Active pharmaceutical ingredients
(APIs) typically consist of solid
therapeutic particles that may acquire electrostatic charge during
milling and grinding operations. This may result in the agglomeration
of particles, thereby reducing the flowability and affecting the homogeneity
of the drug formulation. Electrostatic charge build-up may also lead
to fire explosions. To avoid charge build-up, APIs are often coated
with polymers. In this paper, atomic layer deposition (ALD) using
metal oxides such as Al2O3 and TiO2 on APIs, namely, palbociclib and pazopanib HCl, has been utilized
to demonstrate a uniform coating that results in a significant reduction
in the surface charge of the drug particles. Kelvin probe force microscopy
(KPFM) shows a 4-fold decrease in the surface contact potential of
uncoated pazopanib HCl (2.3 V) to 0.52 and 0.82 V in TiO2-and Al2O3-coated APIs, respectively. Also,
the ζ potential indicated a 4-fold decrease in the surface charge
on coating pazopanib HCl, i.e., from −32.9 mV to −7.51
and −8.51 mV in Al2O3 and TiO2, respectively. Surface morphology, thermal stability, dissolution
studies, and cytotoxicity of the drug particles after coating were
also examined. Thermal analysis indicated no change in the melting
temperature (T
m) after coating. ALD coating
was found to be uniform and conformal as observed in images obtained
from scanning electron microscopy (SEM) and scanning electron microscopy–energy-dispersive
X-ray spectroscopy (SEM–EDS). The rate of dissolution was found
to be delayed by the coating, and thus ALD offers slower drug release.
Coating APIs with TiO2 and Al2O3 did not induce
statistically significant cytotoxicity compared to the uncoated samples.
The results presented in this study demonstrate that ALD coating can
be used to reduce surface charge build-up and enhance the bulk properties
of the drug particles without affecting their physicochemical properties.