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 rates investigated. Whilst the increased solubility of PAS in the presence of its major breakdown product m-aminophenol (MAP) dictated that equilibrium solubilities were unable to be determined, apparent solubilities at 10 degrees C after 1 h equilibration were obtained. The order of decreasing solubility and intrinsic dissolution rate for metallic salts of PAS was potassium > sodium > calcium (low hydrate) > calcium (trihydrate) = magnesium. When data for PAS and its ammonium and ethanolamine salts were included, a direct relationship between log solubility (C-s) and log dissolution rate (IDR) was observed. Since the apparent solubility of the potassium salt was only qualitatively known, by applying this solubility-dissolution rate relationship its solubility was predicted to be 2.5 M/l(-1) at 10 degrees C using the regression line 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 sulphate salts of PAS could not be estimated since these salts reverted during dissolution to form PAS.