Impact of the counterion on the solubility and physicochemical properties of salts of carboxylic acid drugs

Drug Development and Industrial Pharmacy
Sarah E DavidBarbara R Conway

Abstract

Salt formation is a widely used approach to improve the physicochemical and solid state properties of an active pharmaceutical ingredient. In order to better understand the relationships between the active drug, the selected counterion and the resultant salt form, crystalline salts were formed using four different carboxylic acid drugs and a closely related series of amine counterions. Thirty-six related crystalline salts were prepared, characterized and the relationship between solubility and dissolution behaviour and other properties of the salt and the counterion studied. Salts of four model acid drugs, gemfibrozil, flurbiprofen, ibuprofen and etodolac were prepared using the counterions butylamine, hexylamine, octylamine, benzylamine, cyclohexylamine, tert-butylamine, 2-amino-2-methylpropan-1-ol, 2-amino-2-methylpropan-1,3-diol and tris(hydroxymethyl)aminomethane. Salt formation was confirmed, the salts were characterized and their corresponding solubilities determined and rationalized with respect to the counterions' properties. The properties of the salt highly dependent on the nature of the counterion and, although there is considerable variation, some general conclusion can be drawn. For the alkyl amines series, increas...Continue Reading

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Citations

Oct 22, 2013·International Journal of Pharmaceutics·Enes SupukBarbara R Conway
Apr 23, 2013·Drug Development and Industrial Pharmacy·Dong Hoon OhHan-Gon Choi
Oct 25, 2014·Drug Development and Industrial Pharmacy·Shashank JainSenshang Lin
Sep 12, 2012·Drug Development and Industrial Pharmacy·Kwan Hyung Cho, Han-Gon Choi
Nov 24, 2012·International Journal of Pharmaceutics·Nirmal MarasiniJong Oh Kim
Mar 17, 2015·International Journal of Pharmaceutics·Kofi Asare-AddoBarbara R Conway
Oct 25, 2014·Journal of Toxicology and Environmental Health. Part a·Duck Soo LimByung-Mu Lee
Jul 28, 2016·Colloids and Surfaces. B, Biointerfaces·Adeola O AdebisiKofi Asare-Addo
Jun 3, 2017·Organic & Biomolecular Chemistry·Changdong ShaoYanghui Zhang
Jan 30, 2019·Journal of Drug Targeting·Laura Tiozzo FasioloPaola Russo
Feb 7, 2013·Pharmacological Reviews·Hywel D WilliamsChristopher J H Porter
Nov 30, 2019·Natural Product Research·Shravankumar Kankala, Ravinder Vadde
Oct 2, 2019·Pharmaceutics·Sawittree SahakijpijarnRobert O Williams
Mar 4, 2021·Pharmaceutical Development and Technology·Afrooz HamidehMansoor A Khan
Jul 17, 2021·International Journal of Pharmaceutics·Kalle SigfridssonSara Lindblom
Jun 17, 2020·Analytical Chemistry·Jernej ŠtukeljSami Svanbäck
Feb 12, 2019·Journal of Chemical Information and Modeling·Victoria T LimDavid L Mobley

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