Formulation Optimization of Intranasal Spray- Dried Mucoadhesive Microparticles of Felodipine Using Experimental Design

Abstract

Spray drying technique for formulation of microparticles compared to conventional methods is proved successful in pharmaceutical research due to unique features of rapid process, reproducibility, comfortable scale up and desired end product properties. Felodipine, a 1,4-dihydropyridine-derivative calcium channel blocking agent, used widely for the treatment of hypertension, was taken as model drug. Effect of polymeric concentration, drying chamber temperature, feed rate of slurry into drying chamber and aspiration rate were studied for felodipine loaded chitosan microparticles. Plackett- Burman design was used to screen the critical process parameters influencing the percent yield, entrapment efficiency, particle size (d50), flow property, drug release in 60 min (t60) and 480 min (t480) of the microparticles. The seven factors studied were feed rate, temperature, aspiration, water : ethanol ratio, amount of polymer, amount of mannitol and amount of propylene glycol. The study revealed that the temperature, aspiration and amount of polymer significantly influenced the experimental responses; while feed rate, water:ethanol ratio, amount of mannitol and amount of propylene glycol had negligible effect on the spray drying process. Hence, these process parameters were further optimized by applying Central Composite Design with 15 batches consisting of 23 factorial points, six axial points and one batch at the center of domain. Results of central composite design batches revealed that significant difference was not found in entrapment efficiency and t480 among all the batches, hence, further optimized batches were formulated based on desired value for the % yield, flow property and t60. Three different batches for optimization were formulated from the overlay contour plot developed using Design Expert® software for the desired region of selected responses. Further evaluations like SEM, FT-IR, DSC, Mucoadhesion and in-vitro diffusion study for optimized batch were carried out. The optimized batch was shown good entrapment of drug in polymeric matrix, acceptable mucoadhesion and diffusion characteristics. Further scale up and pharmacokinetic study is required before its take formulation to the market.