RESUMEN
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 (Tm) 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.
RESUMEN
Pharmaceutical products serve as the cornerstone of our healthcare system. Product quality is of paramount importance to safety and efficacy of the patients. The success of pharmaceuticals has led to attempts by dubious manufacturers to gain via counterfeiting of the products, while risking the lives of the billions of patients that depend on these products. As a result, there is critical need for an analytical tool that is simple to operate, is robust and lends itself to yielding a rapid fingerprint of a pharmaceutical. In this paper we suggest use of attenuated total reflection (ATR) mid-infrared spectroscopy as a tool for rapid fingerprinting of pharmaceuticals. Antibiotics have been used as a case study to demonstrate the utility of this approach. ATR mid-infrared spectra obtained from powdered solid pharmaceutical products were classified using multivariate data analysis. A partial least-squares discriminant analysis model was developed and tested using 57 pharmaceutical products (27 antibiotics). The model was able to predict antibiotic present in pharmaceutical formulation irrespective of brand or manufacturing process with a classification accuracy of 87.3%. This indicated that the model is robust with respect to variability in pharmaceutical formulations. In addition, the brand/manufacturing company of an antibiotic could be predicted by training a principal component analysis model for specific antibiotic to a classification accuracy of 90%. The results demonstrate the utility of the proposed approach, which can be used by the appropriate authorities for checking on counterfeiting of pharmaceutical products.