Effect of processing and formulation factors on Catalase activity in tablets

Area of Science:

• Pharmaceutical Technology
• Biopharmaceutical Formulation
• Protein Stabilization

Background:

• Biologics manufacturing, especially tableting, causes thermal and shear stress, leading to protein denaturation and loss of activity.
• Saccharides are known protein stabilizers, but their efficacy during solid oral dosage processing remains understudied.

Purpose of the Study:

• To investigate the impact of formulation and processing variables on catalase activity and structure in tablets.
• To evaluate dextran, mannitol, and trehalose as stabilizers during tableting and spray-drying.

Main Methods:

• Preparation of non-spray-dried and spray-dried catalase formulations with different saccharides.
• Tableting formulations at varying pressures (100, 200, 400 MPa).
• Analysis of enzymatic activity, aggregate formation, and structural modifications using principal component analysis.

Main Results:

• Both tableting and spray-drying negatively impacted catalase activity and increased aggregate formation.
• Dextran and mannitol showed limited ability to preserve catalase activity across processing steps.
• Trehalose demonstrated protective effects during spray-drying but was less effective during tableting.

Conclusions:

• Formulation composition and processing parameters significantly influence biologic stability during manufacturing.
• Optimizing formulation and process variables synergistically is crucial for preserving biologic characteristics.
• Trehalose shows potential as a stabilizer, but further optimization is needed for tableting processes.