Stability challenges in drug discovery

Chemistry & Biodiversity
Li Di, Edward H Kerns

Abstract

Stability is one of the most important properties of drug candidates. Instable compounds can lead to false positive high-throughput screening (HTS) hits, incorrect bioassay results, erroneous structure-activity relationships (SAR), low oral bioavailability, drug withdrawal, toxic reactions from degradation products, and difficult formulation development. Screening of stability has been implemented early in drug discovery to identify labile chemotypes and guide structural modification. The most commonly applied stability studies in drug discovery are stability-pH profile, stability in gastrointestinal fluids, stability in bioassay media, excipient compatibility, and prodrug screening. The strategy enhances the quality of drug development candidates and reduces the risks.

References

Aug 1, 1984·Journal of Pharmaceutical Sciences·L ChafetzJ Philip
Dec 1, 1994·Journal of Pharmaceutical Sciences·R D Skwierczynski, K A Connors
Aug 1, 1993·The Journal of Pharmacy and Pharmacology·M S Islam, M M Narurkar
Apr 2, 1998·Journal of Pharmaceutical Sciences·C Goolcharran, R T Borchardt
Jul 31, 2001·Analytical Biochemistry·D E Epps, B M Taylor
Feb 21, 2002·Pharmaceutical Development and Technology·Kenneth C WatermanChristopher J Roberts
Jun 18, 2002·Pharmaceutical Development and Technology·Kenneth C WatermanHai Wang
Nov 16, 2002·International Journal of Pharmaceutics·Nina NiSamuel H Yalkowsky
Feb 5, 2003·Drug Discovery Today·Gilbert M Rishton
Apr 30, 2004·Journal of Medicinal Chemistry·Peter EttmayerBernard Testa
Nov 24, 2004·Drug Development and Industrial Pharmacy·Pei Yang, Fraser Macdonald
Jan 6, 2005·Journal of the American Chemical Society·Jeffrey R HuthPhilip J Hajduk
Mar 22, 2005·International Journal of Pharmaceutics·Kenneth C Waterman, Roger C Adami
Oct 20, 2005·Journal of Biomolecular Screening·Li DiSusan L Petusky
Jul 25, 2006·International Journal of Pharmaceutics·Yutaka HirakuraSatoshi Kitamura
Nov 23, 2006·Journal of Pharmaceutical and Biomedical Analysis·Yong-Xue GuoHong-Bin Xiao
Feb 16, 2007·Journal of Pharmaceutical and Biomedical Analysis·Ebenezer B Asafu-AdjayeDonna A Volpe
Jun 23, 2007·International Journal of Pharmaceutics·D DesaiM Bolgar
Jul 14, 2007·Advanced Drug Delivery Reviews·Valentino J Stella, Kwame W Nti-Addae
Aug 21, 2007·Journal of Pharmaceutical and Biomedical Analysis·Sushila BhattaraiColin C Duke
Apr 12, 2008·International Journal of Pharmaceutics·Louis Philippe MassicotteMircea Alexandru Mateescu
May 20, 2008·International Journal of Pharmaceutics·V Hayden Thomas, Maryanne Naath
Nov 11, 2008·Current Drug Metabolism·Li Di, Edward H Kerns

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Citations

May 3, 2013·Journal of Computer-aided Molecular Design·Y Jane TsengAnang A Shelat
Jul 18, 2014·Journal of Computer-aided Molecular Design·Zhihong LiuJun Xu
Aug 20, 2011·Biomedical Chromatography : BMC·Marcello LocatelliFrancesco Epifano
Mar 10, 2015·International Journal of Pharmaceutics·Anne Marie V Schou-PedersenSteen Honoré Hansen
Jun 25, 2016·International Journal of Pharmaceutics·Sophie GeboersPatrick Augustijns
Oct 27, 2018·Biopharmaceutics & Drug Disposition·Sangwoo RyuLi Di
Feb 25, 2021·Biopharmaceutics & Drug Disposition·Jonathan J NovakLi Di
Feb 16, 2019·Journal of Chemical Information and Modeling·Xiuming LiJun Xu

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