Pseudo-ternary phase diagrams of aqueous mixtures of Quil A, cholesterol and phospholipid prepared by the lipid-film hydration method

Patrick H Demana, Nigel M Davies, Uwe Vosgerau, Thomas Rades

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Abstract

Pseudo-ternary phase diagrams of the polar lipids Quil A, cholesterol (Chol) and phosphatidylcholine (PC) in aqueous mixtures prepared by the lipid film hydration method (where dried lipid film of phospholipids and cholesterol are hydrated by an aqueous solution of Quil A) were investigated in terms of the types of particulate structures formed therein. Negative staining transmission electron microscopy and polarized light microscopy were used to characterize the colloidal and coarse dispersed particles present in the systems. Pseudo-ternary phase diagrams were established for lipid mixtures hydrated in water and in Tris buffer (pH 7.4). The effect of equilibration time was also studied with respect to systems hydrated in water where the samples were stored for 2 months at 4 degrees C. Depending on the mass ratio of Quil A, Chol and PC in the systems, various colloidal particles including ISCOM matrices, liposomes, ring-like micelles and worm-like micelles were observed. Other colloidal particles were also observed as minor structures in the presence of these predominant colloids including helices, layered structures and lamellae (hexagonal pattern of ring-like micelles). In terms of the conditions which appeared to promote the formation of ISCOM matrices, the area of the phase diagrams associated with systems containing these structures increased in the order: hydrated in water/short equilibration period
Original languageEnglish
JournalInternational Journal of Pharmaceutics
Volume270
Issue number1-2
Pages (from-to)229-39
Number of pages11
ISSN0378-5173
Publication statusPublished - 11 Feb 2004
Externally publishedYes

Keywords

  • Adjuvants, Immunologic
  • Chemistry, Pharmaceutical
  • Cholesterol
  • Colloids
  • Drug Compounding
  • Microscopy, Electron
  • Phosphatidylcholines
  • Saponins
  • Water

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