PMID: 11899112Mar 20, 2002Paper

Physicochemical profiling (solubility, permeability and charge state)

Current Topics in Medicinal Chemistry
A Avdeef

Abstract

About 30% of drug candidate molecules are rejected due to pharmacokinetic-related failures. When poor pharmaceutical properties are discovered in development, the costs of bringing a potent but poorly absorbable molecule to a product stage by "formulation" can become very high. Fast and reliable in vitro prediction strategies are needed to filter out problematic molecules at the earliest stages of discovery. This review will consider recent developments in physicochemical profiling used to identify candidate molecules with physical properties related to good oral absorption. Poor solubility and poor permeability account for many PK failures. FDA's Biopharmaceutics Classification System (BCS) is an attempt to rationalize the critical components related to oral absorption. The core idea in the BCS is an in vitro transport model, centrally embracing permeability and solubility, with qualifications related to pH and dissolution. The objective of the BCS is to predict in vivo performance of drug products from in vitro measurements of permeability and solubility. In principle, the framework of the BCS could serve the interests of the earliest stages of discovery research. The BCS can be rationalized by considering Fick's first law, a...Continue Reading

Citations

Oct 21, 2006·Pharmaceutical Research·Stefanie BendelsAlex Avdeef
Jan 25, 2007·Pharmaceutical Research·Alex AvdeefManfred Kansy
Aug 19, 2007·Pharmaceutical Research·Lana X GarmireC Anthony Hunt
Nov 6, 2010·Pharmaceutical Research·Xiangli LiuAlfred Fahr
Mar 5, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Marival BermejoVirginia Merino
Sep 3, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Nasim HeshmatiGert Fricker
Feb 26, 2004·Free Radical Biology & Medicine·Kuresh A YoudimN Joan Abbott
Mar 22, 2005·International Journal of Pharmaceutics·Kouki ObataYosinori Aso
May 17, 2003·European Journal of Medicinal Chemistry·Arturo BattagliaAntonella Riva
Apr 25, 2003·International Journal of Pharmaceutics·Kiyohiko SuganoYoshinori Aso
Oct 21, 2003·Journal of Pharmacological and Toxicological Methods·Kin-Kai HwangNancy E Martin
Dec 4, 2003·Drug Discovery Today·Kuresh A YoudimN Joan Abbott
Dec 8, 2004·Drug Discovery Today·Ho-Ming PangShelley Coldiron
Mar 8, 2005·Drug Discovery Today·Praveen V Balimane, Saeho Chong
Jun 27, 2003·Current Opinion in Chemical Biology·Li Di, Edward H Kerns
Jul 23, 2008·Journal of the American Chemical Society·Adekunle I ElegbedeSanku Mallik
Jan 24, 2013·Molecular Pharmaceutics·Ivan S KrylovCharles E McKenna
Oct 30, 2010·Nature Protocols·Luís M MagalhãesJosé L F C Lima
Dec 22, 2009·SAR and QSAR in Environmental Research·D T Manallack
May 29, 2013·The Journal of General Physiology·Radda RusinovaOlaf S Andersen
Mar 18, 2010·Assay and Drug Development Technologies·Helgi I Ingólfsson, Olaf S Andersen
Sep 29, 2007·Science·Klaus MüllerFrançois Diederich
Apr 7, 2010·Antimicrobial Agents and Chemotherapy·Michael Zhuo WangKarl A Werbovetz
Jun 4, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard W AhnThomas V O'Halloran
May 6, 2009·The AAPS Journal·Eric D Agdeppa, Mary E Spilker
Aug 19, 2007·Expert Opinion on Drug Metabolism & Toxicology·Florian NigschSilvia Miret
Feb 21, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Mohammad S AlavijehAlan M Palmer
Jan 1, 2009·Journal of Liquid Chromatography & Related Technologies·Bo Zheng, Lyndon M West
Apr 6, 2006·The AAPS Journal·Praveen V BalimaneSaeho Chong
Feb 25, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Juan P JoubertDavid D N'Da
Mar 7, 2014·Journal of Pharmaceutical and Biomedical Analysis·P WiczlingR Kaliszan
Oct 29, 2013·Journal of Chromatographic Science·Simona Codruţa CobzacCostel Sârbu
Sep 30, 2008·Pharmaceutical Development and Technology·Monica C ChuongJames W Ayres
Apr 8, 2016·International Journal for Parasitology. Drugs and Drug Resistance·Bracken F RobertsDebopam Chakrabarti
Feb 9, 2016·Journal of Pharmaceutical and Biomedical Analysis·Baiwei Lin, Joseph H Pease
May 28, 2011·Drug Development and Industrial Pharmacy·Venugopal P MarasanapalleBhaskara R Jasti
Jun 1, 2010·Expert Opinion on Drug Delivery·Pallavi Bassi, Gurpreet Kaur
Apr 20, 2004·Drug Development and Industrial Pharmacy·Kouki ObataYoshinori Aso
Nov 28, 2006·Expert Opinion on Drug Metabolism & Toxicology·Bernard FallerLaszlo Urban
Jun 29, 2011·Drug Development and Industrial Pharmacy·Kalle SigfridssonKristina Ohlson

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