Correlation of Drug Substance Particle Size Distribution with Other Bulk Properties to Predict Critical Quality Attributes

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• 作者：Henry G. Morrison ; Wenle Tao ; William Trieu ; Shawn D. Walker ; Sheng Cui ; Seth Huggins ; Karthik Nagapudi
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：September 18, 2015
• 年：2015
• 卷：19
• 期：9
• 页码：1076-1081
• 全文大小：452K
• ISSN：1520-586X

文摘

The purpose of this study was to correlate the particle size distribution (PSD) of a development molecule (1) with other bulk properties such as surface area and powder flow, to enable prediction of critical quality attributes (CQA) of the drug substance to support a roller compaction formulation process. Dry dispersion laser diffraction, wet dispersion laser diffraction, and wet dispersion image analysis PSD methods were developed for 1. Twenty eight (28) process batches were characterized by all three methods, and the resulting data were correlated to other bulk properties to determine if these correlations could be used to predict CQA values for future process batches. PSD metrics measured with wet dispersion laser diffraction and wet dispersion image analysis methods were found to have significantly better correlation to other bulk properties when compared to the metrics measured using the dry dispersion laser diffraction method. The correlations generated were found to be useful to predict resulting surface area and flow function values during process development. On the basis of these correlations, a target PSD range was identified for 1 that could support the roller compaction process. In order to further validate this methodology, various grades of lactose monohydrate were then used as a second model system to test correlation between PSD and other bulk properties.