Towards a covering aerospray method for quantitative analyses of pharmaceutical tablets using surface-enhanced Raman chemical imaging (SER-CI)

In recent years, the use of SERS-CI in pharmaceutical sciences has increased in order to study the distribution of low-dose compounds in solid dosage forms [1]. This technique allows to improve the sensitivity of conventional Raman microscopy and to reduce significantly the image acquisition time by exalting the signal information.
However, the applications of SERS-CI in the pharmaceutical field remain limited, especially due to the difficulty of obtaining a homogeneous deposit of metallic nanoparticles on the sample surface. Generally, the covering method used on the tablet is a drop casting deposition due to its simplicity and rapidity of implementation. Despite the colloidal solution deposit is not fully controlled. The inhomogeneous covering is the result of the “coffee-ring” effect that concentrates the nanoparticles at the edges of the droplet [2]. This implies remarkable variations of the SERS analyte signal’s intensity at different places.
For a more reproducible and homogeneous coating, an aerospray method using a homemade apparatus was developed (Figure 1). The device is composed with a pair of coaxial tubes, the colloidal solution is pulled through the inner tube from a syringe pump and the outer tube is connected to a source of high pressure gas. Nitrogen, used as a nebulizing gas, creates a flow of small droplets of nanoparticles that are nearly dry when they hit the sample surface. The aerospray device is easy to implement and the entire surface of the tablet is covered by the SERS substrate in a homogeneous way. By using this covering method, the potential of SERS-CI is improved and making it a suitable technique for quantitative analyses of low drug concentrations or impurities in pharmaceutical tablets.