Surface nanocoating of high drug-loading spray-dried amorphous solid dispersions by atomic layer coating: Excellent...

Physical instability remains a major concern with amorphous solid dispersions (ASDs). In addition to bulk crystallization inhibition, another potential strategy to improve the physical stability of ASDs is surface engineering. However, coating processes are extremely challenging for ASD microparticles. Herein, we describe for the first time the application of atomic layer coating (ALC), a solvent-free technique, to deposit a pinhole-free, ultra-thin film of aluminum oxide onto the surface of spray-dried ASD particles containing high drug loadings of ezetimibe with hydroxypropyl methylcellulose acetate succinate. ALC affords excellent control over the thickness, uniformity and conformality of the coating at the atomic scale. The freshly prepared coated ASD powders exhibited less agglomeration, a lower hygroscopicity, as well as improved wettability, flowability and compressibility compared to the uncoated samples. Under accelerated storage conditions, crystallization was detected in the uncoated 50% and 70% drug loading ASDs after only a few days, whereas the coated samples showed no evidence of physical instability for two years. Consequently, there was a dramatic decrease in the drug release from the uncoated ASDs during storage, while little change was observed for the coated samples. Using ALC for surface nanocoating of ASD paves the way for the development of higher drug loading ASD without compromising physical stability, thereby reducing the pill burden.