FORMULATION, OPTIMIZATION AND CHARACTERIZATION OF BACLOFEN-LOADED LIPOSOMES FOR TOPICAL APPLICATION USING A QUALITY BY DESIGN APPROACH

Objective: The current study aimed to develop and optimize a liposomal gel for topical baclofen delivery to enhance skin permeation and therapeutic efficacy in muscle spasticity. Methods: A thin film hydration approach was used to create liposomes loaded with Baclofen. To optimize the baclofen liposomes, the effects of lipid concentration and hydration volume on vesicle size and entrapment efficiency were examined using a 32 full factorial design. A topical liposomal gel was created by incorporating an optimized baclofen liposome batch into a 1% Carbopol gel, and it was assessed for many parameters. Results: The optimized formulation demonstrated a mean vesicle size of 244.6 ± 3.34 with a PDI of 0.145 and an entrapment efficiency of 63.78 ± 2.66. The values from the experiments were very close to the predicted values given by the software, with a result error of ±5%, confirming the reliability of the statistical model at 95% confidence interval. A zeta potential of -28.8 mV for optimized formulation reflected good physical stability. The formulated liposomes were found to have a smooth surface texture with discrete particles in spherical shape as demonstrated in TEM analysis. The release profile of the drug from the liposomal gel formulation has shown a sustained release pattern up to 8 hrs with maximum release of 96.95%, following the Higuchi drug release kinetics model with non-Fickian diffusion as predicted by Kores-Peppas model. The in vivo skin irritation test conducted on Wistar rats revealed no signs of irritation. Furthermore, the histopathological evaluation established the safety of the formulation for topical application. Conclusion: It was concluded that the Baclofen-loaded topical liposomal gel represents a promising drug delivery approach for the treatment of muscle spasticity.