WFRF:(Bergström Christel A. S.)
Sökning: WFRF:(Bergström Christel A. S.) > (2010-2014) > Ethanol Effects on ...
- Fagerberg, Jonas H.Uppsala universitet,Institutionen för farmaci (författare)
Ethanol Effects on Apparent Solubility of Poorly Soluble Drugs in Simulated Intestinal Fluid
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
- 2012-06-20
- American Chemical Society (ACS),2012
- printrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:uu-178097
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-178097URI
- https://doi.org/10.1021/mp2006467DOI
Kompletterande språkuppgifter
- Språk:engelska
- Sammanfattning på:engelska
Ingår i deldatabas
- SwePubSwePub
Klassifikation
Anmärkningar
- Ethanol intake can lead to an unexpected and possibly problematic increase in the bioavailability of druglike compounds. In this work we investigated the effect of ethanol on the apparent solubility and dissolution rate of poorly soluble compounds in simulated intestinal fluid representing a preprandial state. A series of 22 structurally diverse, poorly soluble compounds were measured for apparent solubility and intrinsic dissolution rate (37 degrees C) in phosphate buffer pH 6.5 (PhB6.5) and fasted state simulated intestinal fluid (FaSSIF, pH 6.5) with and without ethanol at 5% v/v or 20% v/v. The obtained data were used to understand for which molecules ethanol results in an increased apparent solubility and, therefore, may increase the amount of drug absorbed. In FaSSIF(20%ethanol) 59% of the compounds displayed >3-fold higher apparent solubility than in pure FaSSIF, whereas the effects of 5% ethanol on solubility, in most cases, were negligible. Acidic and neutral compounds were more solubilized by the addition of ethanol than by lecithin/taurocholate aggregates, whereas bases showed a more substance-specific response to the additives in the buffer. The stronger solubilizing capacity of ethanol as compared to the mixed lipid aggregates in FaSSIF was further identified through Spearman rank analyses, which showed a stronger relationship between FaSSIF(20%ethanol) and PhB6.5,20%ethanol (r(S) of 0.97) than FaSSIF(20%ethanol) and FaSSIF (r(S) of 0.86). No relationships were found between solubility changes in media containing ethanol and single physicochemical properties, but multivariate data analysis showed that inclusion of ethanol significantly reduced the negative effect of compound lipophilicity on solubility. For this data set the higher concentration of ethanol gave a dose number (Do) <1 for 30% of the compounds that showed incomplete dissolution in FaSSIF. Significant differences were shown in the melting point, lipophilicity, and dose profiles between the compounds having a Do < 1 and Do > 1, with the latter having higher absolute values in all three parameters. In conclusion, this study showed that significant effects of ethanol on apparent solubility in the preprandial state can be expected for lipophilic compounds. The results herein indicate that acidic and neutral compounds are more sensitive to the addition of ethanol than to the mixed lipid aggregates present in the fasted intestine.
Ämnesord och genrebeteckningar
- apparent solubility
- dissolution rate
- ethanol
- biorelevant dissolution medium
- poorly soluble compounds
- molecular properties
- dose number
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Al-Tikriti, YassirUppsala universitet,Institutionen för farmaci(Swepub:uu)yasal749 (författare)
- Ragnarsson, Gert (författare)
- Bergström, Christel A. S.Uppsala universitet,Institutionen för farmaci(Swepub:uu)cjo29958 (författare)
- Uppsala universitetInstitutionen för farmaci (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Molecular Pharmaceutics: American Chemical Society (ACS)9:7, s. 1942-19521543-83841543-8392
Internetlänk
Hitta via bibliotek
- Molecular Pharmaceutics (Sök värdpublikationen i LIBRIS)
Till lärosätets databas
Hitta mer i SwePub
- Av författaren/redakt...
- Fagerberg, Jonas ...
- Al-Tikriti, Yass ...
- Ragnarsson, Gert
- Bergström, Chris ...
- Artiklar i publikationen
- Molecular Pharma ...
- Av lärosätet
- Uppsala universitet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
