SimCU: A new model to assess content uniformity of oral dosages based on particulate mass balances and Monte Carlo simulations

Abstract A new model (SimCU) is presented to assess the risk of failure on content uniformity for oral dosage forms. The proposed model is an extension to the algorithm presented by Zhang and Johnson (Int. J. Pharm. 1997;154:179–183), including a revision needed to prevent artificial loss of drug and segregation. Furthermore, the improved approach is extended to enable the user to consider alternate sources of variability such as the weight distribution of the dosage forms and the effect of a drug product intermediate (i.e., a granule) with heterogeneous potency levels across particle sizes. The particle mass balance in the corrected algorithm is consistent and its closed form solution for the prediction of the relative standard deviation of potency is presented herein. Predictions of the relative standard deviation (RSD) from SimCU were extensively verified with data from development, clinical and commercial manufacture. Such results support the usage of the proposed model to assess the risk of failure for content uniformity for oral dosage forms which will ultimately drive the specifications for particle size distribution of the drug.