The effect of compactional pressure on urease activity

Area of Science:

• Biochemistry
• Pharmaceutical Sciences
• Materials Science

Background:

• Controlled-release drug delivery systems are crucial for peptide and polypeptide therapeutics.
• Protein drugs, like urease, may lose activity during manufacturing processes such as compaction.
• Urease serves as a model protein to study the effects of compaction on enzyme activity.

Purpose of the Study:

• To investigate the impact of compaction pressure on the activity of jack bean urease.
• To determine the pressure threshold at which urease activity is compromised during dry compaction.
• To assess the potential of compacted urease as a model for developing stable, controlled-release protein formulations.

Main Methods:

• Tablets of jack bean urease (100 mg) were compressed at pressures ranging from 60 to 1750 MPa.
• Enzyme activity was measured before and after compaction to assess relative activity loss.
• The relationship between compaction pressure and enzyme inactivation was analyzed.

Main Results:

• Jack bean urease maintained its activity up to a compaction pressure of 474 MPa.
• Compaction pressures exceeding 474 MPa resulted in a 50% loss of relative urease activity.
• No direct correlation was found between applied stress (compactional pressure) and the degree of inactivation.

Conclusions:

• Urease activity is preserved under moderate compaction pressures, suggesting potential for stable compressed formulations.
• High compaction pressures significantly affect protein structure and activity, indicating a critical threshold for processing.
• These findings provide insights into the challenges of formulating protein-based drugs for controlled release via compaction.