title: Study of pH-dependent solubility of organic bases. Revisit of Henderson-Hasselbalch relationship.
abstract: In this paper the pH-equilibrium solubility profiles of six organic drugs are presented. The equilibrium solubility values were determined using the saturation shake-flask and the Chasing Equilibrium Solubility (CheqSol) methods. Results obtained by the two methods are in good agreement. The aim of the present work was to study the validity of the Henderson-Hasselbalch (HH) relationship in the case of structurally diverse weak bases. The significance of pH control and the effect of the salt form (e.g., fumarate) was also investigated. In the case of monoprotic bases, namely papaverine, promethazine, propafenone and ticlopidine the experimental solubility data precisely follow the HH equation until the limit of salt solubility. The common ion effect on salt solubility was found to be significant at low pHs. Deviation from the HH equation in the case of dibasic quetiapine hydrogen fumarate and the ampholyte desvenlafaxine hydrogen fumarate can be easily interpreted with the formation of different salt compositions. It was concluded that precise pH control is essential in shake-flask solubility measurements. It is also critical that the pK(a) value and the intrinsic solubility are accurately determined when the HH relationship is used to predict the pH-dependent aqueous solubility of drugs.
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, H-1092 Budapest, Hogyes E. u. 9., Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Völgyi
authors.forename: Edit
authors.initials: E
authors.lastname: Baka
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Box
authors.forename: John E A
authors.initials: JE
authors.lastname: Comer
authors.forename: Krisztina
authors.initials: K
authors.lastname: Takács-Novák
mesh_terms: D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility
chemical_list: D007477:Ions; D004364:Pharmaceutical Preparations