DISSOLUTION KINETICS AND SOLUBILITIES OF P-AMINOSALICYLIC ACID AND ITS SALTS

A series of metal and amine salts of p-aminosalicylic acid (PAS) were synthesized and their water solubilities and intrinsic dissolution rat es investigated. Whilst the increased solubility of PAS in the presenc e of its major breakdown product m-aminophenol (MAP) dictated that equ ilibrium solubilities were unable to be determined, apparent solubilit ies at 10 degrees C after 1 h equilibration were obtained. The order o f decreasing solubility and intrinsic dissolution rate for metallic sa lts of PAS was potassium > sodium > calcium (low hydrate) > calcium (t rihydrate) = magnesium. When data for PAS and its ammonium and ethanol amine salts were included, a direct relationship between log solubilit y (C-s) and log dissolution rate (IDR) was observed. Since the apparen t solubility of the potassium salt was only qualitatively known, by ap plying this solubility-dissolution rate relationship its solubility wa s predicted to be 2.5 M/l(-1) at 10 degrees C using the regression lin e log IDR = 1.06 log C-s - 0.166 (r = 0.9931, n = 7). The relationship could not be used where a phase change at the solid-liquid interface occurred. Thus, the solubilities of the tosylate, mesylate and sulphat e salts of PAS could not be estimated since these salts reverted durin g dissolution to form PAS.