title: Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Developmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Anil R
authors.initials: AR
authors.lastname: Maharaj
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Edginton
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. n.fotaki@bath.ac.uk.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Fotaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D000465:Algorithms; D001647:Bile Acids and Salts / Q000737:chemistry; D001702:Biopharmaceutics; D001826:Body Fluids / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D041981:Gastrointestinal Tract / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007408:Intestinal Absorption; D009994:Osmolar Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012995:Solubility; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D004364:Pharmaceutical Preparations
keywords: biopharmaceutics; biorelevant; pediatric; solubility