeability of the selected gel formulations through cellulose membrane. (3) to assess the effect of penetration enhancers like oleic acid (0.4% 1%, 5%) and menthol (1%, 2.5%, 5%) on selected gel.;Cimetidine 0.5% gel formulations were stored at room temperature (25 +/- 1°C) over a period of 28 days. Gel samples were collected every week and analyzed for cimetidine content by a validated HPLC method. Cimetidine was stable only in solvent system A (Propylene Glycol: Ethanol: Water: 5:4:1) out of solvent system A (Propylene Glycol: Ethanol: Water: 5:4:1), solvent system B (Propylene Glycol: Ethanol: Water: 6:3:1) and solvent system C (Propylene Glycol: Ethanol: Water: 7:2:1). The Cimetidine gel formulation in carbopol gel was stable for 7 days, in ultrez gel for 15 days and in klucel gel, it was stable for less than one week. Therefore, the gels in carbopol and ultrez in solvent system A were selected as base gel to investigate the effect of three levels of the penetration enhancers menthol and oleic acid.