Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability

A.R. Mohammed, N. Weston, A.G.A. Coombes, M. Fitzgerald, Y. Perrie

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

Liposomes due to their biphasic characteristic and diversity in design, composition and construction, offer a dynamic and adaptable technology for enhancing drug solubility. Starting with equimolar egg-phosphatidylcholine (PC)/cholesterol liposomes, the influence of the liposomal composition and surface charge on the incorporation and retention of a model poorly water soluble drug, ibuprofen was investigated. Both the incorporation and the release of ibuprofen were influenced by the lipid composition of the multi-lamellar vesicles (MLV) with inclusion of the long alkyl chain lipid (dilignoceroyl phosphatidylcholine (C24PC)) resulting in enhanced ibuprofen incorporation efficiency and retention. The cholesterol content of the liposome bilayer was also shown to influence ibuprofen incorporation with maximum ibuprofen incorporation efficiency achieved when 4 μmol of cholesterol was present in the MLV formulation. Addition of anionic lipid dicetylphosphate (DCP) reduced ibuprofen drug loading presumably due to electrostatic repulsive forces between the carboxyl group of ibuprofen and the anionic head-group of DCP. In contrast, the addition of 2 μmol of the cationic lipid stearylamine (SA) to the liposome formulation (PC:Chol – 16 μmol:4 μmol) increased ibuprofen incorporation efficiency by approximately 8%. However further increases of the SA content to 4 μmol and above reduced incorporation by almost 50% compared to liposome formulations excluding the cationic lipid. Environmental scanning electron microscopy (ESEM) was used to dynamically follow the changes in liposome morphology during dehydration to provide an alternative assay of liposome stability. ESEM analysis clearly demonstrated that ibuprofen incorporation improved the stability of PC:Chol liposomes as evidenced by an increased resistance to coalescence during dehydration. These finding suggest a positive interaction between amphiphilic ibuprofen molecules and the bilayer structure of the liposome.
LanguageEnglish
Pages23-34
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume285
Issue number1-2
DOIs
Publication statusPublished - 5 Nov 2004

Fingerprint

Ibuprofen
Liposomes
Electron Scanning Microscopy
Water
Pharmaceutical Preparations
Phosphatidylcholines
Lipids
Cholesterol
Dehydration
Static Electricity
Solubility
Ovum
Technology

Keywords

  • environmental scanning electron microscopy
  • stability
  • poorly water soluble drug
  • liposomes
  • ibuprofen

Cite this

Mohammed, A.R. ; Weston, N. ; Coombes, A.G.A. ; Fitzgerald, M. ; Perrie, Y. / Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability. In: International Journal of Pharmaceutics. 2004 ; Vol. 285, No. 1-2. pp. 23-34.
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Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability. / Mohammed, A.R.; Weston, N.; Coombes, A.G.A.; Fitzgerald, M.; Perrie, Y.

In: International Journal of Pharmaceutics, Vol. 285, No. 1-2, 05.11.2004, p. 23-34.

Research output: Contribution to journalArticle

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T1 - Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability

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AU - Weston, N.

AU - Coombes, A.G.A.

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AU - Perrie, Y.

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