Evaluation of mixed matrices of chitosan and fatty-acids filled into hard gelatin capsules as sustained-release hydrodynamically balanced systems

Abstract

The aim of this study was to utilize electrostatic interaction between chitosan (CS) and fatty-acids (FA) in designing mixed matrices filled into hard gelatin capsules as hydrodynamically balanced systems with slow drug-release. CS of low and high molecular weight (Mwt), lauric acid (LA), stearic acid (SA) and palmitic acid (PA) were used for this purpose. Riboflavin, known to have narrow absorption window in the upper gastrointestinal tract, was used as a model drug.The interaction of CS with each FA was evaluated by kneading effervescent (Eff.) or non-effervescent (non-Eff.) CS-FA mixtures using 0.1 M HCl. The mixtures differed with respect to CS Mwt, FA type and CS:FA weight ratio. Upon drying, the mixtures were evaluated for CS-FA interaction using Fourier transform infrared spectroscopy (FT-IR). Eff. and non-Eff. mixtures of optimal CS:FA ratio for the interaction containing riboflavin were prepared as granulations and filled into hard gelatin capsules. The capsules were observed for flotation of their matrices and studied for drug-release in 0.1 M HCl.Evident interaction between CS and each FA was demonstrated in 0.1 M HCl, irrespective of CS Mwt. However, drug-release was highly affected by CS Mwt and FA type and was the slowest for low Mwt CS and LA as Eff. matrix or PA as non-Eff. matrix. The flotation of these matrices was rapid and prolonged (>6 h).