A dynamic in vitro lipolysis model. II: Evaluation of the model

  • Zangenberg N
  • Müllertz A
  • Gjelstrup Kristensen H
 et al. 
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A lipolysis model was characterised and evaluated by investigating the composition of the aqueous phase and the concentration of probucol and danazol in the aqueous phase. Effects of bile salt levels at 5, 10, 20, and 30 mM were investigated. Samples were taken at 0%, 50%, 75% and 95% hydrolysis of the triglycerides, and the aqueous phases were isolated by ultra-centrifugation, whereby the concentrations of bile salts, fatty acids, mono-, di-, triglycerides, and drug substances were measured. At high Ca2+-concentrations, bile salts were believed to precipitate with Ca2+. The concentration of lipolytic products (fatty acids + monoglycerides) was dependent on the bile salt concentration. The ratio between lipolytic product and bile salts was 1.55±0.09 (S.D.). This ratio is equivalent to mixed bile salt micelles and vesicles in equilibrium. The aqueous solubility of probucol and danazol was increased in the presence of bile salts. The concentration of danazol in the aqueous phase was dependent on the solubilisation capacity of the aqueous phase. In the case of probucol, the concentration in the aqueous phase was dependent on the partition of probucol between the aqueous phase and the remaining triglyceride phase. This difference between danazol and probucol was attributed to the effect of different lipophilicity. Copyright © 2001 Elsevier Science B.V.

Author-supplied keywords

  • Danazol
  • Dissolution
  • Lipolysis
  • Mixed micelles
  • Probucol

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