Formulation, Optimization and Evaluation of In-Situ Nasal Gel Loaded with Clonazepam Liposomes

Intranasal administration provides a promising alternative to oral and injectable methods, especially for targeting the central nervous system (CNS). Clonazepam, a benzodiazepine used for treating epilepsy and anxiety, has low oral bioavailability due to its poor water solubility and extensive first-pass metabolism. A liposomal in-situ nasal gel formulation was created to improve brain targeting and sustain drug release, addressing this issue. Liposomes containing clonazepam were created using the thin-film hydration technique and optimized through Central Composite Design (CCD), adjusting the amounts of soya lecithin and cholesterol. Key responses included entrapment efficiency (%EE) and drug release at 8 hours (%DR). Using Poloxamer 407 and Carbopol 934, the optimized liposomes were integrated into a thermo- and pH-responsive in-situ gel, which was further fine-tuned for drug content and release. The characteristics of the formulation were determined for size, zeta potential, FTIR, TEM, viscosity, muco-adhesion, and in vitro diffusion. The liposomal batch (L5) that was optimized exhibited an EE of 79.80% and a drug release of 73.72% over the course of 8 hours. The vesicles measured approximately 380 nm and had a zeta potential of -46.35 mV, which suggests stability. The drug release adhered to a zero-order kinetic model and exhibited Super Case-II transport characteristics. The final gel (L5G4) demonstrated a drug content of 71.68% and a release rate of 83.09%, gelling at approximately 33°C while exhibiting optimal viscosity and mucoadhesive characteristics. Reliability of the formulation was confirmed through statistical validation. The produced liposomal in-situ gel boosts intranasal delivery of Clonazepam, providing sustained release, better brain targeting, and potential for greater patient adherence compared to traditional forms.