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.
