A concept to predict particle segregation problems in pharmaceutical gravity discharge processes

Tablets continue to be the predominant dosage form of drugs in the pharmaceutical industry, yet their manufacture is frequently plagued by out of specification product. It happens that some drug powders tend to segregate prior to tableting and that determination is only made at a process validation stage. By then if modifications to the handling equipment are needed they are often not economical should the process require revalidation. Instead manufacturers will opt to routinely discard those parts of the batch which are found to be afflicted. This paper suggests a way to predict segregation problems ahead of process validation, and therefore avoid such measures. As powder is discharged onto a tableting press, usually by free fall through a vertical chute, segregation can occur because different particles will experience different settling velocities. Here that phenomenon is treated as a 'weakness' in the material interacting with a 'harshness' of the process geometry. A matrix based analysis is presented as a means to decouple one from the other. Experimental verification of this is the subject of on-going work. It is hoped the effect of the process may then be captured by pilot scale trials of a reference material, whilst a bench scale test suffices to determine the effect of the material. Each effect is thus independently determined, so that superposing the two enables a qualitative prediction of segregation tendency. Initial findings from the bench scale tests are reported, where by subjecting small amounts of material to counter current airflows, the responses of some common pharmaceutical excipients are compared. It is also demonstrated how these findings may be quantified by particle size analysis, using laser diffraction and a carefully selected sampling technique.