Solubility changes on mixing short- and long-acting insulin preparations

The loss of solubility of short-acting insulins when mixed in a ratio of 1:1 with intermediate-acting insulins in vitro was determined using high-performance liquid chromatography. Insulin preparations (porcine and human) from three different manufacturers were tested and various times of mixing (0-24 h) were investigated. The loss of solubility with mixtures of human insulins and with mixtures of porcine Velosulin (Nordisk) and Insulatard (Nordisk) was small at all the times used. A mixture of porcine Actrapid MC (Novo) and Monotard MC (Novo) led to a 60-95% loss of the soluble component, depending on the duration of mixing. The greater the time the greater the loss. These in vitro data indicate that short-acting insulins may lose solubility when mixed with long- or intermediate-acting ones. This phenomenon could be clinically relevant when patients are changed from mixtures of monocomponent to human insulins.