Nanoengineering of Crystal and Amorphous Surfaces of Pharmaceutical Particles for Biomedical Applications

Abstract

The morphology, size, and surface properties of pharmaceutical particles form an essential role in the therapeutic performance of active pharmaceutical ingredients (APIs) and excipients as constituents in various drug delivery systems and clinical applications. Recent advances in methods for surface modification, however, rely heavily on liquid-phase-based modification processes and afford limited control over the thickness and conformality of the coating. Atomic layer deposition (ALD), on the other hand, enables the formation of conformal nanoscale films on complex structures with thickness control on the molecular level, while maintaining the substrate particle size and morphology. Moreover, this enables nanoengineering of surfaces of pharmaceutical particles also in the dry state. Successful nanoengineeering of crystal and amorphous surfaces of pharmaceutical particles is demonstrated in this study whereby functional properties, such as dissolution and dispersibility, were tailored for drug delivery applications. This expands on our initial work on ALD of alumina on pharmaceutical particles within the lower micro- to higher nanosize ranges to here probe both crystalline and amorphous lactose substrate surfaces (d₅₀ = 3.5 and 21 μm). In addition, both water and ozone coreactants were evaluated, the latter having not been evaluated previously for pharmaceutical particles. The deposition process is carried out at ambient conditions in a fluidized bed reactor for a low number of cycles (i.e., from 4 to 14). Improved dissolution and extended release were achieved by the ALD nanoengineering of both crystalline and amorphous surfaces. This novel concept opens up exciting opportunities to produce more complex materials and structures using temperature- and moisture-sensitive drugs, e.g., targeting and drug delivery opportunities, as well as delivering new functionalities for novel applications in the pharmaceutical, medical, biological, and advanced materials fields. The prospects for advancing inhaled drug delivery are exemplified by the ALD surface nanoengineering concept.