Engineering a Physically Crosslinked N-Acetylcysteine Loaded Biopolymeric Hydrogel as a Sustained Topical Delivery Platform for Lamellar Ichthyosis

Lamellar ichthyosis is a rare inherited disorder of cornification marked by hyperkeratosis, scaling and impaired barrier function. This work aimed to develop a 5% w/w N-acetylcysteine (NAC) loaded sustained-release topical hydrogel prepared by ionic gelation, using chitosan and guar gum as polymers and sodium tripolyphosphate (STPP) as a physical cross-linker. Nine formulations (F1–F9) with increasing chitosan (0.01–0.08 g) and STPP (0.005–0.025 g) per 10 g batch were evaluated for appearance, pH, viscosity, spreadability, extrudability, washability, swelling, drug content, entrapment efficiency and in vitro release. Infrared spectroscopy showed no incompatibility between NAC and the excipients. All batches were smooth, homogeneous gels (pH 5.72–6.10; viscosity 4,200–6,510 mPa·s). Higher polymer and cross-linker levels lowered spreadability (8.6 to 4.9 g·cm/s), extrudability (95 to 80%) and 8 h drug release (83.5 to 68.0%). F5 (0.05 g chitosan, 0.02 g guar gum, 0.015 g STPP) was selected as optimum, with pH 6.01, viscosity 5,480 mPa·s, spreadability 6.9 g·cm/s, extrudability 90%, maximum swelling (140% at 5 h), drug content 94.1% and entrapment efficiency 94.92%. F5 released 75.0% of NAC in 8 h against 94.2% from a plain gel, and its release fitted the Higuchi model (R2 = 0.9995) with a Korsmeyer–Peppas exponent of 0.866, indicating diffusion with polymer relaxation. Scanning electron microscopy showed a porous, interconnected network. The cross-linked F5 hydrogel is a promising sustained-release topical platform for NAC that merits ex vivo, stability and clinical evaluation.