D. Grant, M. Mehdizadeh, A. Chow
1984
Citations
6
Influential Citations
328
Citations
Quality indicators
Journal
International Journal of Pharmaceutics
Abstract
Abstract The aqueous solubilities of acetaminophen, adipic acid and the parabens (methyl, ethyl, propyl and butyl p -hydroxybenzoate) have been measured over a temperature span of at least 50°C. Both the van't Hoff plots of t x sat 2 against 1/T and the Hildebrand plots of ln x sat 2 against ln T are non-linear, where x sat 2 is the mole fraction solubility at an absolute temperature, T. The pharmaceutical significance and the physicochemical origin of such non-linear behaviour are discussed, since the pharmaceutical literature indicates it is by no means uncommon and may give rise to errors and misconceptions. When more than 5 data points covering a relatively wide range of temperatures are available, it is recommended that the data be treated by multiple regression analysis according to the equation: ln(solubility) == (—a/R)(1/T) + (b/R) ln T + c, where a, b and c are constant for the solute-solvent system and R is the gas constant. From a, b and c, the apparent thermodynamic parameters for the solution process may be calculated, e.g. ΔH == a + bT, and ΔC p = b. This treatment has been applied to the parabens series in particular which is shown not to be as homologous as formerly supposed. The van't Hoff plot (b = 0) and the Hildebrand plot (a = 0, b = ΔS) are special cases of the recommended equation applicable only over a relatively narrow temperature span. The addition of further adjustable constants into the recommended equation is considered to be unnecessary at the present time.