Application of classical experimental design for the development of theophylline microspheres

Microspheres of theophylline were prepared by ionotropic gelation method. The objective of this study was to investigate the influence of variables such as stirring speed, concentration of CaCl2 and composition of the dispersion medium on the characteristics of the microspheres. A 3(3) randomized full factorial design was used to study the effect of the selected variables on the time for 90% drug dissolution (t(90)). A linear model with interactive terms was generated using the multiple linear regression approach. F-statistics was carried out to evolve the reduced model. Significant interactions were not detected between the selected variables. Good agreement was observed between the predicted and experimental check-point. The microspheres were evaluated for in vivo studies in dogs and the pharmacokinetic parameters were estimated by performing non-linear regression analysis. The Wagner-Nelson method was adopted to compute the percentage drug absorbed. A good correlation was observed between the in vitro and in vivo results.