Solubility-pH profiles of a free base and its salt: sibutramine as a case study

Abstract

In the present study the solubility-pH profiles of sibutramine free base and its hydrochloride salt were determined in the pH range between 2.0 and 9.5 by means of the recommended shake-flask method, and the solids collected were dried and studied by X-ray diffraction in order to elucidate their free base or salt structure. Above pH_max (or Gibbs pK_a) the solid collected was always identified as free base, whatever the sibutramine species (free base or hydrochloride salt) initially solved. However, in the pH range below pH_max different solids were isolated depending on the buffers employed.