Physical stability of l-ascorbic acid amorphous solid dispersions in different polymers: A study of polymer crystallization inhibitor properties

The effects of different polymer types on inhibiting the crystallization of ascorbic acid (VitC) from amorphous solid dispersions at various temperatures and relative humidities (RHs) were studied. Polymer properties (ability to form hydrogen bonds with VitC, hygroscopicity, and glass transition temperature (Tg)) were correlated to their crystallization inhibitor performance. Solid dispersions of VitC with different pectins, polyvinylpyrrolidone (PVP), and polyacrylic acid (PAA) were formed from lyophilized solutions. Crystallinity, VitC-polymer interactions, hygroscopicity, and Tg were determined using X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), moisture sorption isotherm, and differential scanning calorimetry (DSC) methods, respectively. XRPD amorphous VitC could not be formed by lyophilization in the absence of a polymer, nor in PAA dispersions, but could be formed in pectin and PVP dispersions. The VitC-pectin and PVP dispersions remained amorphous when stored at low RHs, but some crystallization occurred within one week at high RHs. Evidence of hydrogen bonding between VitC and both pectins and PVP, but not PAA, was found in FTIR spectra, and correlated better with physical stability than the Tg. The hygroscopicity of the polymer also influenced the stability of the amorphous VitC solid dispersions. A ranking of the polymer crystallization inhibitor properties was: PVP > pectin with lower degree of esterification (DE) > pectin with higher DE > > PAA.