Does Polyvinylpyrrolidone Improve the Chemical Stability of Cilazapril in Solid State?

In this study a solid dispersion and a physical mixture of cilazapril (CIL) with a biopolymer - polyvinylpyrrolidone (PVP) as a carrier were prepared so as to investigate the effect of PVP on the stability of CIL. CIL is unstable in solid state and decomposes rapidly under humid conditions. It requires stabilization to ensure safety of its use. The studied CIL/PVP formulations were prepared by milling and evaporation technique. Their identity was confirmed by FT-IR method. The stability of CIL in the CIL/PVP formulations was assessed by forced ageing test under isothermic conditions using RP-HPLC. The influence of temperature (experimental conditions: RH 76.4% and T = 70, 75, 80, 85, and 90 oC) and the effect of relative humidity (experimental conditions: RH 25.0%, 50.9%, 60.9%, 66.5%, 76.4%, T = 90 °C) on the rate of CIL degradation were examined. It was established that the process of CIL decay in the studied forms followed first-order kinetics with the formation of one degradation product - cilazaprilat. The degradation rate constant of this reaction was lower than that for pure CIL. The energy of activation of the CIL degradation in the presence of PVP was higher than that of pure CIL. Furthermore, CIL incorporated into PVP exhibited lower sensitivity to moisture. Based on these data PVP was considered as a potential stabilizing substance for CIL-containing dosage forms.