Development and Evaluation of a Novel Full-Interpenetrating Polymer Network-Based Hydrogel for Colon-Targeted Release...

Ornidazole is an antiprotozoal and antibacterial agent used to treat intestinal infections. However, its clinical use is limited by modest first-pass metabolism and poor aqueous solubility. These characteristics make it a suitable candidate for incorporation into a pH-responsive interpenetrating polymer network (IPN) hydrogel system for potential colon-targeted delivery. This study aimed to prepare, characterize, and evaluate chitosan-polyacrylic acid IPN composite hydrogels as carriers for ornidazole.

Chitosan-polyacrylic acid IPN composite hydrogels incorporating ornidazole were prepared using N, N'-methylene bisacrylamide and glutaraldehyde as cross-linking agents. Polymer formation, drug entrapment, and drug-polymer interactions were investigated using Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). These analyses confirmed successful polymer formation and the absence of significant chemical alterations in the entrapped drug. The hydrogels were further evaluated for swelling behavior and in vitro drug release. Morphological changes before and after dissolution were examined using Scanning Electron Microscopy (SEM).

The hydrogels exhibited a production yield of 86.39 ± 4.23% and drug loading of 92.39 ± 2.16%. They demonstrated pronounced pH-sensitive swelling behavior, showing minimal swelling under acidic conditions and rapid swelling in alkaline media. In vitro release studies indicated that drug release was dependent on hydrogel swelling and followed a biphasic release pattern with non-Fickian diffusion kinetics at higher pH values. SEM analysis of the optimized formulation revealed the formation of large, open channel-like pores after dissolution.

The synthesized chitosan-polyacrylic acid IPN hydrogels showed high production yield and drug loading with stable physicochemical characteristics. Their pH-dependent swelling and release behaviour confirmed minimal drug release in acidic media and enhanced release at intestinal/colonic pH. Formulation F9 was identified as the optimized formulation. FTIR, DSC, and XRD analyses confirmed successful IPN formation and amorphous dispersion of ORNI without chemical incompatibility. Overall, the system demonstrated effective controlled, colon-targeted delivery potential for improving the oral bioavailability of Ornidazole. However, further studies including biological evaluation and in vivo validation are required to confirm colontargeting efficiency.

Chitosan-polyacrylic acid IPN hydrogel with its biodegradable nature and pH-sensitive release of ornidazole is an attractive option to be further explored for targeted controlled drug delivery formulations for the drug.