In vitro and in vivo evaluation of pirfenidone loaded acrylamide grafted pullulan-poly(vinyl alcohol) interpenetrating polymer networks.

Highlights • Application of acrylamide grafted pullulan as one of the component for controlled release drug delivery system. • Detailed thermal kinetic profile of microsphere using isoconversional model. • In vitro enzymatic degradation of microsphere. • Biocompatibility assessment of microsphere in human hepatocellular carcinoma cell line. • Comparative in vivo pharmacokinetic study of optimized formulation with marketed product. Abstract The aim of present study was to develop controlled release formulation of pirfenidone using acrylamide grafted pullulan. Interpenetrating polymer network (IPN) microspheres were prepared using acrylamide grafted pullulan and PVA utilizing glutaraldehyde assisted water-in-oil emulsion crosslinking method. IPN microspheres were characterized by FTIR, solid state 13C NMR and XRD spectroscopy. In vitro enzymatic degradation study showed 34.30% degradation after 24 h with degradation rate constant of 0.0088 min−1. In vitro biocompatibility test showed no changes in cellular morphology and cell adherence to microspheres, indicating its biocompatible nature. The release exponent value of all formulations was less than 0.45, indicating the release mechanism to be Fickian diffusion. Finally, in vivo pharmacokinetic study showed longer T max (1.16 h) and greater AUC value (10037.76 ng h/mL,) as compared to Pirfenex® (T max = 0.5 h; AUC = 4310.45 ng h/mL,). The results indicated that the prepared formulation could successfully control the drug release for prolonged time period. [ABSTRACT FROM AUTHOR]