Optimization of the experimental parameters of fluticasone propionate microparticles for pulmonary delivery using a box behenken design.

The objective of this study was to examine extensively the influences of formulation and process variables on the microparticles. The microparticles were generated by the spray-drying technique using polymer chitosan, mannitol along with L-leucine. The effects of various experimental parameters such as polymer concentration, inlet temperature, and feed flow rate on particle size and production yields were evaluated by means of experimental box-behnken design. Multiple regression analysis was carried out and response surfaces were obtained. Optimized formulation and check points batches were selected by feasibility and grid search. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the production yield. Feed flow rate impact on particle size. Results showed that spray drying technique yield 985 to 4060 nm indicate micro size range and production yield was found in between 27.01-52.96%. The selection of appropriate parameters yielded spray-dried microparticles characterized by narrow dimensional distribution. In our present work, prepared microparticles using the spray-drying technique and systematically estimated their feasibility for the pulmonary delivery of microparticles by careful investigations of their characteristics and aerosolization properties. Spray drying technique yield optimum size for deposition beyond the narrow airway into the alveoli and suitable for respiratory deposition.

Drug targeting to pulmonary are effective if given in uniform quantity, deposit in the appropriate lung region and appropriate particle size. The broadest and deepest penetration of particles into the airways and their deposition in the deep parts of the lung such as alveoli are achieved when the particle size range between 1 and 5 μm. The microparticles may be promising vehicles of transporting drugs effectively to the epithelium while avoiding unwanted mucociliary clearance, hence the properties of microparticles may be utilized for therapeutic treatments of lung specific diseases they can reach the lungs. Spray drying is well-established drying process the microencapsulation of drugs due to reliability, reproducibility and possible control of particle size and drug release. In addition, it has the advantage of being a continuous process which is easy to scale-up and microparticles obtained by spray-drying are usually free of organic solvents.

Subjects and Methods

Fluticasone propionatemicroparticles were prepared by the spray-drying method using chitosan, mannitol along with L-leucine. Optimizing of spray drying parameters was done by box behnken design. The box-behenken design was used in the study. The independent and dependent variables are listed in Table 1 throughout the study. 15 batches were prepared.

Table 1

Variables and their levels in box-behnken design

Results and Discussion

The mean particle size of microparticles was ranged between 985-4090 nm. The particle sizes of the microparticles were increased with the increase in the chitosan concentration. As low polymer concentration decreases the amount of solid in each droplet exiting the nozzle. Inlet temperatures of air-drying and feed flow rate are important parameters for particle size. A curvilinear relationship was observed between feed flow rate and particle size. Production yield was found to be affected by changing the spray drying conditions like inlet temperature and feed flow rate as well as concentration of polymer. The production yield was found in between 27.01-52.96%. This difference may be attributed to either higher temperature or higher polymer concentration. Inlet temperatures of air-drying and polymer concentration are important parameters for production yield. A linear relationship was observed between polymer concentration, inlet temperature and production yield.

Conclusion

The present work mainly emphasis on the effect of polymer and instrumental variables on particle size and yield of the product. This delivery platform opens up a wide range of treatment applications of pulmonary disease via microparticles.