The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine
Abstract
Solubility and dissolution relationships in the gastrointestinal tract can be critical for the oral bioavailability of poorly soluble drugs. In the case of poorly soluble weak bases, the possibility of drug precipitation upon entry into the small intestine may also affect the amount of drug available for uptake through the intestinal mucosa. To simulate the transfer out of the stomach into the intestine, a transfer model was devised, in which a solution of the drug in simulated gastric fluid is continuously pumped into a simulated intestinal fluid, and drug precipitation in the acceptor medium is examined via concentration–time measurements. The in-vitro precipitation of three poorly soluble weakly basic drugs, dipyridamole, BIBU 104 XX and BIMT 17 BS, was investigated. For all three, extensive supersaturation was achieved in the acceptor medium. Under simulated fasted-state conditions, precipitation occurred for all three compounds whereas under simulated fed-state conditions, the higher concentrations of bile components and the lower pH value in the acceptor medium inhibited precipitation at concentrations corresponding to usual doses in all cases. Comparison with pharmacokinetic data indicated that a combination of transfer model data with solubility and dissolution profiles should lead to better predictions of in-vivo behaviour of poorly soluble weak bases.
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Cites
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Cited by
Pouton, C. W. (2006) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2006.04.016 · Cited by 1,293
Review: physical chemistry of solid dispersions
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Population-Based Mechanistic Prediction of Oral Drug Absorption
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In vitro models for the prediction of in vivo performance of oral dosage forms
Kostewicz, E. S., Abrahamsson, B., Brewster, M., Brouwers, J., Butler, J., Carlert, S., Dickinson, P. A., Dressman, J., Holm, R., Klein, S., et al. (2014) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.08.024 · Cited by 373
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Metadata
- Authors
- Kostewicz, E. S., Wunderlich, M., Brauns, U., Becker, R., Bock, T., & Dressman, J. B.
- Venue
- Journal of Pharmacy and Pharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-01
- Volume
- 56
- Issue
- 1
- Pages
- 43-51
- ISSN
- 0022-3573 (ISSN-L)
- 2042-7158
- OpenAlex
- W1964575627
- Cited by
- 318
- References
- 17
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kostewicz, E. S., Wunderlich, M., Brauns, U., Becker, R., Bock, T., & Dressman, J. B. (2004). Predicting the precipitation of poorly soluble weak bases upon entry in the small intestine. Journal of Pharmacy and Pharmacology. https://doi.org/10.1211/0022357022511
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