Context and objective: The objective of the study was to develop a stable capsule formulation of ziprasidone hydrochloride which can be administered without regards to food intake.
Materials and methods: The unstable anhydrous form of ziprasidone hydrochloride was stabilized employing hot-melt extrusion and further optimized by 32 central composite design. The formulation was optimized after establishing acceptable ranges for response variables like disintegration time, dissolution and impurity profile. A crossover fasted and fed in vivo study was conducted in human volunteers to assess the food-effect of optimized formulation vis-à-vis the marketed brand.
Results and discussion: The optimized formulation met in-house specifications for various response variables. Further, high values of correlation coefficient vouch the adequate selection of experimental design and its high prognostic ability. In our study, no significant difference was observed between the Cmax and AUC values after administration of the optimized formulation in fasted and fed states. On the contrary, there was a statistically significant increase in the Cmax and AUC values after oral administration of Zeldox in fed state in comparison to fasted state.
Conclusions: The present study describes the successful development of a stable formulation of 20 mg of ziprasidone devoid of any food-effects.
Keywords: Central composite design; XRD; food-effect; hot-melt; pharmacokinetics.