pH sensitive polyelectrolyte complex of O-carboxymethyl chitosan and poly (acrylic acid) cross-linked with calcium for sustained delivery of acid susceptible drugs

Int J Pharm. 2012 Oct 15;436(1-2):418-25. doi: 10.1016/j.ijpharm.2012.07.016. Epub 2012 Jul 17.

Abstract

The present study investigates the ability of a polyelectrolyte complex, composed of O-carboxymethyl chitosan (O-CMC) and carbopol cross linked with calcium, as a pH-sensitive carrier for acid susceptible drugs. DSC studies were performed to confirm the formation of O-CMC-carbopol complex. Double endothermic peaks in thermogram of polyelectrolyte beads reflect the molecular changes brought in after cross-linking. FT-IR spectroscopy was used to reveal peak variation of the carboxylic groups as a function of pH 1.2 and pH 6.8. The formation of polyelectrolyte complex, on account of electrostatic interactions between the COO(-) group of carbopol and the NH(3)(+) group of O-CMC, was also confirmed by FT-IR studies. Swelling of the O-CMC-carbopol film showed a pH-dependent profile that was affected by calcium ion concentration. The swelling rate was more significant at intestinal pH because the ionization of carboxylic acid group on O-CMC and carbopol creates electrostatic repulsion. Release behavior of drug is relative to the viscosity of solution and the ionic interaction between O-CMC and carbopol. Mucous glycoprotein assay revealed that ionization of carboxylic group on the beads at intestinal pH formed a strong hydrogen bond with mucin, which was responsible for the prominent mucoadhesive property thus prolonging the intestinal residence time.

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / chemistry
  • Acrylic Resins / chemistry*
  • Animals
  • Calcium / chemistry*
  • Calorimetry, Differential Scanning
  • Chitosan / analogs & derivatives*
  • Chitosan / chemistry
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry*
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa / chemistry
  • Male
  • Mucins / chemistry
  • Polyvinyls / chemistry
  • Rabeprazole
  • Rats
  • Rats, Wistar
  • Spectroscopy, Fourier Transform Infrared

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Acrylic Resins
  • Delayed-Action Preparations
  • Drug Carriers
  • Mucins
  • O-carboxymethylchitosan
  • Polyvinyls
  • carboxypolymethylene
  • Rabeprazole
  • carbopol 940
  • Chitosan
  • Calcium