Solubility vs Dissolution in Physiological Bicarbonate Buffer

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dc.catalogadorgjm
dc.contributor.authorClaussen, Felix
dc.contributor.authorAl-Gousous, Jozef
dc.contributor.authorSalehi, Niloufar
dc.contributor.authorGarcía Alcalde, Mauricio Andrés
dc.contributor.authorAmidon, Gordon L.
dc.contributor.authorLangguth, Peter
dc.date.accessioned2025-01-02T15:56:02Z
dc.date.available2025-01-02T15:56:02Z
dc.date.issued2024
dc.description.abstractBackground: Phosphate buffer is often used as a replacement for the physiological bicarbonate buffer in pharmaceutical dissolution testing, although there are some discrepancies in their properties making it complicated to extrapolate dissolution results in phosphate to the in vivo situation. This study aims to characterize these discrepancies regarding solubility and dissolution behavior of ionizable compounds. Methods: The dissolution of an ibuprofen powder with a known particle size distribution was simulated in silico and verified experimentally in vitro at two different doses and in two different buffers (5 mM pH 6.8 bicarbonate and phosphate). Results: The results showed that there is a solubility vs. dissolution mismatch in the two buffers. This was accurately predicted by the in-house simulations based on the reversible non-equilibrium (RNE) and the Mooney models. Conclusions: The results can be explained by the existence of a relatively large gap between the initial surface pH of the drug and the bulk pH at saturation in bicarbonate but not in phosphate, which is caused by not all the interfacial reactions reaching equilibrium in bicarbonate prior to bulk saturation. This means that slurry pH measurements, while providing surface pH estimates for buffers like phosphate, are poor indicators of surface pH in the intestinal bicarbonate buffer. In addition, it showcases the importance of accounting for the H2CO3-CO2 interconversion kinetics to achieve good predictions of intestinal drug dissolution.
dc.fechaingreso.objetodigital2025-01-02
dc.format.extent9 páginas
dc.fuente.origenSCOPUS
dc.identifier.doi10.1007/s11095-024-03702-5
dc.identifier.issn1573-904X
dc.identifier.scopusidSCOPUS_ID:85191970794
dc.identifier.urihttps://doi.org/10.1007/s11095-024-03702-5
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89444
dc.information.autorucEscuela de Química; García Alcalde, Mauricio Andrés; S/I; 181066
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final945
dc.pagina.inicio937
dc.publisherSpringer
dc.revistaPharmaceutical Research
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 Attribution 4.0 International Deed
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBicarbonate buffer
dc.subjectDissolution
dc.subjectIbuprofen
dc.subjectMass transport modelling
dc.subjectPhosphate buffer
dc.subject.ddc510
dc.subject.deweyMatemática física y químicaes_ES
dc.titleSolubility vs Dissolution in Physiological Bicarbonate Buffer
dc.typeartículo
dc.volumen41
sipa.codpersvinculados181066
sipa.trazabilidadSCOPUS;2024-05-12
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