Evaluating pediatric and adult simulated fluids solubility. Abraham solvation parameters and multivariate analysis
Lade...
Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2021
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Pharmaceutical Research
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
38
Ausgabe / Nummer
Seiten / Dauer
1889-1896
Patentnummer
Verlag / Herausgebende Institution
Springer
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Purpose: To understand drug solubilization as a function of age and identify drugs at risk of altered drug solubility in pediatric patients. To assess the discrimination ability of the Abraham solvation parameters and age-related changes in simulated media composition to predict in vitro drug solubility differences between pediatric and adult gastrointestinal conditions by multivariate data analysis.
Methods: Differences between drug solubility in pediatric and adult biorelevant media were expressed as a % pediatric-to-adult ratio [Sp/Sa (%)]. Solubility ratios of fourteen poorly water-soluble drugs (2 amphoteric; 4 weak acids; 4 weak bases; 4 neutral compounds) were used in the analysis. Partial Least Squares Regression was based on Abraham solvation parameters and age-related changes in simulated gastrointestinal fluids, as well as their interactions, to predict the pediatric-to-adult solubility ratio.
Results: The use of Abraham solvation parameters was useful as a theory-informed set of molecular predictors of drug solubility changes between pediatric and adult simulated gastrointestinal fluids. Our findings suggest that the molecular solvation environment in the fasted gastric state was similar in the pediatric age-groups studied, which led to fewer differences in the pediatric-to-adult solubility ratio. In the intestinal fasted and fed state, there was a high relative contribution of the physiologically relevant surfactants to the alteration of drug solubility in the pediatric simulated conditions compared to the adult ones, which confirms the importance of an age-appropriate composition in biorelevant media.
Conclusion: Statistical models based on Abraham solvation parameters were applied mostly to better understand drug solubility differences in adult and pediatric biorelevant media.
Schlagwörter
Abraham solvation parameters, Biorelevant, Multivariate analysis, Pediatric, Solubility
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
0724-8741
1573-904X
1573-904X
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Hybrid
Lizenz
Zitation
Guimaraes, M., Kuentz, M., Vertzoni, M., & Fotaki, N. (2021). Evaluating pediatric and adult simulated fluids solubility. Abraham solvation parameters and multivariate analysis. Pharmaceutical Research, 38, 1889–1896. https://doi.org/10.1007/s11095-021-03123-8