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Estimation Of The Increase In Solubility Of Drugs As A Function Of Bile Salt Concentration
S. D. Mithani, V. Bakatselou, C. TenHoor, J. Dressman
Published 2004 · Medicine, Chemistry
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AbstractPurpose. The objective of this study was to develop a model to predict the extent to which bile salts can enhance the solubility of a drug, based on the physicochemical properties of the compound. The ability to predict bile salt solubilization of poorly soluble drugs would be a key component in determining which drugs will exhibit fed vs. fasted differences in drug absorption. Methods. A correlation between the logarithm of the octanol/water partition coefficient [log P] of six steroidal compounds and their solubilities in the presence of various concentrations of sodium taurocholate at 37°C, log [SR] = 2.234 + 0.606log [P] (r2 = 0.987) where SR is the ratio of the solubilization capacity of the bile salt to the solubilization capacity of water for the drug, was used to predict the solubility of five further compounds with diverse structures. The solubilities of the compounds in presence of sodium taurocholate were then measured. Results. The predicted solubilities were within 10% of the experimentally observed solubilities for griseofulvin, cyclosporin A and pentazocine. The model overpredicted the solubility of phenytoin and diazepam in 15 mM sodium taurocholate solution by a factor of 1.33 and 1.62 respectively. Conclusions. The expected increase in solubility as a function of bile salt concentration can be estimated on the basis of the partition coefficient and aqueous solubility of the compound.
This paper references
Influence of bile on the gastrointestinal absorption of phenytoin in rats.
D. Shinkuma (1985)
Remington's pharmaceutical sciences
J. P. Remington (1985)
Micellar solubilization of barbiturates. I. Solubilities of certain barbiturates in polysorbates of varying hydrophobic chain length.
A. A. Ismail (1970)
Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects.
A. Tangerman (1986)
Bile acid output and the interdigestive migrating motor complex in normals and in cholecystectomy patients
T. Peeters (1980)
Solubilization of benzoic acid derivatives by polyoxyethylene lauryl ether.
H. Tomida (1978)
The rate of solution of solid substances in their own solutions
A. A. Noyes (1897)
Micellar Solubilization of Clofazimine Analogues in Aqueous Solutions of Ionic and Nonionic Surfactants
K. M. S. Fahelelbom (2004)
Duodenal bile acids after a test meal.
O. Fausa (1974)
Solubilization of steroid hormones by polyoxyethylene lauryl ether.
H. Tomida (1978)
Rate of Dissolution of Griseofulvin and Hexoestrol in Bile Salt Solutions
THEODORE R. Bates (1966)
Determination of partition coefficients of glucocorticosteroids by high-performance liquid chromatography.
J. C. Caron (1984)
An examination of acid‐base equilibria of 1,4‐benzodiazepines by spectrophotometry
J. Barrett (1973)
Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: evidence from partition coefficients and molecular dynamics simulations.
N. El Tayar (1993)
Dissolution mechanisms of poorly soluble compounds in simple and mixed micelle systems.
L. J. Naylor (1993)
Drug interactions occurring during absorption from the gastrointestinal tract.
J. Griffin (1981)
Micelle formation by bile salts. Physical-chemical and thermodynamic considerations.
M. Carey (1972)
Solubilization and Wetting Effects of Bile Salts on the Dissolution of Steroids
V. Bakatselou (2004)
Human pharmacology of griseofulvin: the effect of fat intake on gastrointestinal absorption.
R. G. Crounse (1961)
Upper Gastrointestinal (GI) pH in Young, Healthy Men and Women
J. Dressman (2004)
Partition coefficients and their uses
Albert J. Leo (1971)
Effect of a high-fat meal on the bioavailability of phenytoin in a commercial powder with a large particle size.
Tomoyuki Hamaguchi (1993)
Influence of Food on the Bioavailability of Drugs
A. Melander (1978)
Effect of Food and a Monoglyceride Emulsion Formulation on Danazol Bioavailability
W. Charman (1993)
Solubilization of hydrocortisone, dexamethasone, testosterone and progesterone by long‐chain polyoxyethylene surfactants
B. Barry (1976)
Interaction of substituted benzoic acids with polysorbate 20 micelles.
John H. Collett (1975)
Surfactant Systems: Their chemistry, pharmacy and biology
D. Attwood (1983)
Physiologic surface-active agents and drug absorption. IV. Effect of pre-micellar concentrations of surfactant on dissolution rate.
H. Weintraub (1969)
Solubility and ionization characteristics of phenytoin.
P. A. Schwartz (1977)
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Lilly Roy (2013)
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Ligeng Yin (2014)
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A. Avdeef (2007)
New findings on melatonin absorption and alterations by pharmaceutical excipients using the Ussing chamber technique with mounted rat gastrointestinal segments.
H. Tran (2009)
Overview of factors affecting oral drug absorption
Naining Song (2004)
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Chunhui Chen (2013)
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Greg A Kossena (2003)
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T. Ishihara (2010)
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Dimitrios G. Fatouros (2008)
Biliary Excretion-Mediated Food Effects and Prediction.
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P. Srinarong (2011)
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E. Rytting (2008)
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