Atomic and Molecular Layer Deposition for Controlled Drug Delivery

Abstract

The majority of pharmaceutical products is made of solid powders. The morphology and surface characteristics of drug particles affect both their bulk behaviour, e.g., flowability, dispersibility and tabletability, in the manufacturing process of dosage forms as well as their bioavailability upon administration into the human body. For instance, in pulmonary drug delivery, particles with an aerodynamic diameter <5 µm are required to reach the action sites of the lungs. Surface modification provides the means to tailor crucial functionalities of pharmaceutical particles, such as dissolution, wettability, flowability and dispersibility, based on the desired formulation design. Atomic layer deposition (ALD) and molecular layer deposition (MLD) are gas-phase film technologies that enable atomic-level control over surface properties through the fabrication of nanoscale films on individual particles, which impact the powder performance. The benefits of ALD and MLD for pharmaceuticals compared to existing surface modification techniques include (i) gas-phase and fully solventless nature of the process, (ii) wide range of process conditions, including low temperature and atmospheric pressure, (iii) control over the amount of deposited material and film thickness in the sub-nanometer and low-nanometer range, (iv) high drug loadings due to the nanoscale films, (v) uniform and conformal films, crucial for tailored functional properties. Moreover, the possibility to carry out ALD and MLD in fluidized bed reactors offers scalable processing and manufacturing of bulk quantities of nano-engineered powders, relevant for pharmaceutical applications. This thesis deals with the development of ALD and MLD processes on excipient and drug particles, especially for pulmonary delivery, to control their release and enhance their dispersibility and flowability.