Evaluation of crystallization behavior on the surface of nifedipine solid dispersion powder using inverse gas chromatography.

PURPOSE: To investigate crystallization behavior on the surface of amorphous solid dispersion powder using inverse gas chromatography (IGC) and to predict the physical stability at temperatures below the glass transition temperature (T (g)).

METHODS

Amorphous solid dispersion powder was prepared by melt-quenching of a mixture of crystalline nifedipine and polyvinylpyrrolidon (PVP) K-30. IGC was conducted by injecting undecane (probe gas) and methane (reference gas) repeatedly to the solid dispersion at temperatures below T (g). Surface crystallization was evaluated by the retention volume change of undecane based on the observation that the surface of the solid dispersion with crystallized nifedipine gives an increased retention volume.

RESULTS

On applying the retention volume change to the Hancock-Sharp equation, surface crystallization was found to follow a two-dimensional growth of nuclei mechanism. Estimation of the crystallization rates at temperatures far below T (g) using the Avrami-Erofeev equation and Arrhenius equation showed that, to maintain its quality for at least three years, the solid dispersion should be stored at -20°C (T (g) - 65°C).

CONCLUSIONS

IGC can be used to evaluate crystallization behavior on the surface of a solid dispersion powder, and, unlike traditional techniques, can also predict the stability of the solid dispersion based on the surface crystallization behavior.