The aim of this study was to improve the oral bioavailability of a practically insoluble drug, efonidipine hydrochloride (EFH), by agglomeration in acid solution/gastric fluid. The EFH nanosuspension was prepared by the wet-milling method with F68 as a dispersing agent, SDS as an auxiliary stabilizer and l-arginine as a pH adjusting agent. The EFH nanosuspension have been prepared in industrial scale-up. The dissolution rate of the EFH nanosuspension was greater than that of bulk EFH. An in vitro intestinal permeability study showed a clear increase in the apparent permeability of different intestinal segments compared with bulk EFH. Also, a pharmacokinetic study showed that the Cmax and AUC0-24h of the nanosuspensions were approximately 1.76-fold and 2.2-fold greater than that of bulk EFH, respectively, and there was no significant difference compared with commercial tablets. It appears that wet-milling offers an effective approach to improve the dissolution rate and oral absorption of this practically insoluble drug.
Keywords: Efonidipine hydrochloride; Intestinal permeability; Nanosuspensions; Pharmacokinetics; Wet-milling method.
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