Document Detail


Effect of sulfobutyl ether-β-cyclodextrin on bioavailability of insulin glargine and blood glucose level after subcutaneous injection to rats.
MedLine Citation:
PMID:  21803140     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Insulin glargine is the first long-acting basal insulin analogue used for subcutaneous administration once daily in patients with type 1 or type 2 diabetes mellitus. To obtain the further bioavailability and the sustained glucose lowering effect of insulin glargine, in the present study, we investigated the effect of sulfobutyl ether-β-cyclodextrin (SBE4-β-CyD), with the degree of substitution of sulfobutyl ether group of 3.9, on pharmaceutical properties of insulin glargine and the release of insulin glargine after subcutaneous injection to rats. SBE4-β-CyD increased the solubility and suppressed aggregation of insulin glargine in phosphate buffer at pH 9.5, probably due to the interaction of SBE4-β-CyD with aromatic amino acid residues such as tyrosine of insulin glargine. In addition, SBE4-β-CyD accelerated the dissolution rate of insulin glargine from its precipitates, compared to that of insulin glargine alone. Furthermore, we revealed that subcutaneous administration of an insulin glargine solution with SBE4-β-CyD to rats enhanced the bioavailability of insulin glargine and sustained the glucose lowering effect, possibly due to the inhibitory effects of SBE4-β-CyD on the enzymatic degradation at the injection site. These results suggest that SBE4-β-CyD can be a useful excipient for sustained release of insulin glargine.
Authors:
Keiko Uehata; Takayuki Anno; Kayoko Hayashida; Keiichi Motoyama; Fumitoshi Hirayama; Naomi Ono; James D Pipkin; Kaneto Uekama; Hidetoshi Arima
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-23
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  -     ISSN:  1873-3476     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-8-1     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. Published by Elsevier B.V.
Affiliation:
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
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