Preparation of Free-Flowing Spray-Dried Amorphous Composites Using Neusilin.

A highly porous additive, Neusilin, with high adsorption capability is investigated to improve bulk properties, hence processability of spray-dried amorphous solid dispersions (ASDs). Griseofulvin (GF) is applied as a model BCS class 2 drug in ASDs. Two grades of Neusilin, US2 (coarser) and UFL2 (finer), were used as additives to produce spray-dried amorphous composite (AC) powders, and their performance was compared with the resulting ASDs without added Neusilin. The resulting AC powders that included Neusilin had greatly enhanced flowability (flow function coefficient (FFC) > 10) comparable to larger particles (100 μm) yet had finer particle size (< 50 μm), hence retaining the advantage of fast dissolution rate of finer sizes. Dissolution results demonstrated that achieved GF supersaturation for AC powders with Neusilin was as high as 3 times that of crystalline GF concentration and was achieved within 30 min. In addition, 80% of drug was released within 4 min. The flowability improvement for AC powders with Neusilin was more significant as compared to spray-dried ASDs without Neusilin. Thus, the role of Neusilin in flowability improvement was evident, considering that spray-dried AC with Neusilin UFL2 has higher FFC than ASDs having a similar size. Lastly, the AC powders retained a fully amorphous state of GF after 3-month ambient storage. The overall results conveyed that the improved flowability and dissolution rate could outweigh the loss of drug loading resulted by addition of Neusilin.