Quality by Design (QbD) Approach for Optimization and Characterization of Micro emulsion based Nasal formulation of Antipsychotic/Antischizophrenic Drug- Aripiprazole

Introduction: Present study is focused to develop micro emulsion based nasal formulation of poorly water soluble antipsychotic/anti-schizophrenic drug Aripiprazole. Materials and Methods: Different surfactants and co surfactants are screened by implementing pseudo ternary phase diagram. Effect of concentrations of four independent variables- oil (X1), Surfactant (X2), co-surfactant (X3) and water (X4) on two dependent variables- particle size (Y1) and drug content (Y2) is studied from surface response plots obtained by application of Box Behnken Design Experiment. QTPP and CQA mediated risk assessment applied to ensure desirable quality, safety and efficacy of developed microemulsion. Developed microemulsion evaluated for appearance, particle size, viscosity, drug content, pH, conductivity, drug release, zeta potential, polydispersity index, nasal toxicity and stability. Results: DoE based QBD approach lead development of suitable optimized batch of Aripiprazole micro emulsion with particle size 95.2 nm, viscosity 120 cp, pH 6.0, 90%, drug content and about 87.33% nasal permeability release within 4 hr. Risk assessment helped in identifying identification robust design parameters for rapid development of stable aripiprazole micro emulsion. The critical quality attributes (CQAs) like solubility and compatibility with excipients, dosage form, particle size, turbidity, drug content and drug release have greater impact on the stability and therapeutic performance of micro emulsion of aripiprazole. Conclusion: Aripiprazole containing intranasal micro emulsion is successfully developed by quality by design approach for understanding the critical quality attributes and microemulsion is better alternative over conventional delivery systems.