Abstract: Valuable information concerning stability of compounds can be obtained
by using different media (water, hydrochloric acid or sodium hydroxide) for dissolution of
active pharmaceutical substances. Furthermore, additional knowledge is gained by performing experiments at different temperatures. This research paper deals with the stability of
amlodipine besylate and bisoprolol fumarate in different media at different temperatures,
whereby certain conclusions are drawn. For stability assessment, chemical kinetics approach was used, and constant rate (k), half-time (t1/2) and activation energy (Ea) were used for
prediction of compound stability degree. The stability of amlodipine besylate and bisoprolol fumarate were tested, both separately and in mixture, in water and in 0.01M HCl. All the
investigated solutions were treated at two temperatures 25° and 70°C at the following time
intervals: 0, 1 h, 24 h, 48 h and 72 h. Hydrophilic Interaction Liquid Chromatography –
HILIC method, previously developed and validated, was used. On the basis of obtained
results it was concluded that amlodipine-besylate was more stable in water than in acid
medium, more stable in mixture rather than individually and more stable at lower temperatures.
This was confirmed by the obtained values of monitored parameters: amlodipine
besylate Ea = 30.68 kJ mol-1, k (25 °C) = 0.000333 mM h-1, k (70 °C) = 0.00169 mM h-1;
amlodipine besylate in mixture Ea = 42,414 kJ mol-1, k (25 °C) = 1.27·10-4 mM h-1,
k (70 °C) = 0.0012 mM h-1. Based on the obtained approximate Ea value for bisoprolol
fumarate in acid (59 kJ mol-1) and in water (56 kJ mol-1), bisoprolol fumarate showed
excellent stability against the media in which it was studied. On the other hand, the temperature had a significant effect on the stability of bisoprolol fumarate. These results provide
the relevant information about the stability of the tested active substances, and may be of
importance during the development of an appropriate pharmaceutical product. A bigger
influence on the stability of bisoprolol fumarate had a temperature effect.
