Atomic Layer Deposition Coating on the Surface of Active Pharmaceutical Ingredients to Reduce Surface Charge Build-Up

Abstract

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.

Atomic Layer Coating to Inhibit Surface Crystallization of Amorphous Pharmaceutical Powders

“…The ERL/PVPVA system contained no hydroxyl groups, yet the onset of crystallization was delayed from 2 to 6 weeks at the 40 °C/43% RH storage condition for the ALC-coated particles (Figure ). The authors note that the ALC process has been successfully performed on substrates having other functional groups, such as amines …”

“…The authors note that the ALC process has been successfully performed on substrates having other functional groups, such as amines. 66 It was similarly of interest to determine if anchoring sites (hydroxyl functional groups) present on the polymer would protect a drug without anchoring sites from crystallization. A delay in crystallization onset was observed for the ERL/ HPMCAS system from 2 to 3 weeks at the 40 °C/75% RH storage condition and from 2 weeks to more than 48 weeks at the 40 °C/43% RH storage condition (Figure 9).…”

Effect of Atomic Layer Coating on the Stability of Solid Myoglobin Formulations

“…La Zara et al showed that budesonide coated by aluminum oxide, titanium oxide, or silicon oxide had significantly prolonged drug release and did not show cytotoxicity in a human epithelial alveolar A549 cell line. , The aluminum oxide coating enabled higher drug loading and cell viability in comparison to titanium oxide and silicon oxide coatings . For palbociclib and pazopanib HCl powders, ALC coating reduced surface charge build-up and enhanced bulk material properties . Furthermore, the ALC-coatings were shown to modify the surface properties of budesonide, increase hydrophilicity, and improve powder properties without causing structural changes or cytotoxicity .…”

“…19 For palbociclib and pazopanib HCl powders, ALC coating reduced surface charge build-up and enhanced bulk material properties. 20 Furthermore, the ALC-coatings were shown to modify the surface properties of budesonide, increase hydrophilicity, and improve powder properties without causing structural changes or cytotoxicity. 21 More recently, ALC coating has been applied to powders containing amorphous solid dispersions (ASD) of poorly water-soluble drugs, providing inhibition of drug crystallization in the ASD during storage for up to 2 years.…”