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

Molecular Pharmaceutics
Alex Avdeef

Abstract

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

References

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

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.