Molecular Mobility and Crystal Growth in Amorphous Binary Drug Delivery Systems: Effects of Low-Concentration...

Polymer additives have been widely reported to affect the crystallization of amorphous drugs, while the underlying mechanism is poorly understood. The present study aims to investigate the relationship between the crystal growth and the molecular mobility of amorphous nifedipine (NIF) in the presence and absence of low-concentration poly(ethylene oxide) (PEO). The addition of 3% w/w PEO yields approximately a 5-fold increase in the crystal growth rate of NIF in the glassy matrix and a 10-fold increase in the supercooled liquid. Broadband dielectric spectroscopy is performed to investigate the molecular mobility of amorphous pure NIF system and NIF doped with low-concentration PEO. With 3% w/w PEO, the structural relaxation time τ_α of amorphous NIF significantly decreases, indicating an increase in the global molecular mobility. However, the increase of the molecular mobility is insufficient to explain the 5- to 10-fold increase of the crystal growth rate at the same τ_α scale. Moreover, we compare the accelerating effect of PEO in NIF-PEO systems to other PEO-doped systems. The accelerating effect of low-concentration PEO on the crystal growth of amorphous drugs is found to be independent of the Flory-Huggins interaction, T_g of the drug, or the increase of the global molecular mobility. These findings suggest that an in-depth understanding regarding the effects of polymer additives on the crystallization of drugs should consider the localized mobility of the host molecules near the crystal-liquid interface.