Formulation optimization of long-acting depot injection of aripiprazole by using D-optimal mixture design.

Non-adherence to medication specifications is a major cause for poor outcomes in the therapy of schizophrenia. In situ implantable preparation of aripiprazole, an atypical antipsychotic drug, was intended with the aim to improve the patient compliance and to offer an effective antipsychotic drug therapy. D-optimal mixture design was employed to design and optimize long-acting depot injection of aripiprazole using polylactide-co-glycolide (PLGA) 50:50, 75:25, 85:15, and cholesterol as release rate-retarding material. Desirability technique was used for the optimization of formulation. Predicted optimized formulation was experimentally validated, and it was found that the developed formulation releases the drug for a 14-day time period. The optimized formulation showed that the cholesterol-containing formulation exhibits a better drug release profile. The pharmacokinetic studies confirmed that the developed cholesterol-based depot formulation was capable of releasing the drug for a time period of more than 14 days. The implant formulation was sterilized by gamma radiation and ethylene oxide sterilization method. The D-optimal mixture design was proved to be an efficient technique for the formulation optimization.

D-optimal designing and optimization of long acting microsphere-based injectable formulation of aripiprazole.

This work was aimed to design and optimize a long acting microsphere-based injectable formulation of aripiprazole by using D-optimal experimental design methodology. Microspheres were prepared by solvent evaporation method using PLGA and cholesterol as release rate retardant materials. The microspheres were characterized for their encapsulation efficiency, particle size, surface morphology, residual solvent content, and drug release behavior. Contour plots were plotted to study the encapsulation and release behaviour of the drug from the microspheres. Desirability technique was used for the optimization of microsphere formulation composition. By using an optimum blend of drug and cholesterol in the microsphere formulation it was possible to attain a consistent drug release for a period of 14 days. The results have confirmed that the D-optimal experimental design technique can be successfully employed for designing the long acting microsphere dosage form.