Insulin precipitation in artificial infusion devices

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Chemical Engineering

Background:

• Insulin precipitation poses a significant challenge for mechanical insulin infusion devices, impacting therapeutic efficacy.
• Understanding the factors influencing insulin precipitation is crucial for developing stable insulin formulations for continuous delivery.

Purpose of the Study:

• To investigate conditions affecting insulin precipitation in a simulated mechanical insulin infusion system.
• To identify strategies for minimizing insulin precipitation during prolonged infusion therapy.

Main Methods:

• Utilized a recirculating system with a peristaltic pump to mimic insulin infusion.
• Evaluated insulin precipitation under various pH conditions (2, 3, 7, 8) and buffer types (acetate, phosphate).
• Assessed the impact of EDTA-treated tubing versus untreated tubing on insulin stability.

Main Results:

• Acetate buffer and neutral pH (7) with untreated tubing led to over 95% insulin precipitation within ten days.
• Phosphate buffer at neutral pH with EDTA-treated tubing prevented insulin precipitation over ten days.
• Heavy metal-insulin association identified as a major precipitation factor; insulin fibril formation also suggested.

Conclusions:

• Phosphate-buffered, highly purified porcine insulin is suitable for prolonged infusion.
• Minimizing metal ion contamination in the delivery system is critical for preventing insulin precipitation.
• EDTA pretreatment of tubing significantly enhances insulin stability in infusion devices.