Enhanced Bioavailability of Empagliflozin using Self-nanoemulsifying Drug Delivery System (SNEDDS): In vivo Pharmacokinetic Evaluation in rats

Abstract

Empagliflozin (EFZ), a sodium-glucose co-transporter 2 (SGLT2) inhibitor used to treat type 2 diabetes, faces challenges with poor solubility and bioavailability. This study aimed to evaluate a Self- Nanoemulsifying Drug Delivery System (SNEDDS), specifically SN1C, for enhancing EFZ’s dissolution rate and pharmacokinetics compared to pure EFZ powder and a marketed tablet (MKT). We assessed dissolution profiles in vitro and conducted pharmacokinetic studies in rats following oral administration of the three formulations. Plasma samples were analyzed using LC-MS/MS, and pharmacokinetic parameters were determined via non-compartmental analysis. SN1C demonstrated the highest dissolution rate in vitro. In vivo, SN1C achieved a significantly higher maximum plasma concentration (Cmax) and area under the curve (AUC(inf)) than EFZ and MKT, with approximately 1.5-fold higher Cmax and a significantly greater AUC(inf) (p < 0.05). Tmax and half-life (t1/2) were similar across all formulations, indicating that SNEDDS did not negatively impact these parameters. The results suggest that SN1C substantially improves the bioavailability of EFZ, highlighting the efficacy of SNEDDS technology in enhancing the oral delivery and therapeutic effectiveness of poorly soluble drugs like EFZ.