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Fasted and fed stat...
Fasted and fed state human duodenal fluids : Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability
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- Dahlgren, David (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Venczel, M. (författare)
- Global CMC Dev Sanofi, Frankfurt, Germany.;Global CMC Dev Sanofi, Vitry Sur Seine, France.
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Ridoux, J. -P (författare)
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- Skjöld, C. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Müllertz, A. (författare)
- Univ Copenhagen, Physiol Pharmaceut, Copenhagen, Denmark.
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- Holm, R. (författare)
- Johnson & Johnson, Drug Prod Dev, Janssen R&D, Beerse, Belgium.
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- Augustijns, P. (författare)
- Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.
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- Hellström, Per M., 1954- (författare)
- Uppsala universitet,Gastroenterologi/hepatologi
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- Lennernäs, Hans (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- Elsevier, 2021
- 2021
- Engelska.
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 163, s. 240-251
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Abstract
Ämnesord
Stäng
- Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Bioavailability
- Food effects
- Drug solubility
- Human intestinal fluids
- Drug absorption
- Drug dissolution
- Drug delivery
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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