Formulation and Evaluation of Self Nanoemulsifying Drug Delivery System of Sitagliptin and Metformin

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder requiring effective long-term glycemic control. Sitagliptin and Metformin Hydrochloride are widely used in combination therapy; however, both drugs exhibit limitations such as poor solubility and variable oral bioavailability, which can affect therapeutic efficacy. The present study aimed to develop and evaluate a liquid self-nanoemulsifying drug delivery system (SNEDDS) for the co-delivery of Sitagliptin and Metformin Hydrochloride to enhance their solubility, dissolution rate, and potential oral bioavailability. SNEDDS formulations were prepared using various combinations of oils, surfactants, and co-surfactants, followed by optimization based on emulsification efficiency, droplet size, polydispersity index (PDI), zeta potential, and drug content. Preformulation studies confirmed suitable excipients, with Garlic oil as the lipid phase and Cremophor EL and PEG 400 as effective surfactant and co-surfactant systems. The optimized formulations exhibited droplet sizes in the nanometric range (48–102 nm), acceptable PDI values, and zeta potential indicating moderate stability. Drug content analysis showed uniform incorporation of both drugs, and robustness to dilution confirmed formulation stability. In vitro diffusion studies demonstrated enhanced drug release, with cumulative release reaching up to 96.89% for Sitagliptin and 96.01% for Metformin over 12 hours. The results indicate that SNEDDS significantly improved the dissolution behavior of both drugs compared to conventional formulations. Overall, the developed SNEDDS presents a promising strategy for improving the oral delivery and therapeutic performance of Sitagliptin and Metformin Hydrochloride in T2DM management.

Keywords: Sitagliptin, Metformin, Self-Nanoemulsifying Drug Delivery System (SNEDDS), Droplet Size, Polydispersity Index, Zeta Potential, Solubility Enhancement, Cardiovascular Diseases, Oral Bioavailability, In Vitro Drug Release.