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The goal of this investigation was to develop an in situ mucoadhesive ocular liposomal gel using Difluprednate prolonged-release drug delivery technology. Liposomal formulations were created using a Box-Behnken design to assess the effects of type and concentration of permeation enhancer, as well as the lecithin:cholesterol ratio, on entrapment efficiency, vesicle size, polydispersibility, and zeta potential. The optimum formulation had high entrapment efficiency (75.64%), appropriate vesicle size (110.3 nm) and polydispersibility (0.285), and desirable zeta potential (38.6 mv), with a 20% penetration enhancer and 4:1 lecithin to cholesterol ratio. Using this formulation, an in situ mucoadhesive gel was developed with gellan gum and Carbopol 934. The selected formulation (G2) demonstrated maximum viscosity (3864 cps) at physiological conditions, mucoadhesive force (0.395 N), and minimum viscosity (156 cps) at normal conditions. The release of Difluprednate was minimal (15.36%) after 30 minutes and maximal (69.82%) after 24 hours. Further testing for irritation and pharmacokinetics will be done on this formulation. The liposomal in situ gel was found to be non-irritating, have greater bioavailability, and demonstrate longer-lasting effects compared to the marketed product.

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