Advanced Powder Technology, Vol.22, No.2, 245-252, 2011
Evaluation of the influence of granulation processing parameters on the granule properties and dissolution characteristics of a modified release drug
Understanding the relationship between high shear wet granulation processing parameters and the characteristics of intermediate and final products is crucial in the ability to apply quality by design (QbD) and process analytical technologies (PAT) to secondary pharmaceutical processes. This research examined a high shear wet granulation process and subsequent manufacturing of a tablet containing a biopharmaceutics classification system (BCS) class II drug, gliclazide (low solubility, high permeability). Previous studies have concentrated on either granulation or tabletting but not both together; this work brings together the analysis as a single large multivariate process. The design of experiment (DoE) was performed according to an L9 Taguchi method with three replications, in total; thirty-six runs were performed. A full statistical analysis relating both granule and tablet properties to selected process parameters were carried out. The research illustrates that mapping a highly multivariate process is possible. Statistically significant critical process parameters were identified for granule hardness, granule density and granule particle size. These granule properties were also identified as contributing to the dissolution release characteristics. Dissolution modeling and prediction was achieved within the DoE structure. Process noise was identified and measured across the entire production and specifically with respect to the milling process. (C) 2011 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.