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Bioavailability of ...
Bioavailability of indomethacin-saccharin cocrystals
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- Jung, Min-Sook (författare)
- Chungnam National University
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- Kim, Jeong-Soo (författare)
- Chungnam National University
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- Kim, Min-Soo (författare)
- Chungnam National University
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- Alhalaweh, Amjad (författare)
- Luleå tekniska universitet,Medicinsk vetenskap
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- Cho, Wonkyung (författare)
- Chungnam National University
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- Hwang, Sung-Joo (författare)
- Chungnam National University
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- Velaga, Sitaram (författare)
- Luleå tekniska universitet,Medicinsk vetenskap
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(creator_code:org_t)
- 2010-10-11
- 2010
- Engelska.
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 62:11, s. 1560-1568
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Annan hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Other Health Sciences (hsv//eng)
Nyckelord
- bioavailability
- cocrystals
- dissolution
- indomethacin
- salts
- Health Science
- Hälsovetenskap
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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