Kinetic modeling of dissolution of salicylic acid with in situ ATR UV-vis spectroscopy

Process Analytical Technologies (PAT) recommended by the Food and Drug Administration (FDA) have significantly increased during the past years in the design, control and monitoring of pharmaceutical manufacturing processes [1]. Nowadays PAT is also commonly used in Good Manufacturing Practices (GMP). Some PAT techniques employ on-line fiber-optic sensors to acquire non-destructive measurements of physical properties, kinetic information about dissolved molecule and solid fraction of particles in slurries, in real time [2]. This study uses attenuated total reflectance ultra-violet visible (ATR UV-vis) spectroscopy for kinetic modeling of the dissolution of salicylic acid in ethanol-water within a small-scale semi-batch reactor. The dissolution model, which relies on a power-law equation, can be obtained by adding aliquots of an ethanol-water mixture into a salicylic acid slurry. Near-infrared (NIR) diffuse reflectance spectroscopy is used to detect the degree of saturation and quantify the solid fraction using a classical Kubelka-Munk transformation followed by a calibration. A temperature probe is also used to monitor heat changes involved in this dissolution. [1] Fevotte G., International Journal of Pharmaceutics 241 (2002) 263-278 [2] Gemperline et al, Analytical Chemistry 76 (2004) 2575-2582