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Related Experiment Videos

The effect of ionic strength on liposome-buffer and 1-octanol-buffer distribution coefficients

R P Austin1, P Barton, A M Davis

  • 1Department of Physical and Metabolic Sciences, Astra Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, United Kingdom. Rupert.Austin@charnwood.gb.astra.com

Journal of Pharmaceutical Sciences
|May 20, 1998
PubMed
Summary

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The distribution of ionized drugs like salmeterol and proxicromil in liposomes depends on ionic strength and drug concentration. Gouy-Chapman theory explains these variations, crucial for accurate liposome drug delivery studies.

Area of Science:

  • Pharmacology
  • Physical Chemistry
  • Biophysics

Background:

  • Understanding drug distribution in liposomes is vital for drug delivery systems.
  • Ionized lipophilic compounds can interact with neutral lipid bilayers, affecting their distribution.

Purpose of the Study:

  • To investigate the distribution of salmeterol and proxicromil between unilamellar vesicles of dioleoylphosphatidylcholine (DOPC) and aqueous buffer.
  • To analyze how compound concentration, DOPC concentration, and buffer ionic strength influence this distribution.

Main Methods:

  • Ultrafiltration method was employed to study compound distribution.
  • Gouy-Chapman theory was used to model the observed variations in membrane distribution coefficients.

Main Results:

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  • The binding of ionized drugs to neutral DOPC vesicles induces a surface charge, causing significant variations in the observed membrane distribution coefficient (D(mem)obs).
  • Ionic strength influences the distribution coefficient (D(mem)obs) and the 1-octanol-buffer distribution coefficient (D(o/w)obs) through different mechanisms.
  • The neutral compound clofibrate exhibited ideal behavior, contrasting with the ionized compounds.

Conclusions:

  • Determining concentration-independent liposome distribution coefficients for ionized lipophilic compounds is experimentally challenging.
  • The study provides insights into correcting observed values and suggests optimal experimental conditions for accurate measurements.