Daniel Mufson

pH-Solubility Profiles of Organic Bases and Their Hydrochloride Salts

Knowledge of comparative solubility profiles of a base and its hydrochloride salt is important in selecting one form over the other for dosage form design. The studies with two model bases, namely, tiaramide and papaverine, showed that, except during phase transition from a base to a salt or vice versa, the pH-solubility profiles are identical whether a base or a salt are used. The solubilities were determined by equilibration after addition of hydrochloric acid or sodium hydroxide solutions to suspensions of bases and salts. With the addition of hydrochloric acid solution, the pH values of the suspensions of tiaramide and papaverine dropped to 5.0 ± 0.1 and 4.0 ± 0.1, respectively, and then remained constant until supersaturated solutions were formed. After nucleation of supersaturated solutions with the addition of hydrochloride salt or the reduction of temperature, the precipitation of hydrochloride salt occurred. The solubilities of salts decreased at low pH due to common ion effect. The Kosp values, however, did not remain constant and the solubility profiles showed positive deviations from the theoretical ones. These may be due to a possible self-association and the resultant difference between the solubilities and activities of the compounds in solutions. The reported differences between the solubilities of bases and their respective hydrochloride salts at a particular pH and the lack of common ion effects on the solubilities and dissolution rates of bases are explained.

Effect of thermal history on the glassy state of indapamide

The effects of thermal history, e.g. cooling rate, annealing, etc., on the thermal behaviour of indapamide glass were determined by differential scanning calorimetry (DSC). The glass was prepared by heating indapamide crystals (m.p. 162 °C) to 180 °C., and then cooling the melt to room temperature. The glass transition temperature (Tg) of the material was 98 °C. An endotherm, due to thermal relaxation of the glass, was observed in the DSC thermogram when indapamide glass was prepared by slow cooling or was annealed isothermally at a temperature below Tg. Such enthalpy relaxation may be observed during ageing of pharmaceutical glasses and might influence their physicochemical properties.