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

作者：Wegmann Marcel; Parola Luciano; Bertera Facundo M; Taira Carlos A; Cagel Maximiliano; Buontempo Fabian; Bernabeu Ezequiel; Hocht Christian; Chiappetta Diego A; Moretton Marcela A

来源：Journal of Pharmacy and Pharmacology, 2017, 69(5): 544-553.

DOI：10.1111/jphp.12605

• carvedilol
• nanomicelles
• nanotechnology
• oral bioavailability
• paediatric pharmacotherapy

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-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly (ethylene glycol) (Soluplus (R)).
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 60.4folds) 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 TPGSbased 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.

• 出版日期2017-5