Common ion effect on solubility and dissolution rate of the sodium salt of an organic acid

Abstract

The solubility and the dissolution rate of the sodium salt of an acidic drug (REV 3164; 7-chloro-5-propyl-1H,4H-[1,2,4]triazolo[4,3-alpha]quinoxaline-1,4-dione) decreased by the effect of common ion present in aqueous media. The solubility of the sodium salt of REV 3164 in a buffered medium was much lower than that in an unbuffered medium. Also, the presence of NaCl decreased its solubility in water. The apparent solubility product (K'sp) of the salt, however, did not remain constant when the concentration of NaCl was changed. A decrease in K'sp value with the increase in NaCl concentration was observed; for example, the K'sp values at 0 and 1 M NaCl were 7.84 X 10(-4) and 3.94 X 10(-4) M2, respectively. Even when corrected for the effect of ionic strength, the solubility product decreased. This decrease in the solubility product in the presence of NaCl indicated a decrease in the degree of self-association (increase in activity coefficient) of the drug in aqueous media.

Multivariate Data Analysis of Factors Affecting the In Vitro Dissolution Rate and the Apparent Solubility for a Model Basic Drug Substance in Aqueous Media

“…This factor was therefore included in the multivariate data analysis since little information was found in the literature for the apparent in vitro dissolution rate experiments using pure drug substances, without focusing on the so-called common ion effect (83,84). It has been established by others that the ionic strength is a significant factor for dissolution testing of a felodipin formulation (aprotic drug substance) in phosphate buffer (47).…”

Enhanced dissolution of the substrate d,l‐2‐amino‐Δ2‐thiazoline‐4‐carboxylic acid and enzymatic production of l‐cysteine at high concentrations

“…Considering that d,l-ATC has a carboxyl group [1], its solubility was expected to depend on the solution pH [9][10][11]. Considering that d,l-ATC has a carboxyl group [1], its solubility was expected to depend on the solution pH [9][10][11].…”

“…For a high product yield, the substrate d,l-ATC should be dissolved at a high concentration level in an aqueous solution. Considering that d,l-ATC has a carboxyl group [1], its solubility was expected to depend on the solution pH [9][10][11]. Besides, it is known that enzymes engaged in the conversion of d,l-ATC to l-cysteine are stable in high ionic strengths of salt solutions [3].…”

“…Methods for increasing the solubility of compounds by controlling the physicochemical environment (e.g. pH) have been developed [9][10][11][12]. The pH control is one of most common methods to be employed in aqueous media [13].…”

Solubility of Pharmaceutical Solids

“…Generally, the salt solubility plateau is reached when the difference between the solubility of the unionized and the ionized species is about 4 log units for acids and 3 log units for bases (Avdeef, 2003(Avdeef, , 2004. However, there are several exceptions (Serajuddin and Jarowski, 1985a,b;Serajuddin et al, 1987).…”