Biopharmaceutical advancement of efonidipine hydrochloride ethanolate through amorphous solid dispersion of a Parteck SLC mesoporous silica polymer

Abstract

Amorphous solid dispersion is the most efficient method for improving the solubility and release of poorly water-soluble crystalline drug molecules. Efonidipine hydrochloride ethanolate (EFE) shows solubility-limited oral bioavailability (BCS class II). The present investigation aimed to improve the solubility, bioavailability, and therapeutic efficacy of EFE using Parteck® SLC mesoporous silica based amorphous solid dispersion (EFESD). EFESD was prepared by employing a solvent evaporation method. An optimized composition (1 : 1 ratio) of solid dispersion was subjected to in vitro, ex vivo, and in vivo characterization. The solubility of EFE in the EFESD form was found to be 5- and 4-fold improved in distilled water and phosphate buffer (pH 6.8), respectively. An ex vivo permeability study performed using different parts of the Wistar rat small intestine (the duodenum, jejunum, and ileum) using a non-everted sac method showed 2-fold improvements in the permeability of EFE in EFESD. Moreover, in vivo pharmacokinetic and pharmacodynamic studies performed using male Wistar rats showed 1.41- and 2.10-fold increase in the area under the curve and C_max, respectively, along with the improved anti-hypertensive activity of EFE in EFESD. Thus, amorphous solid dispersion with a novel applied Parteck® SLC 500 mesoporous silica formulation is an effective strategy to improve the biopharmaceutical properties of EFE.