Formulation, Optimization and Design of Capecitabine Nanosuspension to Enhance the Anti-Gastric Cancer Efficacy using...

Capecitabine is an anticancer antimetabolite of fluorouracil that inhibits cell proliferation and impairs DNA repair in cancer cells. It is given specifically to treat metastatic breast, gastric and colorectal cancers.

To design, formulate, optimize and evaluate Capecitabine Nanosuspension using the QbD Box-Behnken model.

Deploying the Box-Behnken Design (BBD) model, Capecitabine nanosuspension was formulated with seventeen runs; the independent variables selected are Pullulan concentration, Poloxamer F407 concentration, and sonication time. The developed nanosuspension was evaluated for particle size, zeta potential, entrapment efficiency, in vitro drug release, and anti-cancer effectiveness. Drugexcipient compatibility was assessed using the Fourier transform infrared spectroscopy method. X-ray diffraction studies and differential scanning calorimetry were used to perform and assess the crystalline nature. Additionally, characteristics of the developed nanosuspension were assessed by performing a scanning electron microscopy study.

The effect of various factors on key responses, namely particle size, entrapment efficiency, and drug release up to 8 hours, was assessed. A polynomial equation was employed through the analysis 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 (85.90, 69.57, and 76.34 for particle size, entrapment efficiency, and percentage drug release at 8 hours, respectively), indicating the model's suitability. The prepared nanosuspension exhibited compatibility with the used excipients, with capecitabine-entrapped nanoparticles uniformly dispersed within the suspending medium.

Developed capecitabine nanosuspension demonstrated better efficacy and effectiveness against gastric cancer, with independent variables like pullulan and poloxamer F207 concentration, along with sonication time, influencing particle size, entrapment efficiency, and drug release.