Application of the Modified Tangential Spray-Fluidized Bed to Produce Nonpareils from Primary Crystals.

Abstract

Coating of fine primary drug particles by a fluidized bed processor has been reported to be potentially challenging. This work aimed to develop a spray layering process to produce nonpareils by a side spray fluid bed with swirling air flow. The first part examined the effects of various parameters for producing lactose nonpareils by using Box-Behnken design. The factors considered were atomizing air pressure, spray rate, and fluidizing air temperature. This was followed by an in-depth investigation on the effects of inlet airflow rate, air temperature, and spray rate on properties of the product, in addition to process optimization. The results indicated a negative correlation between atomizing air pressure and D90 (particle size at 90th percentile in the cumulative undersize plot) as well as span (size distribution). Temperature had a positive correlation with D90 and span while spray rate affected span. Both atomizing air pressure and temperature correlated negatively with span. It was also found that spray rate negatively affected roundness at different coat weight gain levels across the study design space. Inlet airflow rate was found to correlate negatively with roundness at 15%, w/w coat weight gain. The mean useful yield of the optimized runs was about 91%. In the second part of this study, the metformin hydrochloride crystals as starter seeds were converted into nearly spherical shaped spheroids with 1:1 crystals to coat weight deposition over a processing time of about 3.5h. The processor studied shows promise for direct spheronization of crystals into spherical seeds.