Disproportionation of Pharmaceutical Salts: pHmax and Phase-Solubility/pH Variance.

Molecular Pharmaceutics
Alex Avdeef


A multiphasic mass action equilibrium model is used to show that the critical pH in the acid-base disproportionation of a solid salt into its corresponding solid free-base form in aqueous suspensions, widely known as "pHmax", is incompletely interpreted. It is shown that the traditional thermodynamic model does not predict the invariance of pH and solubility during the salt-to-free-base conversion process in an alkalimetric titration. Rather, the conversion entails a range of pH and solubility values, depending on the amount of added excess salt above that needed to form a saturated solution. A more precise definition is proposed for pHmax (pH at the maximum solubility of a eutectic mixture), and three new terms are introduced: pHmin (pH at the minimum solubility of the eutectic mixture), pHδ (disproportionation invariant pH within the eutectic, i.e., the equilibrium pH of a spontaneously disproportionating salt slurry), and pHγ (Gibbs pH at which disproportionation yields equimolar amounts of excess salt and excess free-base solids within the eutectic). Two test compounds with reported multiple salts and the free-base solubility values were selected to illustrate the expanded concepts, the bases WR-122455 and RPR-127963. Also,...Continue Reading


Feb 1, 1979·Journal of Pharmaceutical Sciences·J B Bogardus, R K Blackwood
Aug 1, 1985·Journal of Pharmaceutical Sciences·B D Anderson, R A Conradi
Dec 1, 1972·Journal of Pharmaceutical Sciences·S F Kramer, G L Flynn
May 1, 1966·Biochemical Pharmacology·G Zografi, I Zarenda
Jun 1, 1995·Journal of Pharmaceutical Sciences·Y SurakitbanharnS H Yalkowsky
May 1, 1995·Journal of Pharmaceutical Sciences·Z WangB Chu
Sep 16, 1999·International Journal of Pharmaceutics·W H Streng
Jul 13, 2002·Journal of Pharmaceutical Sciences·Zeren WangWilliam J Lambert
Mar 1, 1953·Journal of the American Pharmaceutical Association·T HIGUCHIL W BUSSE
Nov 1, 1964·Journal of Pharmaceutical Sciences·L W DITTERTD R REESE
Sep 2, 2005·Journal of Pharmaceutical Sciences·Shoufeng LiAbu T M Serajuddin
Aug 26, 2006·Pharmaceutical Research·Ramprakash GovindarajanRaj Suryanarayanan
Apr 25, 2007·Journal of Pharmaceutical Sciences·Simon N BlackRon J Roberts
Apr 25, 2007·Journal of Pharmaceutical Sciences·Sherif I Farag Badawy, Munir A Hussain
Jul 10, 2007·Advanced Drug Delivery Reviews·Abu T M Serajuddin
Jul 24, 2007·Advanced Drug Delivery Reviews·Alex Avdeef
Jun 10, 2009·Pharmaceutical Research·Peter Guerrieri, Lynne S Taylor
Jul 20, 1930·The Journal of General Physiology·J H Northrop, M Kunitz
Dec 8, 2009·Journal of Pharmaceutical Sciences·Peter GuerrieriLynne S Taylor
Mar 5, 2011·Journal of Pharmaceutical Sciences·Gregory A StephensonTimothy A Woods
Mar 1, 1985·Pharmaceutical Research·A T Serajuddin, D Mufson
Apr 16, 2015·Pharmaceutical Research·Yi-Ling HsiehLynne S Taylor
Jul 28, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Aneta PobudkowskaAlex Avdeef
Feb 7, 2017·International Journal of Pharmaceutics·Naveen K Thakral, Ron C Kelly
Apr 11, 2017·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alex Avdeef
May 18, 2018·International Journal of Pharmaceutics·Mitulkumar A PatelLynne S Taylor
Aug 26, 2018·Journal of Pharmaceutical and Biomedical Analysis·Taiga Uekusa, Kiyohiko Sugano
Mar 28, 2019·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Olivera S MarkovićAlex Avdeef
Nov 23, 2020·Drug Discovery Today·Sonali S Bharate

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