Abstract

The study was undertaken with an aim to investigate the ability of native sugars (e.g. glucose, fructose and sucrose) to induce crosslinking of gelatin for the preparation of modified release microspheres of diclofenac sodium. The microspheres were prepared by emulsion crosslinking method and they were evaluated for drug content, in vitro drug release and size analysis. The results of preliminary trials revealed that the parameters such as drug to gelatin ratio, volume of light liquid paraffin and stirring rate were found to affect the morphology and in vitro drug release, of microspheres. The microspheres crosslinked with glucose showed highest drug content, good yield and lowest burst effect. The evidence of glucose mediated crosslinking of gelatin was confirmed by DSC. A 32 fuII factorial design was adopted to investigate the joint influence of two variables, amount of glucose (X1; 1,1.5 or 2 g) and concentration of gelatin (X2; 10,15 or 20% w/v) on the percentage drug released in 60 min (Y60) and the time required for 80% drug dissolution (t80) while keeping the other variables constant. The results of multiple linear regression analysis revealed] that for obtaining modified drug release up to 12 h, the microspheres should be prepared using higher level of glucose and middle level of gelatin. Response surface plots are presented to show the effects of X1 and X2 on Y60 and t80. The drug release pattern fitted well to Korsmeyer and Peppas model indicating anomalous diffusion. An equation was generated by adopting multiple linear regression analysis, for predicting the drug dissolution profile for a check point. Good agreement was observed between the predicted and observed drug dissolution profiles. The results suggest that native glucose could be an interesting agent to crosslink gelatin for obtaining modified release of diclofenac sodium from the microspheres.