Development and in vitro tuning of empagliflozin-containing dissolvable microneedle patch for enhanced transdermal delivery.

Abstract

This painless method allows drugs to penetrate the outer skin layer, offering several advantages over alternative administration routes, including ease of use and the ability to bypass enterohepatic circulation. Among transdermal drug delivery systems (TDDS), microneedle patches (MNPs) are emerging as an innovative approach for minimally invasive drug delivery, enhancing the skin permeation of substances ranging from macro to micro sizes. This study explores dissolvable microneedle patches (dMNPs) as a novel method to improve the systemic delivery of empagliflozin, an SGLT-2 inhibitor, commonly used to manage type 2 diabetes mellitus (T2DM). However, its oral administration poses challenges due to rapid absorption, variable bioavailability, and a moderate half-life that necessitates frequent dosing. The microneedle patches were manufactured using a mold-based solvent casting technique, utilizing a polymer-drug combination that dissolves upon skin application. The development of the dMNPs involved polyvinylpyrrolidone and polyvinyl alcohol. Characterization of the formulated dMNPs included scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), dissolution testing, tensile strength analysis, percentage elongation measurement, mechanical strength assessment, and skin irritation studies. The optimized dMNP formulation (MP6) exhibited notable characteristics such as sharp, uniform, pyramid-shaped needles, stability at elevated temperatures, crystalline structures of the drug and polymers, controlled weight loss upon heating, effective drug dissolution, optimal tensile strength, penetration depth, moisture content, elongation capability, and a favorable release rate. In vitro release demonstrated the enhanced properties of the dissolvable microneedle patches, with zero-order kinetics identified as the most suitable model for MP6 based on regression coefficient analysis. Overall, the characterization studies, in vitro skin irritation evaluation, confirmed the stability and biocompatibility of the optimized dMNPs, making them suitable for transdermal application.