Use of ordered mesoporous silica-loaded phyto-phospholipid complex for BCS IV class plant drug to enhance oral bioavailability: a case report of tanshinone IIA

Abstract

This work aimed to improve membrane permeability as well as in vitro dissolution rate and thus enhance oral bioavailability for a BCS IV class plant drug by constructing a combined drug delivery system (CDDS) composed of a phospholipid complex (PC) and an ordered mesoporous silica-based solid dispersion (SD), using tanshinone II_A (TS) as a model drug. Tanshinone II_A phospholipid complex (TS–PC) and ordered mesoporous silica-based solid dispersion (TSPC-SD) were prepared using the solvent evaporation method. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy proved the formation of TS–PC or TSPC-SD, and amorphous form existing in these two systems. n-Octanol/water partition coefficient (lg P_o/w) tests showed that a remarkably decreased lg P_o/w for TS–PC was obtained compared to unformulated TS, while no increase was observed for TSPC-SD compared to TS–PC. Evaluations in Caco-2 cell monolayers revealed that TS–PC exhibited a significantly increased absorptive permeability (p < 0.05) in apparent permeability coefficients (P_app) (70.2% higher) compared to unformulated TS. Compared to that of unformulated TS, in vitro drug dissolution rate of TS from TSPC-SD significantly increased (p < 0.01), while that from TS–PC was slightly decreased. Pharmacokinetic studies demonstrated that TSPC-SD had 2.19-fold higher AUC_0–t compared to unformulated TS (p < 0.01). The remarkable improvements in bioavailability with the use of TSPC-SD may result from comprehensive effects, including improved lg P_o/w and P_appvia PC, and increased dissolution rates from SD. These results indicated that the CDDS can be promising for enhancing the oral bioavailability of BCS IV class drugs.