Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility
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Compound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility.
Solubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37°C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media.
For six of the seven compounds investigated, solubility fell outside an 80–125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II).
Developmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.
KEY WORDSbiopharmaceutics biorelevant pediatric solubility
Biopharmaceutics classification systems
Fasted-state simulated gastric fluid
Fasted-state simulated intestinal fluid
Fed-state simulated gastric fluid
Fed-state simulated intestinal fluid
Free fatty acids
In vitro–in vivo correlations
Pediatric biopharmaceutics classification systems
United States Food and Drug Administration
ACKNOWLEDGMENTS AND DISCLOSURES
This work was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC). The authors would also like to express their gratitude to Sarah Cordery for her guidance within the laboratory and Fotios Baxevanis for his assistance with the analysis.
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