title: In vitro oral drug permeation models: the importance of taking physiological and physico-chemical factors into consideration.
abstract: The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico-chemical factors that may have an influence on these techniques are critically reviewed. The shortcomings identified for some of the in vitro techniques are discussed in conjunction with novel ways to improve and thereby overcome some challenges. Expert opinion: Although conventional in vitro methods and theories are used as basic guidelines to predict drug absorption, critical evaluations have identified some shortcomings. Advancements in technology have made it possible to investigate and understand the role of physiological and physico-chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment.
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Ruan
authors.initials: R
authors.lastname: Joubert
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Johan Dewald
authors.initials: JD
authors.lastname: Steyn
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Hendrik Jacobus
authors.initials: HJ
authors.lastname: Heystek
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Jan Harm
authors.initials: JH
authors.lastname: Steenekamp
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Jan Lourens
authors.initials: JL
authors.lastname: Du Preez
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Josias Hendrik
authors.initials: JH
authors.lastname: Hamman
mesh_terms: D000284:Administration, Oral; D016503:Drug Delivery Systems; D055808:Drug Discovery; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations
keywords: In vitro model; drug permeation; pharmacokinetics; physico-chemical factors; physiological factors