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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
Summary
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:
- 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.