Inhaled medicines are designed mainly to provide safe and efficacious treatment of respiratory diseases, offering the potential advantages of targeted drug delivery such as reduced onset time and increased therapeutic ratio. However, as a flipside of targeted drug delivery, drug levels in the relevant effect compartment cannot be easily assessed. In combination with technical challenges associated with aerosolizing and administering an inhaled medicine, this renders inhalation product development demanding in the regulatory aspect as well. Emerging technologies that could address some of these challenges include (i) mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modeling, which in combination with experimental techniques such as positron emission tomography could provide information on local target engagement; (ii) patient-feedback features in combination with electronic monitoring, which may improve patient adherence as well as patient handling; and (iii) controlled-release formulations and nanotechnology-based formulations with high drug load, which may expand the scope of development of compounds and targets suitable for inhalation product development.

Atomic layer deposition on pharmaceutical particles for drug delivery applications is demonstrated using assisted fluidized bed dry powder processing. Complete and conformal layering is achieved on particle sizes from the lower micron to upper nanometer range under near ambient conditions. As few as 2-14 atomic alumina layers alter particle properties: dissolution, dispersibility and heat transfer.

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, whilst maintaining the substrate particle size and morphology. Moreover, this enables nanoengineering of surfaces of pharmaceutical particles also in the dry state. Successful nano-engineeering of crystal and amorphous surfaces of pharmaceutical particles is demonstrated in this study whereby functional properties, such as dissolution and dispersability, 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 nano-size ranges to here probe both crystalline and amorphous lactose substrate surfaces (d 50 3.5 and 21 um). In addition, both water and ozone coreactants were evaluated; the latter having not been evaluated previously for pharmaceutical particles.

No abstract