PMID- 32649984
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 152
DP  - 2020 Sep 1
TI  - Gastrointestinal diseases and their impact on drug solubility: Crohn's disease.
PG  - 105459
LID - S0928-0987(20)30248-7 [pii]
LID - 10.1016/j.ejps.2020.105459 [doi]
AB  - In order to investigate differences in drug solubilisation and dissolution in 
      luminal fluids of Crohn's disease (CD) patients and healthy subjects, biorelevant 
      media representative of CD patients were developed using information from 
      literature and a Design of Experiment (DoE) approach. The CD media were 
      characterised in terms of surface tension, osmolality, dynamic viscosity and 
      buffer capacity and compared to healthy biorelevant media. To identify which drug 
      characteristics are likely to present a high risk of altered drug solubility in 
      CD, the solubility of six drugs was assessed in CD media and solubility 
      differences were related to drug properties. Identified differences in CD 
      patients compared to healthy subjects were a reduced concentration of bile salts, 
      a higher gastric pH and a higher colonic osmolality. Differences in the 
      properties of CD compared to healthy biorelevant media were mainly observed for 
      surface tension and osmolality. Drug solubility of ionisable compounds was 
      altered in gastric CD media compared to healthy biorelevant media. For drugs with 
      moderate to high lipophilicity, a high risk of altered drug solubilisation in CD 
      is expected, since a significant negative effect of log P and a positive effect 
      of bile salts on drug solubility in colonic and fasted state intestinal CD media 
      was observed. Simulating the conditions in CD patients in vitro offers the 
      possibility to identify relevant differences in drug solubilisation without 
      conducting expensive clinical trials.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Effinger, Angela
AU  - Effinger A
AD  - Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
FAU - O'Driscoll, Caitriona M
AU  - O'Driscoll CM
AD  - School of Pharmacy, University College Cork, Cork, Ireland.
FAU - McAllister, Mark
AU  - McAllister M
AD  - Pfizer Drug Product Design, Sandwich, UK.
FAU - Fotaki, Nikoletta
AU  - Fotaki N
AD  - Department of Pharmacy and Pharmacology, University of Bath, Bath, UK. Electronic 
      address: n.fotaki@bath.ac.uk.
LA  - eng
PT  - Journal Article
DEP - 20200707
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - *Crohn Disease/drug therapy
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Osmolar Concentration
MH  - *Pharmaceutical Preparations
MH  - Solubility
OTO - NOTNLM
OT  - Biorelevant media
OT  - Crohn's disease
OT  - Gastrointestinal diseases
OT  - Inflammatory bowel disease
OT  - Physicochemical properties
OT  - Solubility
COIS- Declaration of Competing Interest None.
EDAT- 2020/07/11 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/07/11 06:00
PHST- 2020/03/27 00:00 [received]
PHST- 2020/06/12 00:00 [revised]
PHST- 2020/07/05 00:00 [accepted]
PHST- 2020/07/11 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/07/11 06:00 [entrez]
AID - S0928-0987(20)30248-7 [pii]
AID - 10.1016/j.ejps.2020.105459 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2020 Sep 1;152:105459. doi: 10.1016/j.ejps.2020.105459. Epub 
      2020 Jul 7.