Comprehensive Characterization and in Vitro Performance Evaluation of Acetazolamide-Loaded Self-Microemulsifying Drug Delivery System for Enhanced Dissolution

Abstract

Acetazolamide is a poorly soluble drug whose limited aqueous solubility can restrict its dissolution and oral drug delivery performance. The present study aimed to develop and comprehensively characterize acetazolamide-loaded self-microemulsifying drug delivery systems (SMEDDS) and compare the performance of liquid SMEDDS (L-SMEDDS) with its solidified form (S-SMEDDS). An optimized L-SMEDDS was developed using Capryol® 90 as oil, Cremophor® RH 40 as surfactant, and Transcutol® HP as co-surfactant. The formulation was optimized using a Box–Behnken experimental design considering globule size, polydispersity index (PDI), and transmittance as critical responses. The optimized L-SMEDDS exhibited a globule size of 78.4 nm, PDI of 0.221, transmittance of 96.8%, self-emulsification time of 20.3 s, and drug content of 98.6%. The optimized liquid formulation was converted into S-SMEDDS using Aerosil® 200 as a solid carrier by spray drying. The resulting S-SMEDDS showed satisfactory micromeritic properties and rapid reconstitution, producing globules of 80.6 nm with a PDI of 0.231. FTIR, DSC, and PXRD studies indicated compatibility between acetazolamide and the formulation components and reduced crystallinity of the drug following formulation. TEM analysis revealed predominantly spherical and uniformly distributed globules without prominent aggregation. In-vitro dissolution studies demonstrated markedly enhanced drug release from both SMEDDS formulations compared with pure acetazolamide. After 60 min, cumulative drug release was 96.8% for L-SMEDDS, 91.4% for S-SMEDDS, and 38.5% for pure acetazolamide. Release kinetic analysis showed the highest correlation with the Higuchi model, while the Korsmeyer–Peppas model indicated Fickian diffusion for L-SMEDDS. Both formulations maintained satisfactory physicochemical characteristics during 3 months of stability evaluation, although slightly greater changes were observed under accelerated conditions, particularly for S-SMEDDS. Overall, the findings demonstrate that SMEDDS, particularly the optimized liquid system, substantially enhanced the dissolution performance of acetazolamide and provided a promising formulation approach for improving its oral delivery characteristics.