(298d) Surface Engineering of Lactose Particles By Atomic Layer Deposition for Modified Release
In this work, we study the effect of co-reactants, namely H2O and O3, on the Al2O3 growth on two kinds of lactose particles (i.e., fully crystalline lactose and crystalline lactose with micronization-induced amorphous surfaces) and evaluate the dissolution behaviour. The ALD process is carried out at ambient conditions in a fluidized bed reactor for a low number of cycles (i.e., from 4 to 14) using trimethylaluminum (TMA) as a metal precursor. Time-of-flight secondary ion mass spectrometry and Transmission Electron Microscopy (TEM) show that TMA/O3 ALD on crystalline lactose particles offers greatly improved control over the coating uniformity and conformality compared to TMA/H2O ALD. In fact, by causing severe agglomeration of the particles, water deteriorates the fluidization quality and thus the homogeneity of the coating process. In-vitro dissolution tests reveal more sustained release for the O3-based process than for the H2O-based one, thus underlining the benefit of O3 in providing uniform and conformal coatings. However, little to no difference between TMA/O3 and TMA/H2O ALD is observed on lactose particles with amorphous surfaces. In fact, such amorphous surfaces firstly are inherently inhomogenous across the particles and secondly present micropores, as suggested by BET measurements. This inevitably leads to non-conformal films regardless of the co-reactant and moreover results in both surface and subsurface growth.
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 Di Zhang, Mike J. Quayle, Gunilla Petersson, J. Ruud van Ommen and Staffan Folestad, Atomic scale surface engineering of micro- to nano-sized pharmaceutical particles for drug delivery applications, Nanoscale, 2017, 9, 11410-11417