Document Detail


Peak-less hypoglycemic effect of insulin glargine by complexation with maltosyl-β-cyclodextrin.
MedLine Citation:
PMID:  22020273     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Keiko Uehata; Takayuki Anno; Kayoko Hayashida; Taishi Higashi; Keiichi Motoyama; Fumitoshi Hirayama; Kaneto Uekama; Hidetoshi Arima
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-15
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  -     ISSN:  1873-3476     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
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