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- Jung, Min-SookChungnam National University (författare)
Bioavailability of indomethacin-saccharin cocrystals
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
- 2010-10-11
- Oxford University Press (OUP),2010
- printrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:ltu-13905
- https://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-13905URI
- https://doi.org/10.1111/j.2042-7158.2010.01189.xDOI
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- Språk:engelska
- Sammanfattning på:engelska
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- SwePubSwePub
Klassifikation
Anmärkningar
- Validerad; 2010; 20101029 (ysko)
- Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee (R).MethodsScale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.Key findingsThe bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee (R) at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P < 0.05) than that of IND but not significantly different from Indomee (R) (ANOVA, P > 0.05).ConclusionsThe study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Annan hälsovetenskap hsv//swe
- MEDICAL AND HEALTH SCIENCES Health Sciences Other Health Sciences hsv//eng
- bioavailability
- cocrystals
- dissolution
- indomethacin
- salts
- Health Science
- Hälsovetenskap
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Kim, Jeong-SooChungnam National University (författare)
- Kim, Min-SooChungnam National University (författare)
- Alhalaweh, AmjadLuleå tekniska universitet,Medicinsk vetenskap(Swepub:ltu)amjalh (författare)
- Cho, WonkyungChungnam National University (författare)
- Hwang, Sung-JooChungnam National University (författare)
- Velaga, SitaramLuleå tekniska universitet,Medicinsk vetenskap(Swepub:ltu)sitvel (författare)
- Chungnam National UniversityMedicinsk vetenskap (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Journal of Pharmacy and Pharmacology (JPP): Oxford University Press (OUP)62:11, s. 1560-15680022-35732042-7158
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- Journal of Pharmacy and Pharmacology (JPP) (Sök värdpublikationen i LIBRIS)
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- Kim, Jeong-Soo
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- Alhalaweh, Amjad
- Cho, Wonkyung
- Hwang, Sung-Joo
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