Long-acting insulin products are desired that provide sustained blood glucose lowering without blood glucose level peaks. In the present study, to obtain the more desirable blood glucose lowering effect of long-acting insulin products, we investigated the effect of maltosyl-β-cyclodextrin (G(2)-β-CyD) on physicochemical properties and pharmacokinetics/pharmacodynamics of insulin glargine, which is the one of the most widely used insulin analog. G(2)-β-CyD increased the solubility and suppressed the aggregation of insulin glargine in phosphate buffer at 9.5, probably due to the interaction of G(2)-β-CyD with aromatic residues of the insulin glargine such as tyrosine. In addition, the dissolution rates of insulin glargine from its precipitates were increased by a complexation with G(2)-β-CyD. Subcutaneous administration of an insulin glargine solution with G(2)-β-CyD to rats gradually decreased blood glucose levels and provided a sustained blood glucose lowering effect without showing the glucose level peaks. These results suggest that G(2)-β-CyD can be a useful excipient for sustained release and a truly peak-less formulation of insulin glargine.
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