Physicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble Pharmaceutical Compounds
✍ Scribed by Karl J. Box; Gergely Völgyi; Rebeca Ruiz; John E. Comer; Krisztina Takács-Novák; Elisabeth Bosch; Clara Ràfols; Martí Rosés
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- German
- Weight
- 181 KB
- Volume
- 90
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
A mixture of cosolvents is described that significantly improves the solubility of most pharmaceutical compounds. The mixture consists of equal volumes of MeOH, 1,4-dioxane, and MeCN, thereby containing polar and nonpolar solvents, and is referred to as MDM (from MeOH, dioxane, and MeCN). MDM is mixed with H 2 O until the required composition is reached. The utility of this system is that it enables analytical measurements to be performed on a wide range of compounds where measurements would be impaired in aqueous solution. We present the physicochemical characteristics of MDM/H 2 O mixtures (density, dielectric constant, p s K w ) and the principles of pK a measurement in this solvent/H 2 O mixture. We also present pK a values in H 2 O of several drug compounds determined from values measured in MDM/H 2 O mixtures.