Material-Sparing Approach to Predict Tablet Capping Under Processing Compression Conditions Based on Mechanical and...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Tablet capping is a critical manufacturing defect affecting drug product quality.
• Traditional methods for assessing capping risk are material-intensive and time-consuming.
• Predictive modeling offers a potential material-sparing alternative for process optimization.

Purpose of the Study:

• To evaluate the efficacy of compaction simulation-based mechanical models for predicting tablet capping.
• To establish material-sparing methods for determining threshold compression pressures (TCP) for Acetaminophen (APAP) and Ibuprofen (IBU).
• To validate predictive models using molecular simulations and X-ray powder diffraction (XRPD).

Main Methods:

• Mechanical properties of APAP and IBU formulations were measured and analyzed using Principal Component Analysis (PCA) and Principal Component Regression (PCR).
• PCR models predicted capping scores (CS) based on compression pressure (CP).
• Molecular models, incorporating XRPD data, calculated slip plane properties to predict TCP and validate mechanical model predictions.

Main Results:

• APAP formulations showed a quadratic relationship between CS and CP, with a TCP between 200-300 MPa.
• IBU formulations exhibited a linear relationship between CS and CP, with a TCP between 100-200 MPa.
• Mechanical and molecular models accurately predicted TCP values (245 MPa for APAP, 175 MPa for IBU), aligning with observed capping behavior.

Conclusions:

• Compaction simulation-based mechanical models are effective, rapid, and accurate tools for predicting tablet capping risk.
• These models serve as a valuable material-sparing approach for pharmaceutical process development and optimization.
• Understanding the relationship between compression pressure, material properties, and molecular behavior is key to preventing tablet capping defects.