Novel carvedilol paediatric nanomicelle formulation:in-vitro characterization and in-vivo evaluation

Abstract

Objectives Carvedilol (CAR) is a poorly water-soluble beta-blocker. Its encapsu-lation within nanomicelles (NMs) could improve drug solubility and its oralbioavailability, allowing the development of a paediatric liquid CAR formulationwith commercially available copolymers: D-a-tocopheryl polyethylene glycol1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplusâ).Methods Drug-loaded NMs were prepared by copolymer and CAR dispersion indistilled water. Micellar size and morphology were characterized by dynamic lightscattering and transmission electron microscopy, respectively. In-vitro drug per-meation studies were evaluated by conventional gut sac method. In-vivo CARoral bioavailability from NMs dispersions and drug control solution was evalu-ated in Wistar rats.Key findings Carvedilol apparent aqueous solubility was increased (up to 60.4-folds) after its encapsulation within NMs. The micellar size was ranged between10.9 and 81.9 nm with a monomodal size distribution. There was a significantenhancement of CAR relative oral bioavailability for both copolymers vs amicelle-free drug solution (P < 0.05). This improvement was higher for TPGS-based micelles (4.95-fold) in accordance with the in-vitro CAR permeationresults.Conclusions The present investigation demonstrates the development of highlyconcentrated CAR liquid micellar formulation. The improvement on drug oralbioavailability contributes to the potential of this NMs formulation to enhanceCAR paediatric treatment.