The Utilization of Response Surface Methodology (RSM) In the Optimization of Diclofenac Sodium (DS) Liposomes Formulate through the Thin Film Hydration (TFH) Technique with Involving Computational Method

Objectives: The objective of the current studies to enhance the formulation of DS-loaded liposomes through the utilization of Response surface methodology (RSM) and involving the computation approach for their validation.

Methods: The optimization of DS-loaded liposomes was conducted using RSM, focusing of 2 main key parameters including encapsulation efficiency (% EE) and In-vitro drug release (% DR) for 12 hours via involving QbD. To formulate an optimize liposome formulation utilizing a 32 factorial design, with the phospholipid and cholesterol (CH) concentrations being the chosen independent variables. Nine formulations of DS-loaded liposomes were prepared using the TFH technique. The % EE, drug content, and in vitro release studies were assessed utilizing an Ultra Violet (UV)-visible spectrophotometer for λmax-275 nm. The evaluation included zeta potential, vesicle characterization, particle size and polydispersity index (PDI) of the best optimized DS formulation were evaluated. Lastly the involvement of computational tools, such as molecular dynamics simulations docking with COX-2 active site via Y385.

Results: The regression equations using RSM revealed that the phospholipid and CH molar concentration were significant variables in optimizing the percentage of % EE and percentage of drug release (% DR), with estimated coefficient values. The % EE was found to be 83.55±0.29, while the % DR was 71.22±0.34. The assumption of % DR and % EE values showed low % relative errors (PRE) of 0.069% and -0.194% respectively. The result shows that the design-developed model is appropriate for DS formulations and validates the model.

Conclusion: Investigational outcome represents the perceived responses were in related with the desired values and this represents the relationship of the RSM for optimization of % DR and % EE in DS loaded liposomal preparations.