Using Raman spectroscopy in tablet moisture surface analysis: Tablet surface markers

Abstract

A method was developed to monitor the hydration of a tablet surface using chemical functional groups able to bind atmospheric water through H-bonding. In this study, generic oral dissolving loratadine tablets were used. These tablets have relatively high mannitol and lactose concentrations. Both mannitol and lactose have C–OH alcohol functional groups, several of which are potentially available for H-bonding with atmospheric water. The Raman intensity of the alcohol functional groups decreases upon hydration. This observation can be used to indirectly monitor water adsorbed to tablet surfaces at the alcohol sites. The hydration assay is based on the change in the Raman peak intensity of the alcohol C–OH stretching at 875.5 cm −1. Consequently the decrease in the Raman intensity of this vibration can be used to monitor water adsorption. The Raman measurement of tablet surface water was compared to the direct moisture measurement method using a microbalance. The Raman spectroscopy is used to monitor the water that is specifically bound to the C–OH alcohol functional groups available for hydration. The microbalance was used to monitor the tablets’ weight change during water adsorption and desorption. The distribution of the ratio of the Raman intensity of C–OH peak at 875.5 cm −1 divided by the intensity of loratadine's C–Cl peak at 712.6 cm −1 was experimentally determined to be a Gaussian distribution with a mean of 3.22 ± 0.277. Raman analysis indicates that there is both tightly and loosely bound water at the tablet surface. This can be a useful technique with regard to inspecting and controlling the tablet drying process.