(431c) Modeling of Granule Size Distribution in Pharmaceutical Roller Compaction Process | AIChE

(431c) Modeling of Granule Size Distribution in Pharmaceutical Roller Compaction Process


Bobba, V., Brystol-Myers Squibb
Malladi, J., Brystol-Myers Squibb
Akseli, I., Celgene
Pharmaceutical roller compaction (RC) is a particle size enlargement process in which granules are produced by making ribbons from an active or placebo compound and milling them into smaller agglomerates. Determination of the granule size distribution (GSD) as the major product attribute requires extensive experimental efforts which are time consuming and material demanding. Modeling the impacts of process parameters and ribbon properties on granule attributes provides a quantitative insight into the RC granulation process. In this talk, we present a computational approach to simulate the size distribution of granules produced in the milling step of pharmaceutical roller compactors. RC process was emulated by making slugs and milling them with a lab hand-mill apparatus. The model was structured based on the GSD data obtained from different active compounds of Aspirin and Ibuprofen with various drug loads, including two commonly used excipients of Microcrystalline Cellulose PH102 and Lactose FastFlo 316. Experimental data were simulated using a Guassian distribution function, and the determined model parameters were correlated to ribbon Young’s Modulus. Model was validated by data which were excluded from the training set. Results demonstrated the success of the model in predicting the GSD obtained from experimental measurements. This model holds only two fitting parameters which can be determined from regular material profiling techniques. This approach can be integrated with an RC model that can predict the ribbon attributes, and be utilized as a powerful computational tool for RC process space design.