Stability of API as a Key Parameter for New Formulations Development - A Case Study of Rosuvastatin Calcium

Abstract

This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.