Evaluating pediatric and adult simulated fluids solubility: Abraham solvation parameters and multivariate analysis

Mariana Guimarães, Martin Kuentz, Maria Vertzoni, Nikoletta Fotaki

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)

Abstract

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.

Original languageEnglish
Pages (from-to)1889-1896
Number of pages8
JournalPharmaceutical Research
Volume38
Issue number11
Early online date25 Oct 2021
DOIs
Publication statusPublished - 30 Nov 2021

Keywords

  • Abraham solvation parameters
  • Biorelevant
  • Multivariate analysis
  • Pediatric
  • Solubility

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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