Minimizing the aggregation of neutral insulin solutions.

Various solution additives affect the solubility and macroaggregation of insulin in buffered aqueous solutions at physiological pH. The solubility of insulin may be improved with the addition of small amounts of aspartic acid, glutamic acid, EDTA (ethylenediaminetetraacetic acid), lysine, Tris buffer, or bicarbonate buffer. In addition, the propensity of dissolved insulin to reaggregate and precipitate may be inhibited by such additives. Buffered physiological (pH 7.4) saline solutions containing 0.001-0.003 M lysine in the presence of 0.005 M EDTA or 0.01 M lysine in the absence of EDTA improve insulin solubility and are effective in minimizing aggregation. Solutions thus prepared may be suitable for application in intravenous insulin infusion devices and may be useful commercial insulin preparations.