Development Of A Box–Behnken Design Optimized Linagliptin Liposphere Formulation For Improved Bioavailability And Sustained Release

Abstract

The present study aimed to develop and optimize Linagliptin-loaded lipospheres for sustained drug delivery using a Box–Behnken Design (BBD). Stearic acid, cetyl alcohol, and Tween 80 were selected as independent variables, while entrapment efficiency and particle size were taken as response variables. Fifteen experimental runs were performed, and the formulations were evaluated for percentage yield, entrapment efficiency, particle size, zeta potential, polydispersity index (PDI), and flow properties. Among the prepared formulations, F15 was identified as the optimized batch, exhibiting the highest percentage yield (86.65%), maximum entrapment efficiency (81.15%), and minimum particle size (220.12 nm). The zeta potential (–36.25 mV) and PDI (0.336) confirmed good physical stability and narrow size distribution. Scanning electron microscopy revealed spherical and smooth-surfaced lipospheres. The in vitro drug release study of F15 displayed a biphasic pattern with 97.45% cumulative release at 10 hours, following zero-order kinetics (R² = 0.9957) and non-Fickian diffusion as per the Korsmeyer–Peppas model (R² = 0.9869). Stability studies indicated that refrigerated storage (4 ± 2°C) maintained particle size, PDI, and entrapment efficiency more effectively compared to ambient conditions (25 ± 3°C / 65 ± 5% RH). The optimized Linagliptin lipospheres demonstrated promising potential as a controlled-release oral drug delivery system with improved drug encapsulation, stability, and sustained release characteristics. These findings suggest that liposphere-based delivery of Linagliptin could enhance therapeutic efficacy and patient compliance in the management of type 2 diabetes mellitus.