Role of Surface Characteristics of Mannitol in Crystallization of Fenofibrate During Spray Drying.

NanoCrySP™ is a novel spray-drying-based technology for the generation of nanocrystalline solid dispersions of active pharmaceutical ingredients embedded in the matrix of small molecule excipients. Active pharmaceutical ingredient first appears as an amorphous phase, which transforms to crystalline phase during its passage in the drying chamber. Mannitol acts as a crystallization inducer for the intermediate amorphous phase by primary heterogeneous nucleation. Heteronucleation is a surface-assisted phenomenon and surface characteristics of mannitol were hypothesized to play important role. This study investigates the role of surface characteristics of mannitol on crystallization kinetics of amorphous fenofibrate. Crystallization kinetics of amorphous fenofibrate was assessed on 2 surfaces of mannitol having different porosity, roughness, and polarity. Fenofibrate showed faster crystallization in the presence of rougher surface (t < 1 min) compared with smooth surface (t = 49.28 min). This was attributed to higher porosity (75%) and surface polarity (~1.25-fold) of rough surface as compared with smooth surface. Polar nature provided primitive sites for faster crystallization of amorphous fenofibrate. These findings can be utilized for generating crystalline solid dispersions using spray drying in the presence of mannitol. The crystalline solid dispersions can be used for the development of oral solid dosage forms.