Preparation, characterization and release of verapamil hydrochloride from polycaprolactone/acrylic acid (PCL/AA) hydrogels

Pak J Pharm Sci. 2011 Oct;24(4):503-11.

Abstract

In this study pH sensitive, biocompatible and controlled released hydrogels were prepared and their localized drug delivery effect was analyzed. Polycaprolactone and acrylic acid (PCL/AA) were reacted by free radical polymerization and developed inter penetrating polymeric network (IPN) hydrogels. Benzylperoxide was used as initiator and N, N methylenebisacrylamide [NNMBisAm] was employed as a cross-linking agent. Different concentrations of monomer, polymer and cross-linking agent were used and the reaction parameters were optimized. The obtained PCL/AA hydrogels were fully characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) that determined the polymer structure, its morphology and strength respectively. Verapamil, a calcium channel blocker was loaded by incubation of polymerization method. Controlled release Verapamil hydrogel was developed due to its low solubility; low permeability and having very short half life of 1.2-2 h. The dynamic swelling, equilibrium swelling and drug release were carried out in a buffer solution of pH 1.2, 4.5 and 6.8. Concentration of Acrylic acid showed direct, while Polycaprolactone inverse relation to swelling and drug release due to their hydrophilic and hydrophobic nature respectively. Cross-linking agent also had the contrary effect on swelling. Diffusion coefficient (D) of hydrogels was determined by using Flory-Rehner theory. Drug release and swelling data were analyzed by different kinetic models, like Zero order, First order, Higuchi, Korsmeyer's and Peppas. The release and diffusion was best described by the first order kinetics where n value was <0.5 for all the formulations indicating Fickian drug release mechanism.

MeSH terms

  • Acrylamides / chemistry
  • Acrylates / chemistry*
  • Biological Availability
  • Buffers
  • Delayed-Action Preparations / chemical synthesis
  • Delayed-Action Preparations / chemistry
  • Hot Temperature
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Microscopy, Electron, Scanning
  • Polyesters / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • Surface Properties
  • Verapamil / administration & dosage*
  • Verapamil / pharmacokinetics*
  • Water / chemistry

Substances

  • Acrylamides
  • Acrylates
  • Buffers
  • Delayed-Action Preparations
  • Hydrogels
  • Polyesters
  • Water
  • polycaprolactone
  • Verapamil
  • N,N'-methylenebisacrylamide
  • acrylic acid