Optimization of self-microemulsifying drug delivery system for phospholipid complex of telmisartan using D-optimal mixture design

Abstract

To improve the dissolution behavior of telmisartan (TMS), a poorly water-soluble angiotensin II receptor blocker, TMS-phospholipid complex (TPC) was prepared by solvent evaporation method and characterized by differential scanning calorimetry and powder X-ray diffractometry. The crystalline structure of TMS was transited into an amorphous state by TPC formation. The equilibrium solubility of TPC (1.3–6.1 mg/mL) in various vehicles was about 100 times higher than that of TMS (0.009–0.058 mg/mL). TPC-loaded self-microemulsifying drug delivery system (SMEDDS) formulation was optimized using the D-optimal mixture design with the composition of 14% Capryol 90 (oil; X 1 ), 59.9% tween 80 (surfactant; X 2 ), and 26.1% tetraglycol (cosurfactant; X 3 ) as independent variables, which resulted in a droplet size of 22.17 nm (Y 1 ), TMS solubilization of 4.06 mg/mL (Y 2 ), and 99.4% drug release in 15 min (Y 3 ) as response factors. The desirability function value was 0.854, indicating the reliability and accuracy of optimization; in addition, good agreement was found between the model prediction and experimental values of Y 1 , Y 2 , and Y 3 . Dissolution of raw TMS was poor and pH-dependent, where it had extremely low dissolution (< 1% for 2 h) in water, pH 4, and pH 6.8 media; however, it showed fast and high dissolution (< 90% in 5 min) in pH 1.2 medium. In contrast, the dissolution of the optimized TPC-loaded SMEDDS was pH-independent and reached over 90% within 5 min in all the media tested. Thus, we suggested that phospholipid complex formation and SMEDDS formulation using the experimental design method might be a promising approach to enhance the dissolution of poorly soluble drugs. © 2018 Son et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.