Carvedilol-loaded nanocapsules : physicochemical characterization and in vitro drug release

Abstract

Carvedilol (CV) has been used for the management of heart failure, hypertension and coronary artery diseases. However, it presents low oral bioavailability (25-35%). The objective of this study was to develop carvedilol-loaded nanocapsules (NC) in order to achieve a controlled drug release aiming the development of dosage forms to be administered by alternative routes. Poly(ε-caprolactone) (PCL) and Eudragit RS100 (EUD) were evaluated as polymeric wall. Nanocapsules (CV-PCL-NC and CV-EUD-NC) were prepared by interfacial deposition of preformed polymer method and characterized according to particle size and polydispersity, zeta potential, pH, drug content, encapsulation efficiency, morphology, backscattering analysis, presence of nanocrystals and drug release profile. Thermal analysis was performed to evaluate compatibility between CV and excipients. All formulations showed nanometric diameters with low polydispersity and pH slightly acid The zeta potential was positive and negative for CV-EUD-NC and CV-PCL-NC, respectively. The drug content was close to theoretical value (0.5 mg.mL-1) for both formulations and the encapsulation efficiency was higher than 87% and 99% for CV-EUD-NC and CV-PCL-NC, respectively. Nanocapsules were spherical-shaped and their suspensions showed no significant phenomena of physical instability. Drug release was controlled by both developed formulations. However, CV-PCL-NC showed phase separation during storage and an interaction between the drug and the surfactant was evidenced by thermal analysis. This study demonstrated the feasibility to encapsulate CV in nanocapsules to achieve a controlled release rate. Further studies will be carried out to explore alternatives routes of administration using these formulations.