Evaluation of models for predicting spray mist diameter for scaling-up of the fluidized bed granulation process.

We evaluated models for predicting spray mist diameter suitable for scaling-up the fluidized bed granulation process. By precise selection of experimental conditions, we were able to identify a suitable prediction model that considers changes in binder solution, nozzle dimension, and spray conditions. We used hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or polyvinylpyrrolidone (PVP) binder solutions, which are commonly employed by the pharmaceutical industry. Nozzle dimension and spray conditions for oral dosing were carefully selected to reflect manufacturing and small (1/10) scale process conditions. We were able to demonstrate that the prediction model proposed by Mulhem optimally estimated spray mist diameter when each coefficient was modified. Moreover, we developed a simple scale-up rule to produce the same spray mist diameter at different process scales. We confirmed that the Rosin-Rammler distribution could be applied to this process, and that its distribution coefficient was 1.43-1.72 regardless of binder solution, spray condition, or nozzle dimension.