Physical stability of insulin formulations

Area of Science:

• Biomaterials Science
• Pharmaceutical Formulation

Background:

• Insulin aggregation is a major challenge for long-term use in insulin infusion systems.
• Understanding factors influencing insulin stability is crucial for developing effective delivery devices.

Purpose of the Study:

• To investigate the impact of various compounds on the aggregation behavior of crystalline zinc insulin (CZI).
• To identify stabilizers that can prevent insulin aggregation under simulated delivery conditions.

Main Methods:

• CZI solutions at different concentrations (5-500 U/ml) were subjected to simulated severe conditions (air, motion, elevated temperature).
• The effect of various physiologic and nonphysiologic compounds, including surfactants and alcohols, on CZI aggregation was assessed by measuring turbidity (transmittance at 540 nm).
• Interactions with medical-grade materials like silicone rubber were also evaluated.

Main Results:

• At 5 U/ml, CZI formed turbid gels within 5 days under harsh conditions.
• Formulations with specific anionic and nonionic surfactants (e.g., SDS, Brij 35, Tween, Triton X) and lysophosphatidylcholine showed high transmittance (>96%) for 67-150 days.
• Surfactants with hydrophobic chains (N=7-16) were most effective; alcohols provided moderate stabilization.
• Silicone rubber significantly accelerated aggregation, except in 1% SDS formulations.

Conclusions:

• Insulin aggregation can be inhibited by reducing the effective polarity of the solvent, particularly using anionic and nonionic surfactants with long hydrophobic groups.
• Certain surfactants offer remarkable stabilization for CZI solutions in delivery systems.
• Silicone rubber poses a risk for promoting insulin aggregation in medical devices.