Pharmaceutical Technology - October 2021


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Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 29 term storage under stress, for example, under their own weight in a hopper or storage vessel. Such compressibility can also indicate a potential for difficulty in feeding or tableting operations. Permeability values quantify a powder's ability to transmit air and are determined from measure- ments of pressure drop across a powder bed at a constant, defined air f low rate. Sample 5 gener- ates the highest pressure drop, indicating that it is the least permeable sample. Like compressibility, permeability is often linked with cohesion in the powder bed, with more cohesive powders exert- ing greater resistance to air f low. Powders with low permeability do not release air easily and this can be problematic in processes such as die fill- ing and tableting. Complete, uniform die-filling relies on the powder settling to form a uniform, efficiently packed dose; tablets containing air are more likely to be physically unstable and prone to capping. More generally, low permeability can also adversely impact gravitational f low (4). Shear stress, a shear property, was also mea- sured in this study, but the results provided no differentiation, exhibiting a %RSD of ~6% across all five materials. Shear cell analysis is a valu- able technique for assessing the ease with which a powder transitions from the static to dynamic state following consolidation, and the data sug- gest that in such circumstances, the powders may behave comparably. Set against this result are the dynamic and bulk property data that suggest the powders may behave differently. In reality, the rel- evance of different properties varies from process to process, highlighting the importance of testing powders under relevant conditions and identify- ing which properties are most applicable. Sensi- tive, multi-faceted powder testing maximizes the likelihood of detecting differences, thereby maxi- mizing a manufacturer's ability to judge whether supplies are equally acceptable. Looking ahead New pressures on supply chain management in- tensify requirements for robust specifications for products and raw materials. Identifying the prop- erties that define the in-process performance of raw ingredients and feedstocks, and their com- patibility with different equipment, is critical for manufacturers. Powders can be particularly challenging in this regard, with specifications routinely failing to detect a material that goes on to exhibit poor performance. The data presented here illustrate how advanced powder testing based on the measurement of dy- namic, shear, and bulk properties, can sensitively differentiate materials that are notionally com- parable, helping manufacturers to make a smart, informed choice of supplier. Armed with a clear understanding of exactly what constitutes an ac- ceptable supply, manufacturers are in a better position to build a supply network that answers to economic constraints while simultaneously meeting evolving needs. Such understanding also provides a secure foundation for the adaptation of existing processes to deliver new drugs, in response to disrupted supply chains or grow- ing demand. References 1. R. Mullin, Chem. Eng. News, 98 (16) 30 (2020). 2. B. Van Snick, et al., Int. J. Pharm., 549 (1–2) 415–435 (2018). 3. M.S. Escotet-Espinoza, et al., Powder Technol., 339, 659–676 (2018). 4. J. Clayton, Org. Process Res. Dev., 19 (1) 102–109 (2015). 5. J. Clayton and T. Mollner, "Integrating Powder Characteriza- tion into Raw Material Selection and Process Optimization,", Article (Oct. 1, 2019). 6. R. Freeman, Powder Technology, 174 (1) 25-33 (2007). PT

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