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Session: Poster session II
Session starts: Thursday 24 January, 16:00

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Damiano La Zara (TU Delft)
Di Zhang (AstraZeneca)
Mike Quayle (AstraZeneca)
Gunilla Petersson (AstraZeneca)
Staffan Folestad (AstraZeneca)
Ruud van Ommen (TU Delft)

Abstract:
Active pharmaceutical ingredients (APIs) and pharmaceutical excipients are typically small solid organic particles present in the form of powders. The morphology and surface characteristics of both APIs and excipients play a crucial role in both their manufacturing and administration into the human body. Presently, nearly 40% of APIs in the pharmaceutical market have poor water solubility (i.e., below 0.1 mg mL-1), which then results in limited dissolution rate and low bioavailability into the human body. One of the best approaches to improve the bioavailability of poorly water-soluble drugs is particle size reduction, including micronization which delivers particles down to the micrometer or, in some cases, nanometer size. However, micronized particles are highly cohesive and moreover might present amorphous regions that crystallize over time in an uncontrolled manner. Therefore, there is an unmet need for commercially viable solutions to provide surface modification of pharmaceutical powders that lead to improved processability and stabilization of solid state forms (e.g., amorphous, polymorphs, hydrates) or clinical benefits, e.g., controlled release of API from dosage forms. In this work, we demonstrate the use of atomic layer deposition (ALD) as a route to modify the properties of both API (i.e., budesonide) and excipient (i.e., lactose) particles, namely dissolution rate and dispersibility. In brief, ALD enables the growth of uniform and conformal ultrathin films on complex 3D structures with exquisite thickness control at the sub-nanometer level. We study the growth of Al2O3 nanofilms in terms of uniformity and conformality on both crystalline and amorphous pharmaceutical particles of different sizes. The deposition quality strongly depends on (i) the crystal structure of the particles, (ii) the fluidization behaviour of the particles, and (iii) the chemical reactants used in the coating process. Time-of-flight secondary ion mass spectrometry and transmission electron microscopy reveal the deposition of uniform and conformal nanofilms on large crystalline particles, whereas uniform but non-conformal nanofilms are observed on small partly-amorphous particles. In-vitro dissolution tests reveal more sustained release with increasing film thickness, and in particular with improved coating uniformity. Finally, the Al2O3-coated particles exhibit considerably higher dispersibility in liquid phase, which suggests higher bioavailability than the uncoated ones.