A moving-boundary model of dissolution from binary drug-excipient granules incorporating microstructure

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Drug release from granules is crucial for formulation development.
• Granulation processes can introduce variations in granule porosity and drug load.
• Existing models may not fully capture these variations.

Purpose of the Study:

• To analyze and validate a mechanistic model for drug release from single spherical granules.
• To incorporate radial variations in porosity and drug load within the model.
• To extend the model for polydisperse granule collections and compare it with existing methods.

Main Methods:

• Model development and specialization for high drug load scenarios.
• Validation using literature data for acetaminophen and microcrystalline cellulose granules.
• Derivation of an extended model for polydisperse systems and comparison with single particle models.

Main Results:

• The model accurately describes drug release from granules with radially varying porosity and drug load.
• The specialized model simplifies to an ODE for a shrinking, drug-saturated core.
• The extended model shows improved performance for polydisperse systems compared to equivalent spherical diameter models.

Conclusions:

• The developed model offers a novel tool for exploring dissolution parameter space.
• It allows for the consideration of manufacturing-induced variations in granule properties.
• This enhances the understanding and prediction of drug release behavior in pharmaceutical formulations.