@article { WOS:000430368800013,
	title = {A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs},
	journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES},
	volume = {117},
	year = {2018},
	month = {MAY 30},
	pages = {98-106},
	publisher = {ELSEVIER SCIENCE BV},
	type = {Article},
	address = {PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS},
	abstract = {The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different {\textquoteleft}{\textquoteleft}stoichiometries{{\textquoteright}{\textquoteright}} (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug-reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug{\textquoteright}s absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low \% drug metabolism.},
	keywords = {BCS, BDDCS, Dissolution, Reaction limited model, Solubility, Supersaturation},
	issn = {0928-0987},
	doi = {10.1016/j.ejps.2018.02.003},
	author = {Macheras, Panos and Iliadis, Athanassios and Melagraki, Georgia}
}
