(159d) Development Of A Fluidized Bed Granulation Process: A Comparative Analysis With Two Different Formulations

This paper presents our efforts toward the development of a fluidized bed process for granulation. Two different pharmaceutical formulations were evaluated. The first formulation (F1) contains an ultrafine, sparingly water-soluble active pharmaceutical ingredient (API) in the presence of various excipients, while the second formulation (F2) contains two highly water-soluble APIs in the absence of any excipient except the binder. A comparative analysis will be made to elucidate the differences between the growth behaviors of the two formulations.

The most striking feature of the F1 granulation was that the growth behavior was non-monotonic, whereas that of F2 granulation was monotonic, which is the most commonly observed growth behavior in the scientific literature. API aggregates of various sizes formed during the blending-heating phases and during the initial part of spraying phase of the F1 granulation. The aggregates gradually disappeared as granulation progressed upon an increase in the air relative humidity and product bed moisture. Following the initial spray period through the end of spraying, the growth was monotonic due to the usual agglomeration mechanism. It is interesting to see a transition from initial aggregate formation, to the dispersion of weak aggregates with simultaneous formation of agglomerates. Although the mechanism of aggregate formation is not fully understood, it is proposed that tribocharging of API particles may be the origin of this behavior. It was also observed that a much lower moisture level was required for an adequately granulated product in F2 granulation compared to that required in F1 granulation. The paper demonstrates the successful application of fluid bed granulation technology to two widely different formulations.