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

Author:

Wegmann Marcel1,Parola Luciano2,Bertera Facundo M2,Taira Carlos A23,Cagel Maximiliano34,Buontempo Fabian45,Bernabeu Ezequiel34,Höcht Christian2,Chiappetta Diego A34,Moretton Marcela A34

Affiliation:

1. Faculty of Medical and Life Sciences, Hochschule Furtwangen University, Baden-Württemberg, Germany

2. Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

3. National Science Research Council (CONICET), Buenos Aires, Argentina

4. Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

5. Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina

Abstract

Abstract Objectives Carvedilol (CAR) is a poorly water-soluble beta-blocker. Its encapsulation within nanomicelles (NMs) could improve drug solubility and its oral bioavailability, allowing the development of a paediatric liquid CAR formulation with commercially available copolymers: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplus®). Methods Drug-loaded NMs were prepared by copolymer and CAR dispersion in distilled water. Micellar size and morphology were characterized by dynamic light scattering and transmission electron microscopy, respectively. In-vitro drug permeation studies were evaluated by conventional gut sac method. In-vivo CAR oral bioavailability from NMs dispersions and drug control solution was evaluated 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 between 10.9 and 81.9 nm with a monomodal size distribution. There was a significant enhancement of CAR relative oral bioavailability for both copolymers vs a micelle-free drug solution (P < 0.05). This improvement was higher for TPGS-based micelles (4.95-fold) in accordance with the in-vitro CAR permeation results. Conclusions The present investigation demonstrates the development of highly concentrated CAR liquid micellar formulation. The improvement on drug oral bioavailability contributes to the potential of this NMs formulation to enhance CAR paediatric treatment.

Funder

University of Buenos Aires

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference54 articles.

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