Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API...

Molecular dynamics of pure nifedipine and its solid dispersions with modified carbohydrates as well as the crystallization kinetics of active pharmaceutical ingredient (API) above and below the glass transition temperature were studied in detail by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction method. It was found that the activation barrier of crystallization increases in molecular dispersions composed of acetylated disaccharides, whereas it slightly decreases in those consisting of modified monocarbohydrates for the experiments carried out above the glass transition temperature. As shown by molecular dynamics simulations it can be related to the strength, character, and structure of intermolecular interactions between API and saccharides, which vary dependently on the excipient. Long-term physical stability studies showed that, in solid dispersions consisting of acetylated maltose and acetylated sucrose, the crystallization of nifedipine is dramatically slowed down, although it is still observable for a low concentration of excipients. With increasing content of modified carbohydrates, the crystallization of API becomes completely suppressed. This is most likely due to additional barriers relating to the intermolecular interactions and diffusion of nifedipine that must be overcome to trigger the crystallization process.