Study on physical and chemical stability of different indomethacin semi-solid formulations

Abstract

Introduction: Indomethacin is a nonsteroidal anti-inflammatory drug used for the treatment of many inflammatory conditions. Formulation of indomethacin dosage forms and enhancement of drug bio­availability is quite challenging considering its poor solubility in water, as well as in oils, and its con­siderable chemical instability due to hydrolysis. The purpose of the study was to assess physical and chemical stability of different indomethacin semi-solid formulations eligible for mucosal application as a function of the semi-solid base used. Furthermore, based on the experimental data, to predict and optimize formulations stability during storage and shelf life. Materials and Methods: All experimental formulations were prepared with 1% indomethacin as ac­tive ingredient. Three types of gelling agents were used - Methylcellulose, Poloxamer 407 and Car­bomer 940 - for the preparation of hydrogels and emulgels. Experimental formulations were tested along with USP standard indomethacin 1% gel and marketed in Bulgaria as a combined paste with indomethacin - Indextol. Samples were stored and observed for physical stability at 4 0C and 25 0C for three months. Formulations that exhibited satisfactory physical stability were subjected to an ac­celerated chemical stability test at 100 0C in order to determine drug hydrolysis kinetics and predict product shelf life. Results: Tests reveal better physical stability of emulgels compared to corresponding hydrogels. Hy­drogel with Methylcellulose was found to form a sediment at both temperatures in a few weeks. Emul­gel bases with Poloxamer 407 and Carbomer 940 showed the best potential to prevent drug hydrolysis and improve chemical stability. Conclusions: Simple hydrogels with indomethacin did not show satisfactory physical and chemical stability, which justifies the use of more complex formulations such as emulgels. Furthermore, emul­gel with Poloxamer 407 exhibited potential for much longer shelf life than standard indomethacin semi-solid formulations.