Effects of formulation, light and relative humidity on solid-state stability of nifedipine spray microspheres

Abstract

The solid-state of nifedipine spray dried microspheres was investigated to determine the effect of the ratio between combined polymers (Eudragit RS100 and PVP K30), the inlet air temperature, the microsphere size, the drug-polymer ratio, the light intensity and the addition of UV absorbers (curcumin, curcumin crude extract, tartrazine and sunset yellow) and antioxidant (sodium bisulfite) on the photostability of nifedipine microspheres and the effect of relative humidity on the chemical and physical stabilities of nifedipine microspheres. The high pressure liquid chromatographic method was used for nifedipine analysis. The degradation was shown to follow the first-order kinetics. The increase of PVP K30 in formula, inlet air temperature and drug-polymer ratio increased the photo degradation rate constant (p<0.05). The small particle size as measured by the image analyzer was found to significantly increase the degradation rate constant (p<0.05). The light intensity increment also increased the degradation rate constant of nifedipine microspheres (p<0.05). The addition of curcumin gave the highest protection power among other UV absorbers and antioxidant studied, both in solution and solid-state of nifedipine. The relative humidity did not influence the chemical stability of nifedipine microspheres. The moisture uptake of nifedipine microspheres increased with the relative humidity and the PVP K30 content. The critical relative humidities were determined from the relative humidity at which the water uptake rate was zero. On exposrure to light, relative humidity and temperature in the ambient atmosphere, no degradation was found in the stabilized nifedipine microspheres by curcumin. There was no difference between the Higuchi dissolution rate constants of nifedipine microspheres with and without curcumin.