Development and evaluation of empagliflozin-loaded solid lipid nanoparticles: Pharmacokinetics and pharmacodynamics for oral delivery

Abstract

Type 2 diabetes mellitus is frequently treated with empagliflozin (EZN), a sodium-glucose cotransporter 2 inhibitor. Solid lipid nanoparticles (SLNs) shield the drug from gastrointestinal breakdown and improve the bioavailability of lipophilic drugs. The aim of the study is to use SLNs to enhance EZN's pharmacokinetics and pharmacodynamics in the treatment of diabetes mellitus. To prepare EZN-loaded SLNs, central composite design (CCD) was employed. The optimized batch (optimized EZN-loaded SLNs) had the desired values of dependent variables Vesicle size (R1), Entrapment Efficiency (R2), and Cumulative Drug Release (CDR) (R3). This was achieved by using analysis of variance (ANOVA) to analyse independent variables such as lipid concentration (X1), surfactant concentration (X2), sonication time (X3), and homogenization speed (X4). F8 exhibited the highest drug entrapment (90.6% ± 2.8%), CDR (89.2 ± 3.6), and average particle size (98.6 ± 2.1 nm) among the 30 distinct formulated formulae (F1-F30). Based on the F-value and p-value, the model was determined to be significant for particle size, entrapment efficiency, and CDR. The actual values of particle size entrapment efficiency and CDR closely matched the projected values of the optimized batch. The in vitro release trials produced a burst release followed by a continuous release. When compared to the EZN solution, the relative bioavailability of EZN-loaded SLNs was 1.2 times higher, indicating superior protection against the gastrointestinal environment. In rats with streptozotocin-induced diabetes mellitus, the optimized EZN-loaded SLNs outperformed the basic drug suspension in terms of antidiabetic efficacy. One promising method for administering EZN in the treatment of diabetes mellitus is by SLNs.

Keywords

Solid lipid nanoparticles / Pharmacokinetics / Bioavailability / Homogenization / Central composite design / Oral formulation

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