The Effect Of Shape For The Prediction Of Powder Segregation In Pharmaceutical Solid-Dosage Form Applications

Proper mixture of Solid-Dosage therapeutics is critical for many aspects of drug manufacturing as well as drug delivery.  From the very start, milled Active Pharmaceutical Ingredients (API) are mixed with excipients at a pre-determined quantity to ensure the right amount of therapeutic is delivered at the target area of the body.  However, once a mixture of these two or more ingredients are made, it is important to monitor the consistency of the mixture as the ingredients travel their way from mixing to tableting.  As with all milled materials, the flowability of smooth / round particles will vary drastically from rough / high aspect ratio particles. 

There are many types of excipients used in the pharmaceutical industry.  Excipients are selected for various properties.  How they interact with the API, how they allow the proper flow and mixture of the ingredients, and even how they impact the bio availability of the therapeutic.  From Lactose, to Titanium Dioxide, most of these excipients are far from being smooth and round.  Most in fact, are irregular.  When we look at API’s, most are created under a crystallization environment and then milled.  Milling influences crystalline particles. The result can be block-shaped particles, fine particles and even some long high-aspect ratio particles.  Blending these milled API’s with a variety of excipients presents a challenge when the assumption is made that as the blend travels toward a tableting press, the blend has not segregated.  In fact, just by the very nature of having multiple ingredients of different shapes traveling down a trough or in a pipe, the powder flow dynamics will result in a segregated mixture at the point of tableting.  Segregated Solid-Dosage mixtures can lead to inconsistent and even dangerous dosages being tableted.  Usually discovered very late in the process, the inability to monitor this consistent mixture of blended particles leads to rework and loss of time and money.  Segregation is one of the three main causes of process failure in systems that handle powder materials.