Dissolution of hydrocortisone in human and simulated intestinal fluids

• Published in: Pharmaceutical research Vol. 17; no. 2; pp. 183 - 189
• Main Authors: PEDERSEN, B. L, BRØNDSTED, H, LENNERNÄS, H, CHRISTENSEN, F. N, MÜLLERTZ, A, KRISTENSEN, H. G
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-02-2000; Springer Nature B.V
• Subjects: Anti-Inflammatory Agents - pharmacokinetics; Bile; Biological and medical sciences; Body Fluids; Bones, joints and connective tissue. Antiinflammatory agents; Buffers; Contact angle; Diffusion; Dissolution; Drugs; Duodenum - metabolism; Eating; Fasting; Fatty acids; Fluids; General pharmacology; Glycerol; Glycocholic Acid - chemistry; Glycocholic Acid - metabolism; Humans; Hydrocortisone - pharmacokinetics; Hydrogen-Ion Concentration; Intestinal Absorption - physiology; Jejunum - metabolism; Medical sciences; Micelles; Osmotic Pressure; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Rheology; Salt; Small intestine; Sodium; Solubility; Surface Tension; Surfactants; Denmark; United States > US; Sweden; Human; Corticosteroid; Biological fluid; Digestive system; Steroid hormone; Bile salt; Antiinflammatory agent; Gut; Intestinal juice; Solubility; Phospholipid; Hydrodynamics; Lipids; Lipophily; Surfactant; Hydrocortisone; Fatty acids; Dissolution; In vitro; Monoglyceride; Simulation; Adrenal hormone; Diffusion
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1007517414200

To compare solubility and dissolution rate of hydrocortisone in aspirated human intestinal fluids (HIFs) with simulated intestinal fluids (SIFs) and buffer.
Solubility and flux from a rotating disk of hydrocortisone were measured. The bile salt content, pH and osmotic pressure were determined in HIFs.
In fasted state the solubility of hydrocortisone was higher in HIFs than in the buffer and SIFs. The flux of hydrocortisone in HIFs was similar to the flux in the buffer but lower than the flux in SIFs at fasted state. Addition of intestinal surfactants in SIFs increased solubility and flux at both fasted and fed state. The increase in solubility was caused by micelle formation in SIFs. The increase in flux may partly be explained by increased solubility. The bile salt content of the HIFs did not correlate with the solubility or the flux but pH in the HIFs seems to have some effect on the components of the HIFs resulting in increased solubility.
It is possible to perform comparable dissolution tests in HIFs and SIFs. The lack of correlation between the results in HIFs and the bile salt content may be explained by the relatively low lipophilicity of the model drug.