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

Abstract

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 variablesparticle 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.

Quality by design enabled self-nano emulsifying drug delivery systems development for the oral delivery of telmisartan: Improvement of biopharmaceutical performance

“…The winning recipes were put through a centrifugation procedure that lasted for thirty minutes and consisted of 3,500 revolutions per minute. In order to select the formulations to use in the freeze-thaw stress test, it was necessary to determine which ones did not display phase separation [25].…”

“…It is also utilized as a parameter in the estimation of nano-emulsion droplet size distribution, where droplet size is measured by light scattering detected at a 90º angle. The refractive index of selected formulations was measured with an Abbe refractometer that was calibrated with castor oil [25,26].…”

“…Six cycles between 4ºC and 45ºC with storage at each temperature for at least 48 h were investigated. Those formulations that were stable at these temperatures were centrifuged [24,25].…”

“…After that, a dissolving tester was placed inside of a treated dialysis bag that contained 500 liters of Nano emulsion (which is equivalent to 40 milligrams of telmisartan powder). An aliquot (0.5 ml) of the sample was taken at predetermined intervals (5,15,25,35,45,60,90, and 120 min), ltered, diluted, and then examined for the presence of telmisartan using a Shimadzu-1800 UV visible spectrophotometer at max 205 nm and 248 nm for SGF pH1.2 and pH 6.8 phosphate buffer, respectively. The results indicated that telmisartan was present in [18][19][20].…”

“…A dissolving tester was lled with Telmisartan-loaded solid SEDDS, which is comparable to 40 mg of telmisartan powder. An aliquot (0.5 ml) of the sample was taken at speci ed intervals (5,15,25,35,45,60,90, and 120 minutes), ltered, diluted, and tested for the presence of telmisartan using a Shimadzu-1800 UV visible spectrophotometer at max 205 nm and 248 nm for SGF pH 1.2 and pH 6.8 phosphate buffer, respectively [28].…”