New formulation of in situ gelling Metolose-based liquid suppository

Abstract

Context: An in situ gelling liquid suppository is liquid at room temperature but forms a gel at body temperature. In our work, Metolose® SM-4000 (methylcellulose) is studied that basically shows thermal gelation at 68°C (2%, w/w). Objective: The objective was to study the potency of different factors (concentration, pH, additives) to change the value of thermal gelation temperature (T _t) for Metolose® to form an in situ gelling liquid suppository. Materials and methods: We studied the effect of Metolose® concentration, pH, and salts (sodium chloride, potassium chloride, sodium hydrogen carbonate, and sodium monohydrogen phosphate) on T _t by viscosimetry. To choose the appropriate compound, in vitro drug release was examined. Rectal safety test was performed on rats in vivo after 12-hour application. Results: Increasing the Metolose® concentrations (0.5–4%, w/w), T _t can be decreased, but it also altered the consistency of gel. pH does not affect the T _t. The water-soluble salts allowed reducing the gelation temperature to 37°C. Sodium monohydrogen phosphate in 4.5% concentration was found to be the most appropriate. The impact of examined factors on in vitro drug release of piroxicam from the in situ-formed gel was characterized according to Fickian diffusion. Metolose® and the chosen salt did not cause any morphological damage on the rectal tissues. Discussion: According to our study, Metolose® has the physical and chemical potential to be used as base for liquid suppositories.

• In situ gelling suppository
• Metolose®
• piroxicam