Effect on the partition equilibrium of various drugs by the formation of mixed bile salt/phosphatidylcholine/fatty acid micelles. A characterization by micellar affinity capillary electrophoresis. Part IV.
Mixed micelles, which mimic the bile containing fatty acids in the gastrointestinal tract, were used as a pseudostationary phase in capillary electrophoresis. The mixed micellar system studied contained the dihydroxy bile salts sodium glycodeoxycholate or sodium taurodeoxycholate or the trihydroxy bile salt sodium taurocholate, in association with different sodium salts of fatty acids including lauric, myristic, palmitic, oleic, stearic and linoleic acid and lecithin or dipalmitoylphosphatidylcholine as phospholipid. The determination of the changing mobilities of ionic analytes in the presence of mixed micelles reflected interactions between the used drugs and the mixed micelles. These were determined as dependence on the fatty acid concentration in the bile salt/fatty acid micelles and the mixed bile salt/phosphatidylcholine/fatty acid micelles. The capacity factor kappa MMC, for the partition between mixed micellar and aqueous phase was calculated. The partition equilibrium of basic and acidic drugs depends considerably on shape and charge of the mixed micelles (dependent on the fatty acid concentration) as well as on the acid-base properties of the drug. The mobility of the micelle aggregates was determined as an important reference value to the calculations of kappa MMC. This paper also describes the use of laser-induced fluorescence detection and electrospray mass spectrometry and tandem mass spectrometry for the characterization of the mixed micelle composition.
Institute of Pharmaceutics and Biopharmaceutics, Martin Luther University, Halle (Saale), Germany.
M A
MA
Schawrz
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K
Raith
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G
Dongowski
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RH
Neubert
D001647:Bile Acids and Salts / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019075:Electrophoresis, Capillary / Q000379:methods*; D005227:Fatty Acids / Q000737:chemistry*; D005456:Fluorescent Dyes; D013058:Mass Spectrometry; D008823:Micelles; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines; D013678:Technology, Pharmaceutical
D001647:Bile Acids and Salts; D005227:Fatty Acids; D005456:Fluorescent Dyes; D008823:Micelles; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C042077:N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine