A comparative study on the performance of inert and functionalized spheres coated with solid dispersions made of two structurally related antifungal drugs

Fluid bed coating offers potential advantages as a formulation platform for amorphous solid dispersions (ASDs) of poorly soluble drugs, being a one-step manufacturing process which could reduce therisk of phase separation associated with multiple step manufacturing approaches. However, the impact of the physicochemical nature of carrier spheres on the properties and drug release from the ASDshas not been studied in detail. In this work, tartaric acid (TAP) and microcrystalline cellulose (CEL) spheres were chosen as examples of functional and inert beads, respectively. Two structurallyrelated triazole antifungals, itraconazole (ITR) and posaconazole (POS), were chosen as model drugs. Solid-state investigations revealed that the fluidized bed process result in both types of spheresuniformly coated with ITR and POS ASDs based on Eudragit® L100-55 (EUD). A single glass transition temperature (Tg) was determined for each of the ASDs. Infrared studies suggested the presence of aweak interaction between POS and TAP, which translated into premature release of POS from the POS/EUD ASD coated TAP spheres in FaSSGF and subsequently lower POS cumulative release in comparison tothe ASD coated on CEL beads. High resolution investigations of morphological and compositional changes during dissolution, using scanning electron microscopy and atomic force microscopy coupled withnanoscale thermal investigation, revealed that crystallization of the drug from the ASDs was induced during dissolution when TAP spheres were used as carriers. In contrast, ASDs coated on CELunderwent phase separation and drug-rich nanospecies were formed in the matrix due to the solubility gap between the drug and EUD in FaSSIF. This study demonstrates that properties of carrier for theASD fundamentally affect the drug release properties and the proper selection of such beads is critical to ensure product quality.