Insulin is used to treat various forms of diabetes mellitus. Patients with type I diabetes mellitus depend on external insulin, most commonly injected subcutaneously, for their survival because of the deficiency of the hormone. Insulin is typically delivered via a pen or via a miniaturised pump. Although a relatively robust peptide, there is a strong need to improve its stability in aqueous compositions at increased temperatures. In the presence of zinc cations human Insulin exists in the hexameric form.
Various insulin analogues have been developed to increase the dissociation of insulin from its hexameric form and make the insulin preparations more rapid-acting. The objective of this development programme was to demonstrate that the stability of human insulin, as well as some of the insulin analogues, can be improved by application of the ArestatT technology.
Human Insulin is a relatively stable molecule at 2-8?C in the presence of zinc. All major degradation pathways of insulin, including deamidation, aggregation and fibril formation, are known to proceed more rapidly from the monomeric or dimeric forms than from the hexameric form. The stability of all forms of insulin preparations is compromised at higher temperatures.
Several marketed insulin analogues were reformulated into new formulations based on the Arestat-TT formulation tools. The original products were used as control formulations, and all compositions contained a preservative.
It was demonstrated that the stability of the marketed analogues of insulin, both zinc-complexed and zinc-free, can be dramatically improved at 40?C using the principles of the ArestatT technology. A considerably better retention of the native form of insulin, assessed by reverse phase-HPLC, was demonstrated in all cases.