Solid dispersion has shown to be a promising formulation strategy to enhance dissolution for hydrophobic drugs. However, solid dispersions are often thermodynamically unstable, there is a continuous interest in studying their stabilities. In this study, attenuated total reflectance Fourier transform infrared (ATR-FTIR) was used to compare the amount of crystalline nifedipine formed in different formula of poly(ethylene glycol) (PEG)-nifedipine solid dispersions when exposed at various relative humidities (RHs) for 2 h at 40°C. The ratio of the crystalline nifedipine band and an internal reference band in the out of plane δ(C-H) region has been used to indicate the relative degree of drug crystallisation in a sample. A band ratio of ∼0.05 and 0.5 was respectively indicative of a fully amorphous or crystallised drug in the formula. Results show that increasing the RH generally increases the amount of crystalline nifedipine. Formulations with low (5%, w/w) nifedipine concentration in higher molecular weight PEG were found to be better at resisting crystallisation. Deliquescence of the 10% nifedipine in PEG 4000 was observed at 77% and 100% RH with a reduction in crystalline nifedipine. All 5% (w/w) nifedipine samples were stable at RH below 77%. Crystallisation of nifedipine occurred at all RH when drug loading was increased to 10% (w/w).
Keywords: FT-IR; bioavailability; drug loading; humidity; infrared spectroscopy; molecular dispersion; polymer; polymorphism; quantitative analysis; univariate analysis.
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.