Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Direct compression is a preferred tableting method for its efficiency.
• Amorphous solid forms can offer improved drug solubility but often present stability and processing challenges.

Purpose of the Study:

• To evaluate the stability and processability of amorphous olanzapine (OLZ) and its co-amorphous form with saccharin (SAC) during direct compression tableting.
• To compare the properties of tablets containing amorphous/co-amorphous OLZ with those containing crystalline OLZ.

Main Methods:

• Characterization of powder flowability and compressibility.
• Tablet manufacturing via direct compression.
• Stability assessment using X-ray powder diffraction (XRPD), Fourier-transform infrared (FTIR), and near-infrared (NIR) spectroscopies.
• Drug release studies.

Main Results:

• Amorphous and co-amorphous OLZ powders exhibited reduced flowability due to increased cohesiveness compared to crystalline OLZ.
• Tablets maintained long-lasting amorphous OLZ with enhanced water solubility.
• Drug release rate from amorphous/co-amorphous OLZ tablets was slower than from crystalline OLZ tablets.
• High compaction pressure (155 MPa) and dwell time (5 min) facilitated significant amorphization (approx. 20%) in physical mixtures.

Conclusions:

• Amorphous and co-amorphous OLZ demonstrate good stability during direct compression tableting.
• Compaction pressure positively influences the formation of co-amorphous OLZ, presenting a potential expedited amorphization technique.
• Process development challenges need to be addressed for practical implementation.