Carvedilol-loaded nanocapsules: Mucoadhesive properties and permeability across the sublingual mucosa

Eur J Pharm Biopharm. 2017 May:114:88-95. doi: 10.1016/j.ejpb.2017.01.007. Epub 2017 Jan 22.

Abstract

Carvedilol is a drug used to treat heart failure, hypertension, and coronary artery diseases . However, it has low oral bioavailability (25-35%) due to its high first-pass hepatic metabolism. The objective of this study was to develop carvedilol-loaded mucoadhesive nanocapsules as delivery systems for the sublingual administration of the drug. Nanocapsules were prepared using poly(ε-caprolactone) (CAR-LNC) and Eudragit® RS 100 (CAR-NC) as polymeric wall. In vitro interaction of formulations with mucin was performed to predict their mucoadhesion capacity. The permeability and washability profiles of carvedilol were evaluated using porcine sublingual mucosa. The mean diameter of particles in formulations was in the nanometric range, and particles had low polydispersity and slightly acidic pH. Zeta potential values were positive for CAR-NC and negative for CAR-LNC. Encapsulation efficiency was higher than 87% and 99% for CAR-NC and CAR-LNC, respectively. Both formulations presented controlled drug release profiles and mucoadhesive properties. Carvedilol was able to permeate through the sublingual mucosa. Nanoencapsulation improved retention time on the mucosa and permeation in presence of simulated salivary flux. This study highlighted the suitability of using CAR-loaded nanocapsules in the development of innovative sublingual dosage forms.

Keywords: Carvedilol; Eudragit® RS 100; Mucoadhesion; Nanocapsules; Poly(ε-caprolactone); Sublingual permeability.

MeSH terms

  • Acrylic Resins
  • Administration, Sublingual
  • Animals
  • Carbazoles / administration & dosage*
  • Carbazoles / pharmacokinetics*
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / pharmacokinetics*
  • Carvedilol
  • Delayed-Action Preparations
  • Drug Compounding
  • Excipients
  • In Vitro Techniques
  • Mouth Mucosa / metabolism
  • Nanocapsules
  • Permeability
  • Polyesters
  • Polymethacrylic Acids
  • Propanolamines / administration & dosage*
  • Propanolamines / pharmacokinetics*
  • Swine
  • Tissue Adhesives

Substances

  • Acrylic Resins
  • Carbazoles
  • Cardiovascular Agents
  • Delayed-Action Preparations
  • Excipients
  • Nanocapsules
  • Polyesters
  • Polymethacrylic Acids
  • Propanolamines
  • Tissue Adhesives
  • Carvedilol
  • polycaprolactone
  • methylmethacrylate-methacrylic acid copolymer
  • Eudragit RS