Effect of chitosan coating on the swelling and controlled release of a poorly water-soluble drug from an amphiphilic and pH-sensitive hydrogel

In the present work, a new particulate controlled release system was prepared, by coating alginate-g-PCL/Ca2+ beads with chitosan. The swelling behaviour and controlled release of a poorly water-soluble drug (theophylline) model were studied in media of varying pH, by simulating human fluids at 37 °C. In a simulated gastric fluid (SGF, pH 1.2), coated beads presented weak swelling (8–22%) and weak release rates (24–32% within 120 min), and were able to protect the drug from this harsh environment. In a simulated intestinal fluid (SIF, pH 6.8), the swelling rates of amphiphilic beads (before disintegration) were strongly reduced (300–1100%) comparatively with those of uncoated beads (700–1700%). This can be explained by the strong electrostatic interactions between the amino groups of chitosan and the carboxylate groups of alginate-g-PCL, leading to the formation of a protective membrane of strong polyelectrolyte complex around the beads. This outermost layer effectively promoted the stability of beads under gastro-intestinal tract conditions, while the hydrophobic interactions between theophylline and PCL grafts allowed a considerable slowing down of the drug release. It was found out that combination of the protective effect of the polyelectrolyte membrane in SIF associated with the hydrophobicity of PCL grafts allowed to release a poorly water-soluble drug, in a controlled manner, for 7 h, along a simulated gastro-intestinal tract.