Novel powder property-based indices for predicting segregation risk in multicomponent pharmaceutical blends

Area of Science:

• Pharmaceutical Manufacturing
• Materials Science
• Chemical Engineering

Background:

• Powder segregation is a major challenge in pharmaceutical production, impacting drug product quality due to uneven active ingredient distribution.
• Understanding segregation drivers is crucial for developing stable and effective drug formulations.

Purpose of the Study:

• To evaluate powder segregation behavior in pharmaceutical blends with varying active pharmaceutical ingredients (APIs), excipients, drug loadings, and ratios.
• To develop and validate predictive indices for assessing segregation risk in early-stage formulation development.

Main Methods:

• Utilized Near-Infrared (NIR) spectroscopy for content analysis of model APIs (acetaminophen, ibuprofen sodium).
• Employed a modified Jenike and Johanson tester to assess powder blend segregation propensity.
• Performed statistical analysis to identify critical formulation variables and their interactions.

Main Results:

• Significant interactions between formulation variables (drug loading, excipient ratios) were identified.
• Particle size distribution and flow characteristics were critical factors influencing segregation.
• Developed a modified segregation index and two composite parameter indices, validated with commercial blends, showing improved correlation with material properties.

Conclusions:

• Identified key parameters (D50, D90/D10, flowability, size distribution width) predicting segregation risk.
• The developed composite indices offer a practical tool for rapid segregation risk assessment in early formulation development.
• This approach facilitates the creation of robust pharmaceutical formulations with minimized segregation risk.