Tricaprylin microemulsion for oral delivery of low molecular weight heparin conjugates

Kyoon Kim Sang, Hye Lee Eun, Bagalkot Vaishali, Seulki Lee, Yong Kyu Lee, Choong Yong Kim, Tae Moon Hyun, Youngro Byun

Research output: Contribution to journalArticle

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).

Original languageEnglish (US)
Pages (from-to)32-42
Number of pages11
JournalJournal of Controlled Release
Volume105
Issue number1-2
DOIs
StatePublished - Jun 20 2005
Externally publishedYes

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Low Molecular Weight Heparin
Deoxycholic Acid
Polysorbates
Biological Availability
Intestines
tricaprylin
Pulmonary Embolism
Surface-Active Agents
Venous Thrombosis
Haplorhini
Heparin
Pharmacokinetics
Water

Keywords

  • Deoxycholic acid
  • Low molecule weight heparin
  • Microemulsion
  • Oral delivery
  • Tricaprylin

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Tricaprylin microemulsion for oral delivery of low molecular weight heparin conjugates. / Sang, Kyoon Kim; Eun, Hye Lee; Vaishali, Bagalkot; Lee, Seulki; Lee, Yong Kyu; Kim, Choong Yong; Hyun, Tae Moon; Byun, Youngro.

In: Journal of Controlled Release, Vol. 105, No. 1-2, 20.06.2005, p. 32-42.

Research output: Contribution to journalArticle

Sang, Kyoon Kim ; Eun, Hye Lee ; Vaishali, Bagalkot ; Lee, Seulki ; Lee, Yong Kyu ; Kim, Choong Yong ; Hyun, Tae Moon ; Byun, Youngro. / Tricaprylin microemulsion for oral delivery of low molecular weight heparin conjugates. In: Journal of Controlled Release. 2005 ; Vol. 105, No. 1-2. pp. 32-42.
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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{\circledR} 80 and Span{\circledR} 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).",
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AU - Sang, Kyoon Kim

AU - Eun, Hye Lee

AU - Vaishali, Bagalkot

AU - Lee, Seulki

AU - Lee, Yong Kyu

AU - Kim, Choong Yong

AU - Hyun, Tae Moon

AU - Byun, Youngro

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N2 - 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).

AB - 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).

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KW - Low molecule weight heparin

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