Particle Size Limits to Pass the Acceptance Value (AV)-Based USP Content Uniformity Test for Tablets

Area of Science:

• Pharmaceutical Sciences
• Drug Manufacturing
• Physical Pharmacy

Background:

• Previous methods correlated particle size and distribution with United States Pharmacopeia (USP) content uniformity (CU) test success.
• These methods were based on older USP CU test criteria.
• The current USP/NF standards (e.g., USP42/NF37) utilize a new Acceptance Value (AV)-based CU criterion.

Purpose of the Study:

• To develop a new method for calculating the maximum particle size limit for passing the AV-based CU test.
• To ensure a specified probability (e.g., 99%) of passing the updated USP CU test.
• To provide guidance for setting particle size specifications, particularly for low-dose drugs.

Main Methods:

• Utilized the same assumptions and conditions as prior work by Yalkowsky et al. and Rohrs et al.
• Developed a novel calculation to determine the upper particle size limit.
• Focused on ensuring compliance with the AV-based CU criterion at a defined probability.

Main Results:

• Identified a maximum particle size limit necessary for passing the AV-based CU test.
• Found that the required particle size is similar but slightly smaller compared to the previous USP CU test (e.g., USP28/NF23).
• Demonstrated the impact of the updated CU criterion on particle size specifications.

Conclusions:

• The updated AV-based USP CU criterion necessitates adjustments in particle size specifications.
• The new method provides a reliable way to determine particle size limits for modern drug formulations.
• Slightly smaller particle sizes are generally required to meet the current content uniformity standards.