Application of in vitro biopharmaceutical methods in development of immediate release oral dosage forms intended for paediatric patients

Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):833-42. doi: 10.1016/j.ejpb.2013.04.015. Epub 2013 May 9.


Biopharmaceutics is routinely used in the design and development of medicines to generate science based evidence to predict in vivo performance; the application of this knowledge specifically to paediatric medicines development is yet to be explored. The aim of this review is to present the current status of available biopharmaceutical tools and tests including solubility, permeability and dissolution that may be appropriate for use in the development of immediate release oral paediatric medicines. The existing tools used in adults are discussed together with any limitations for their use within paediatric populations. The results of this review highlight several knowledge gaps in current methodologies in paediatric biopharmaceutics. The authors provide recommendations based on existing knowledge to adapt tests to better represent paediatric patient populations and also provide suggestions for future research that may lead to better tools to evaluate paediatric medicines.

Keywords: (United States) Food and Drug Administration; Absorption; BCS; Bioavailability; Biopharmaceutics; Biopharmaceutics classification system; Dissolution; EMA; European Medicines Agency; FDA; FaSSIF; Fasted state simulated intestinal fluid; FeSSIF; Fed state simulated intestinal fluid; GI; Gastrointestinal; IVIVR; In vitro in vivo relationship; MAD; Maximum absorbable dose; P-Glycoprotein; P-gp; PBPK; PK; Paediatric; Permeability; Pharmacokinetic; Physiologically based pharmacokinetic; SGF; Simulated gastric fluid; Solubility; USP; United States pharmacopoeia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Absorption
  • Administration, Oral
  • Adult
  • Biopharmaceutics / methods*
  • Biopharmaceutics / trends
  • Chemistry, Pharmaceutical / methods
  • Chemistry, Pharmaceutical / trends
  • Child
  • Computer Simulation
  • Drug Delivery Systems
  • Food-Drug Interactions
  • Humans
  • Hydrogen-Ion Concentration
  • Intestinal Absorption / drug effects
  • Pediatrics
  • Permeability
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / chemical synthesis
  • Solubility
  • Technology, Pharmaceutical / methods*
  • Technology, Pharmaceutical / trends


  • Pharmaceutical Preparations