Shardul BUGADI, Vasudev KOLI, Utkarsha SHIVSHARAN, Vilas MOTE
Journal of Research in Pharmacy - 2026;30(2):482-502
Intranasal administration offers a promising non-invasive route for drug delivery, particularly for targeting the central nervous system (CNS). Clonazepam, an antiepileptic and anxiolytic benzodiazepine, faces challenges with low oral bioavailability due to poor water solubility and extensive first-pass metabolism. To address these issues, a liposomal in-situ nasal gel formulation was developed with the objective of improving brain targeting and achieving sustained drug release. Liposomes loaded with clonazepam were prepared using the thin-film hydration technique and optimized via Central Composite Design (CCD) by adjusting soya lecithin and cholesterol quantities. Key responses evaluated were entrapment efficiency (%EE) and drug release at 8 hours (%DR). The optimized liposomes were then incorporated into a thermo- and pH-responsive in-situ gel using Poloxamer 407 and Carbopol 934, further fine-tuned for drug content and release. Characterization included particle size, zeta potential, FTIR, TEM, viscosity, muco-adhesion, and in vitro diffusion. The optimized liposomal batch (L5) showed an EE of 79.80% and 73.72% drug release over 8 hours, with vesicles approximately 380 nm in size and a zeta potential of -46.35 mV, indicating stability. Drug release followed a zero-order kinetic model with Super Case-II transport. The final optimized gel (L5G4) exhibited a drug content of 71.68% and an 83.09% release rate. Gelling time was measured at 33 dereceC, which was chosen to simulate the physiological temperature of the nasal cavity, ensuring relevance to in-vivo conditions. The gel also demonstrated optimal viscosity and mucoadhesive properties. Statistical validation confirmed the formulation's reliability. This liposomal in-situ gel enhances intranasal delivery of Clonazepam, offering sustained release and improved potential for patient adherence compared to conventional forms. While brain targeting was a primary objective of this formulation design, direct experimental data supporting enhanced brain targeting were not presented in this study, which represents a limitation.
