Assessment of granulation technologies for an API with poor physical properties

Area of Science:

• Pharmaceutical Technology
• Materials Science

Background:

• Compound A, a BCS class II compound, exhibits poor physical properties like low solubility, bulk density, and flowability, hindering oral dosage form manufacturing.
• Traditional granulation techniques such as wet, dry, and melt granulation were investigated to overcome these limitations.

Purpose of the Study:

• To assess the suitability of wet, dry, and melt granulation for Compound A.
• To characterize and overcome the inherent physical property limitations of Compound A.
• To develop scalable granulation processes for improved oral dosage forms.

Main Methods:

• Characterization of Compound A's physical properties (hygroscopicity, solubility, density, flowability).
• Evaluation of high shear aqueous wet granulation, roller compaction (dry granulation), and hot melt extrusion (melt granulation).
• Process parameter optimization (e.g., roll force, roll gap) and scale-up to 10 kg.

Main Results:

• Aqueous wet granulation induced an undesirable water-mediated phase transition.
• Dry granulation via roller compaction (15 kN/cm roll force) improved granule density and flow, reducing fines from 90% to 26%, but limited drug loading to 0.6:1.
• Hot melt extrusion achieved a significant drug loading of 4:1 with reduced fines compared to other methods.

Conclusions:

• Both roller compaction and hot melt extrusion are viable, scalable granulation processes for Compound A.
• Melt granulation offers superior drug loading and reduced fines for Compound A.
• Addressing physical property limitations through appropriate granulation is crucial for developing effective oral dosage forms.