Poly(vinyl alcohol) and poly(acrylic acid) sequential interpenetrating network pH-sensitive microspheres for the delivery of diclofenac sodium to the intestine

Sequential interpenetrating network (IPN) of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) were prepared and crosslinked with glutaraldehyde (GA) to form pH-sensitive microspheres by the water-in-oil (w/o) emulsification method. Microspheres were used to deliver a model anti-inflammatory drug, diclofenac sodium (DS), to the intestine. The formed IPN was analyzed by Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses were done on the drug-loaded microspheres to confirm the polymorphism of DS. Results indicated a molecular level dispersion of DS in the IPN. Microspheres formed were spherical with the smooth surfaces as evidenced by scanning electron microscopy (SEM). Particle size and size distribution was studied using laser light diffraction particle size analyzer. Particle size analysis was also done by optical microscope for the selected microspheres; the change in diameter of the microspheres when soaked in different media at different time intervals was measured by optical microscope. Microspheres showed a pulsatile swelling behavior when the pH of the swelling media was changed. The swelling data were fitted to an empirical equation to understand the phenomenon of water transport as well as to calculate the diffusion coefficient (D). Values of D in acidic media were lower than those found in basic media. The values of D decrease with increasing crosslinking of the matrix. In-vitro release studies have been performed in 1.2 and 7.4 pH media to simulate gastric and intestinal conditions. The results indicated a dependence on the PH of the release media, extent of crosslinking and the amount of drug loading. (C) 2004 Elsevier B.V. All rights reserved.