The purpose of this work was to develop a methodology that quantifies the extent of shear induced during an encapsulation process and show how formulation composition and manufacturing process designs can be changed to reduce the negative impact on drug product quality attributes. The powder feed system used in a dosing disc type pharmaceutical capsule filling machine induced additional shear of the powder prior to slug formation. The shear occurred both in the hopper portion, via the rotation of the feed auger and impeller, and in the powder bowl via the tamping pin agitation and/or shear against the stationary surfaces such as the powder level scraper. The extent of shear was quantified to assess the impact of further dispersing the hydrophobic lubricant, magnesium stearate, in both active and placebo formulations. Stratified samples over the course of the encapsulation run showed suppression in the drug dissolution profiles and decrease in the interparticulate tensile strength of the encapsulated product. The amount of shear (duration and rate) induced during the encapsulation unit operation can be much greater than that from typical bin blending operations and therefore requires consideration during product design and scale-up to ensure product robustness.
Keywords: Capsule; dissolution; encapsulator; lubrication; shear; tensile strength.