A dynamic in vitro lipolysis model
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This paper presents a new dynamic *in vitro* model designed to simulate lipolysis and study its effects on cell physiology.
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Abstract
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 Ca(2+)-concentrations, bile salts were believed to precipitate with Ca(2+). 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.
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Cited by (7)
- Exploring the Impact of Intestinal Fluid Components on the Solubility and Supersaturation of Danazol 2021
- Danazol oral absorption modelling in the fasted dog: An example of mechanistic understanding of formulation effects on drug pharmacokinetics 2019
- <i>In Vivo</i> Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems 2016
- Evaluation of the Impact of Surfactant Digestion on the Bioavailability of Danazol after Oral Administration of Lipidic Self-Emulsifying Formulations to Dogs 2007
- Increasing the Proportional Content of Surfactant (Cremophor EL) Relative to Lipid in Self-emulsifying Lipid-based Formulations of Danazol Reduces Oral Bioavailability in Beagle Dogs 2007
- Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug 2005
- In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media 2005
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