Formulation optimization of controlled release diclofenac sodium microspheres using factorial design

Abstract

Diclofenac sodium is an ideal candidate for incorporation in a controlled release device to diminish its adverse effects after oral administration. Microspheres were prepared by using sodium alginate as a polymer and CaCl 2 as a cross-linking agent. In this investigation, 3 3 full factorial design was used to investigate the joint influence of three variables: the stirring speed ( X 1), concentration of CaCl 2 ( X 2) and % of heavy liquid paraffin in a blend of heavy and light liquid paraffin in the dispersion medium ( X 3) on the time for 80% drug dissolution ( t 80). Potential variables such as concentration of sodium alginate and drug: sodium alginate ratio were kept constant in the experimental design. A statistical model with significant interaction terms is derived to predict t 80. The results of multiple linear regression analysis and F-statistics revealed that for obtaining controlled drug release, the microspheres should be prepared using relatively lower stirring speed, higher concentration of CaCl 2 and higher percentage of heavy liquid paraffin in the dispersion medium. The X 1 X 2 and X 2 X 3 interactions were found to be statistically significant in nature. A response surface plot is presented to show the effects of X 1, X 2 and X 3 on t 80. The drug was released by diffusion of anomalous type. A model was validated for accurate prediction of drug release profile. Acceptable batches were identified in the experimental design with constraints on percentage drug released in 1, 6 and 8 h.