Formulation and evaluation of Rifampicin loaded poly-ε-caprolactone nanoparticles using 3^2 factorial design

Abstract

The objective of this work was to apply the response surface approach in the development of Rifampicin nanoparticle with poly-ε-caprolactone (PCL). Experiments were performed according to a 3² factorial design to evaluate the effects of two independent variables, Sonication time (X₁) and PCL amount (X₂) on the percent entrapment efficiency (% EE), mean diameter (MD) of the Rifampicin nanoparticle. The effect of the two independent variables on the response variables was studied by response surface plots and contour plots generated by the Design Expert® software. The compatibility between Rifampicin and the other excipients were confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) studies. The sonication time has an antagonistic effect on % EE and Mean diameter of the nanoparticle but the effect of polymer amount was synergistic one. A nonlinear twisted relationship was obtained for both EE and MD, which indicated an interaction between them at the corresponding factor levels. Kinetic treatment to the dissolution profiles revealed that the drug release follows Highuchi equation which confirms the burst release pattern. The desirability function was used to optimize the response variables, and the observed responses were in agreement with the experimental values. These results indicate that Rifampicin loaded PCL nanoparticles could be effective in sustaining its release for a prolonged period. The PCL NPs could be alternate method for delivery for Rifampicin with prolonged drug release profiles and better therapeutic effect can be achieved for the treatment of tuberculosis. However, further studies are needed to confirm its performance in vivo.