Elucidating critical factors driving the tabletability flip phenomenon

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Tabletability, crucial for tablet formation, depends on interparticulate bonding area (BA) and bonding strength (BS).
• The tabletability flip phenomenon (TFP) describes a decrease in a drug's tabletability when formulated with excipients compared to its pure form.
• Factors influencing BA and BS, such as mechanical properties and particle characteristics, can affect TFP, but systematic evaluation is lacking.

Purpose of the Study:

• To systematically evaluate the impact of API loading, excipient type, particle size, and tableting speed on TFP.
• To identify key formulation and processing parameters that influence the occurrence and extent of TFP.

Main Methods:

• Investigated TFP by varying API loading, excipient type, particle size (API and excipient), and tableting speed.
• Analyzed the relationship between these parameters and the observed tablet tensile strength and tabletability.

Main Results:

• TFP is more likely when excipient plasticity matches the softer API, particularly at intermediate drug loadings and high compaction pressures.
• Excipient particle size significantly impacts both the occurrence and extent of TFP.
• API particle size and tableting speed showed only marginal effects on TFP.

Conclusions:

• Excipient plasticity and particle size are critical factors in managing TFP.
• Formulation strategies should consider the interplay between API and excipient mechanical properties and particle characteristics to mitigate TFP.
• Optimizing tableting conditions, particularly excipient selection and particle size, is essential for predictable tabletability.