Minimizing the aggregation of neutral insulin solutions

Area of Science:

• Biochemistry
• Pharmaceutical Science

Background:

• Insulin is a crucial hormone for glucose regulation.
• Insulin's stability in solution is critical for therapeutic applications.
• Aggregation and precipitation of insulin can limit its efficacy and shelf-life.

Purpose of the Study:

• To investigate the effects of various solution additives on insulin solubility and aggregation.
• To identify optimal conditions for preparing stable insulin solutions at physiological pH.

Main Methods:

• Testing the solubility of insulin in buffered aqueous solutions with different additives.
• Evaluating the aggregation and precipitation of insulin in the presence of these additives.
• Utilizing buffered physiological saline solutions (pH 7.4) with specific concentrations of lysine and EDTA.

Main Results:

• Aspartic acid, glutamic acid, ethylenediaminetetraacetic acid (EDTA), lysine, Tris buffer, and bicarbonate buffer were found to improve insulin solubility.
• These additives also inhibited the reaggregation and precipitation of dissolved insulin.
• Specific formulations, such as 0.001-0.003 M lysine with 0.005 M EDTA, or 0.01 M lysine alone, significantly enhanced solubility and minimized aggregation.

Conclusions:

• Solution additives can effectively improve insulin solubility and prevent aggregation in buffered physiological solutions.
• Optimized insulin solutions demonstrate potential for use in intravenous insulin infusion devices.
• These findings suggest the development of improved commercial insulin preparations.