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Tricaprylin microemulsion for oral delivery of low molecular weight heparin conjugates

Authors :
Kim, Sang Kyoon
Lee, Eun Hye
Vaishali, Bagalkot
Lee, Seulki
Lee, Yong-kyu
Kim, Choong-Yong
Moon, Hyun Tae
Byun, Youngro
Source :
Journal of Controlled Release. Jun2005, Vol. 105 Issue 1/2, p32-42. 11p.
Publication Year :
2005

Abstract

Abstract: Heparin is available to patients only by parenteral administrations due to its low oral bioavailability. For the oral delivery of low molecular weight heparin (LMWH), LMWH–DOCA was synthesized by chemical conjugation of LMWH and deoxycholic acid (DOCA) and this conjugate was formulated in a microemulsion system. The coupling ratios of DOCA to LMWH for LD1 and LD2 were 1.33 and 2.37, respectively. The microemulsion was composed of tricaprylin, surfactant mixture (Tween® 80 and Span® 20) and LMWH–DOCA in water, and their volume ratio was 5:3:1:1. Pharmacokinetic parameters of LMWH were not significantly changed by conjugation with DOCA; however, when LMWH–DOCA in tricaprylin microemulsion was orally administered in mice, its bioavailability was increased up to 1.5%. Furthermore, the enhancing effect of the conjugated DOCA in the tricaprylin microemulsion on the absorption of LMWH in the intestine was more significantly increased in monkey than in mice. Since the tricaprylin microemulsion could dissolve LMWH–DOCA, this formulation could maximize the enhancing effect of the conjugated DOCA on the absorption of LMWH in the intestine. Finally, it was expected that 20 mg/kg of LMWH–DOCA in the tricaprylin microemulsion was enough to prevent deep vein thrombosis (DVT) and pulmonary embolism (PE). [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
01683659
Volume :
105
Issue :
1/2
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
18013202
Full Text :
https://doi.org/10.1016/j.jconrel.2005.03.018