Edward Yost, Genentech
Physical tablet defects are related to internal structural defects that are not easily assessed by the traditional methods – such as dusting, laminating, or fracturing during appearance, friability, or hardness testing. Also, these methods do not allow objective and quantitative investigation of the role of formulation and process variables, which is essential for quality-by-design (QbD) drug product development. Increased understanding of tableting risks is essential to identify the relative impact of formulation and process changes on product quality. Therefore, an x-ray microcomputed tomography (XμCT) method to analyze internal tablet defects was developed using tablets from a QbD design-of-experiment (DoE) study. Average contiguous void volume by optical image processing and artificial intelligence-based image processing to determine fracture size distribution and direction quantified the internal tablet fracture severity.
XμCT increases formulation and process knowledge in support of scaleup manufacturing. Thus, it can be incorporated as a part of a holistic approach to quantitatively identify and mechanistically assess the risks of internal tablet defects. Furthermore, expanding the use of XμCT with an artificial intelligence-based quantitative analysis can deepen our tableting knowledge from an empirical understanding to a mechanistic understanding of compaction phenomenon.
Edward Yost
Ed is a Sr. Scientific Researcher in the small molecule pharmaceutics group at Genentech. He has 18 years of small molecule formulation development experience – injectable, meter dose inhaler, dry powder inhaler, and immediate release tablet dosage forms – from pre-clinical to late-stage development. During the past 11 years at Genentech, he has developed dry powder inhaler and tablet formulations while implementing mechanical property and process simulation assessment strategies. Ed is the current chair of the AAPS Bay Area Discussion Group, and his research interests include process simulation for material-sparing tablet development and particle dispersion for inhalation delivery.