A qualitative method for monitoring of nucleation and granule growth in fluid bed wet granulation by reflectance near-infrared spectroscopy.

Potency and content uniformity of granulation and tablet samples are usually determined by HPLC or UV-VIS. However, these methods are not suitable for the determinations of other important process related attributes. The monitoring of nucleation, granule growth and granule breakage in the granulation process requires different analytical tools. In early formulation development of a new active pharmaceutical ingredient (API), out of trend content uniformity results were observed for batches manufactured using a fluid bed wet granulation process. A qualitative near infrared (NIR) method was used to characterize the process samples, which were separated into fractions with sieve sizes of 40, 60, 80, 100, and 200-mesh. Based on spectral analysis, the method was able to demonstrate changes in relative content of lactose, microcrystalline cellulose and the API at different processing times. The results also showed that the out of trend content uniformity was caused by large particle size of the API. Because lactose and microcrystalline cellulose are commonly used ingredients in wet granulation formulations, the qualitative NIR method may find wide applications.