A Simplex Centroid Design to Quantify Triboelectric Charging in Pharmaceutical Mixtures

Area of Science:

• Pharmaceutical Science
• Materials Science
• Statistical Modeling

Background:

• Triboelectrification, or charge transfer, is a critical phenomenon in pharmaceutical powder handling and processing.
• Understanding charge generation in drug-excipient mixtures is essential for preventing processing issues and ensuring product quality.
• Previous studies have not fully elucidated the complex interactions governing triboelectrification in multi-component pharmaceutical systems.

Purpose of the Study:

• To investigate and predict the triboelectrification phenomenon in pharmaceutical mixtures using a modified simplex centroid design.
• To identify the key factors influencing charge transfer, including drug type, excipient type, and blender wall material.
• To analyze excipient-drug interactions and their impact on charging behavior in binary and ternary pharmaceutical blends.

Main Methods:

• Application of a modified simplex centroid statistical design for predicting triboelectrification.
• Systematic study of two drugs (Ibuprofen, Theophylline), two excipients (lactose monohydrate, microcrystalline cellulose/MCC), and two blender wall materials (aluminum, poly-methyl methacrylate).
• Analysis of charge transfer trends and component ratio effects on bulk charging.

Main Results:

• Excipient-drug interactions were identified as the most significant factor reducing charging, regardless of blender wall material.
• Lactose monohydrate provided more consistent explanation of charge variability than microcrystalline cellulose when used as a secondary excipient.
• The ratio of individual components explained a substantial portion of bulk charging: ~80% for Ibuprofen and ~70% for Theophylline mixtures.
• Ternary systems containing both lactose and MCC showed potential reduced efficacy compared to binary mixtures in impacting charge variability.

Conclusions:

• Excipient-drug interactions are paramount in controlling triboelectrification in pharmaceutical blends.
• The composition ratio of blend components is a strong predictor of charge transfer.
• Lactose monohydrate demonstrates more predictable behavior in influencing charge variability compared to MCC in these systems.