On the Fracture of Pharmaceutical Needle-Shaped Crystals during Pressure Filtration: Case Studies and Mechanistic Understanding

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• 作者：Claire S. MacLeod ; Frans L. Muller
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：March 16, 2012
• 年：2012
• 卷：16
• 期：3
• 页码：425-434
• 全文大小：539K
• 年卷期：v.16,no.3(March 16, 2012)
• ISSN：1520-586X

文摘

Pharmaceutical compounds often crystallise as particles with high aspect ratio, typically as needle-shaped particles. These particles must be isolated from the crystallisation liquors before further secondary processing to form the drug product. A common isolation method in the fine chemical and pharmaceutical industries is pressure filtration. Previous experience has shown that, on scale-up from lab to pilot plant, the particle size distribution can change quite significantly. This has typically been associated with agitation of the filter cake. To test this assumption a number of industrial case studies were conducted. The particle size distribution of various needle-shaped particles of different pharmaceutical and model compounds have been tracked through the filtration and drying process. The work here shows that, for the needle-shaped particles tested, particle breakage occurs during both pressure filtration and agitated drying. This is a previously unreported observation and is contrary to the previously held assumption that breakage is only observed during agitated drying. A mechanistic understanding of the breakage has been built up using particle dimensions, applied pressure, and bed density. The estimated stresses on the needle-shaped particles are of the same order of magnitude as typical tensile strengths of pharmaceutical materials, thus explaining why breakage is observed. A small-scale test has been developed to help identify potentially fragile compounds where breakage during pressure filtration is likely.