Central Composite Design-Based Optimization and Formulation ofCapecitabine Nanosuspension for Improved Gastric Cancer Therapy

Objective:: To formulate, design, and evaluate a stable and optimized nanoscale suspension of the anticancer drug Capecitabine using Central Composite Design (CCD) optimization, harnessing the benefits of nanoparticle drug delivery systems to enhance gastric cancer therapy and address the limitations of conventional treatment methods. Methods:: The nanosuspension of capecitabine was developed based on the trial runs suggested by the Central Composite Design (CCD) using statistical software, involving a total of 13 experimental runs. Chitosan and Pluronic F-68 were selected as the independent variables. The nanosuspension was prepared using an ultrasonication technique and evaluated for various parameters, including particle size, zeta potential, entrapment efficiency, drug content percentage, in-vitro drug release, and anti-cancer effectiveness. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies were conducted to examine the crystalline nature of capecitabine within the formulations. An overlay plot and perturbation study were utilized to optimize the nanosuspension formulation. Results:: The study assessed the impact of various factors on key responses, namely particle size (nm), entrapment efficiency (%), and drug release at 8 hours (%). Through the analysis, a polynomial equation was employed to optimize the formulation, considering the significance levels indicated by the p-values. Notably, these variables demonstrated a substantial influence on the responses. The comparison between observed and predicted values revealed a relatively minor variance (72.3, 239.3, and 79.34 for particle size, entrapment efficiency, and percentage drug release at 8 hours, respectively), indicating the suitability of the model. Discussion:: Moreover, it was observed that the prepared nanosuspension demonstrated compatibility with the used excipients, with capecitabine-entrapped nanoparticles uniformly dispersed within the suspending medium. Conclusion:: The study evaluated the impact of various factors on key responses, specifically particle size (nm), entrapment efficiency (%), and drug release at 8 hours (%). Using a polynomial equation for optimization, the significance of variables was determined by their p-values, revealing a substantial influence on the responses. The comparison between observed and predicted values showed minimal variance (particle size: 239 nm, entrapment efficiency: 72.3%, and drug release at 8 hours: 79.37%), confirming the Model accuracy. Additionally, the prepared nanosuspension showed compatibility with the used excipients, with uniformly dispersed capecitabineentrapped nanoparticles within the suspending medium. Further in vivo studies are necessary to validate these findings.