Potential of Powder Rheology for Detecting Unforeseen Cross-Contamination of Foreign Active Pharmaceutical...

Area of Science:

• Pharmaceutical Manufacturing
• Materials Science
• Analytical Chemistry

Background:

• Cross-contamination by foreign active pharmaceutical ingredients (APIs) is a significant risk in pharmaceutical production.
• Current quality control methods, like liquid chromatography, may miss unexpected contaminants if they only test for known impurities.
• Ensuring drug safety and supply stability requires robust methods to detect foreign component presence.

Purpose of the Study:

• To evaluate the efficacy of powder rheometry in detecting the impact of foreign APIs on powder flow properties.
• To determine if powder rheometry can identify subtle changes in powder characteristics caused by unexpected contaminants.
• To assess the suitability of powder rheometry for pharmaceutical quality control to prevent cross-contamination.

Main Methods:

• Aspirin (host API) was blended with guest APIs (acetaminophen, albumin tannate) and common lubricants (magnesium stearate, leucine).
• Powder samples underwent shear and stability tests using a powder rheometer.
• Microscopic morphological analysis was performed to observe physical interactions between APIs.
• Flowability was assessed in a direct compression formulation containing guest APIs and common excipients (microcrystalline cellulose, potato starch, lactose).

Main Results:

• Powder rheometry successfully detected guest APIs in most cases, identifying variations in powder diameter, pre-milling, and cohesion.
• Microscopic analysis confirmed physical interactions between host and guest APIs.
• Even in complex formulations with multiple excipients, the presence of guest APIs was detectable.
• The method demonstrated sensitivity to changes induced by foreign APIs.

Conclusions:

• Powder rheometry is a valuable tool for detailed powder characteristic analysis in pharmaceutical quality control.
• This technique shows promise for identifying and mitigating risks associated with foreign API cross-contamination.
• Implementing powder rheometry can enhance the stability of pharmaceutical product quality and improve customer safety.