Flexible modelling of the dissolution performance of directly compressed tablets

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Pharmacy

Background:

• Accurate prediction of drug dissolution from directly compressed tablets is crucial for pharmaceutical development.
• Existing models may not fully capture the complex interplay between tablet disintegration and drug dissolution.
• Understanding manufacturing effects on tablet performance is essential for quality control.

Purpose of the Study:

• To propose and evaluate a novel compartmental model for predicting tablet disintegration and dissolution.
• To link raw material properties to tablet performance in directly compressed dosage forms.
• To explore the model's utility for real-time release testing in continuous manufacturing.

Main Methods:

• Development of a three-compartment model (Bound, Disintegrated, Dissolved) for active pharmaceutical ingredient particles.
• Incorporation of three fitting parameters (β₀, βt,0, α) to describe tablet disintegration dynamics.
• Integration of the Nernst-Brunner equation with hydrodynamic effects for dissolution rate calculation in a USP II apparatus.

Main Results:

• The model successfully describes the disintegration and dissolution performance of directly compressed tablets.
• Key model parameters show strong correlations with tablet porosity, indicating sensitivity to manufacturing variables.
• The model utilizes fundamental active pharmaceutical ingredient properties (solubility, particle size, density) for early-stage predictions.

Conclusions:

• The proposed compartmental model offers a robust framework for evaluating tablet dissolution performance.
• The model's ability to correlate with manufacturing parameters supports its application in real-time release testing for continuous direct compression.
• This approach facilitates early development by leveraging inherent drug substance characteristics.