[learn_more caption=”William R. Ketterhagen”] William R. Ketterhagen, Drug Product Design, Process Modeling & Engineering Technology,

Pfizer Worldwide Research and Development, Groton, CT[/learn_more]

Abstract:

Lubricants such as magnesium stearate are typically added to the powder blend or granulation in the manufacture of pharmaceutical tablets and capsules in order to reduce the friction between the powder and the tablet press or encapsulator components. The presence of the lubricant is generally necessary to improve manufacturability of the dosage form, but if the lubricated blend is exposed to excessive shear strain during processing prior to tableting or encapsulation, the lubricant can become too highly dispersed, resulting in adverse effects on quality attributes of the final dosage form. These effects can include an increase in wetting contact angle, a slowdown in disintegration and dissolution, and a reduction in tensile strength.

In this work, two different modeling approaches are described to quantitatively predict the extent of lubrication in a powder feed system and the resulting impact on quality attributes of interest. In the first approach, a framework using the discrete element method (DEM) is described where a companion study in a lab-scale, high-shear mixer is used to map the extent of lubrication predicted in the DEM model to an experimentally relevant tensile strength prediction. In a second modeling approach, a compartment modeling approach is developed to model the powder flow pattern and predict the lubrication-based tensile strength reduction. Parameter estimation is conducted through the use of a separate experiment utilizing an input step change in powder feed from undyed to dyed material. The tensile strength predictions from each of these modeling approaches are compared to experimental tensile strength data determined by compaction simulation of stratified samples from batch manufacture.