2. Liposomes as Intravenous Solubilizers for Poorly Water-Soluble Drugs

  1. Dennis Douroumis1 and
  2. Alfred Fahr2
  1. Peter van Hoogevest,
  2. Mathew Leigh and
  3. Alfred Fahr

Published Online: 4 FEB 2013

DOI: 10.1002/9781118444726.ch2

Drug Delivery Strategies for Poorly Water-Soluble Drugs

Drug Delivery Strategies for Poorly Water-Soluble Drugs

How to Cite

Hoogevest, P. v., Leigh, M. and Fahr, A. (2013) Liposomes as Intravenous Solubilizers for Poorly Water-Soluble Drugs, in Drug Delivery Strategies for Poorly Water-Soluble Drugs (eds D. Douroumis and A. Fahr), John Wiley & Sons Ltd, Oxford, UK. doi: 10.1002/9781118444726.ch2

Editor Information

  1. 1

    School of Science, University of Greenwich, UK

  2. 2

    Friedrich-Schiller University of Jena, Germany

Publication History

  1. Published Online: 4 FEB 2013
  2. Published Print: 21 JAN 2013

ISBN Information

Print ISBN: 9780470711972

Online ISBN: 9781118444726

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Keywords:

  • Liposome;
  • Lipid composition;
  • Solubilizer;
  • Instant solubilization technique;
  • Drug transfer;
  • Preclinical parenteral assessment;
  • Modelling

Summary

The intravenous administration of poorly water-soluble compounds is problematic. Traditional formulation approaches, such as the use of co-solvents, pH adjustment, surfactants, or cyclodextrins, carry the risk of precipitation of the poorly water-soluble compounds upon dilution in the blood circulation, and may pose toxicity and patent-related industrial development risks. Lipid-based solubilizing vehicles such as oil-in-water emulsions, mixed micelles and liposomes may present more elegant solubilizing formulations because they maintain their solubilizing capacity upon dilution in the blood circulation and reduce or delay tendencies for precipitation. In this chapter, the interaction and release (transfer) properties of poorly water-soluble compounds in combination with liposomes as solubilizers are reviewed. In particular, in vitro release methods, in vivo mechanisms, and thermodynamic aspects are discussed. Also the influence of the type of drug, the lipid dose, the liposome type and the composition on the in vivo transfer kinetics of associated poorly water-soluble compounds are reviewed. The advent of an instantaneous solubilization method, which uses pre-fabricated liposomes to which the drug is added in minor volume of a pharmaceutically acceptable water-miscible organic solvent, allows the speedy testing at pre-clinical laboratories of liposomes as a solubilizer for poorly water-soluble compounds without the risk of precipitation and interfering toxicity of the used excipients. Following the release mechanisms described above, the liposome formulations can also be used to optimize the pharmacokinetics of the poorly water-soluble compounds to achieve a better therapeutic profile and less toxicity.