Quantifying and reducing powder shear sensitivity when manufacturing capsules with lubricants.

Area of Science:

• Pharmaceutical Manufacturing
• Drug Product Quality
• Process Engineering

Background:

• Pharmaceutical capsule filling involves powder handling processes that can induce shear.
• The extent and impact of shear on drug product quality attributes are not fully understood.
• Magnesium stearate, a common hydrophobic lubricant, can be affected by shear, influencing powder properties.

Purpose of the Study:

• To develop a quantitative methodology for assessing shear during pharmaceutical encapsulation.
• To investigate how formulation composition and manufacturing process design influence shear-induced effects.
• To identify strategies for reducing the negative impact of shear on drug product quality.

Main Methods:

• Quantification of shear forces within a dosing disc capsule filling machine.
• Analysis of powder feed systems, including auger, impeller, and tamping pin actions.
• Assessment of shear impact on magnesium stearate dispersion in active and placebo formulations.
• Evaluation of drug dissolution profiles and interparticulate tensile strength of encapsulated products.

Main Results:

• The powder feed system in capsule filling machines induces significant shear prior to slug formation.
• Increased shear led to suppressed drug dissolution profiles.
• Shear resulted in a decrease in the interparticulate tensile strength of the encapsulated product.
• The duration and rate of shear during encapsulation can exceed that of typical bin blending.

Conclusions:

• Shear induced during pharmaceutical capsule filling is a critical process parameter affecting drug product quality.
• Formulation composition and manufacturing process design must be optimized to minimize shear.
• Understanding and controlling shear are essential for ensuring product robustness during development and scale-up.