Application of ATR-UV Spectroscopy for Monitoring the Crystallisation of UV Absorbing and Nonabsorbing Molecules

Abstract

In the pharmaceutical industry, controlling the crystallization process of active pharmaceutical ingredients (API) is crucial to ensure chemical quality and physical properties. Process analytical technologies (PAT) provide a large number of tools that provide information in real-time to allow mastery of the final solid chain. In this paper is described how attenuated total reflection ultraviolet (ATR-UV) spectroscopy can be used to monitor concentration. Besides its classical application to UV-absorbing molecules, it will be shown how, in principle, it may be applied to molecules that do not absorb at UV wavelengths.

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

“…Further details of PAT calibration can be found elsewhere. [59][60][61] The performance of the calibration model for prediction of solute concentration during a cooling crystallisation process can also be assessed via an off-line reference technique such as gravimetry or HPLC.…”

Precision measurement of the growth rate and mechanism of ibuprofen {001} and {011} as a function of crystallization environment

“…Unfortunately the UV/Vis depth of penetration for the ATR probe for the toluene system at the critical angle increases to infinity at 319 nm [76] and hence this technique could not be used for ibuprofen solubility measurements in toluene. In this case, the solubility was determined using gravimetric methods.…”

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

“…Where λ is the wavelength of light, θ is the ATR angle of incidence of the light relative to the crystal surface, n 1 is the refractive index of the ATR crystal and n 2 is the refractive index of the sample medium (23). Reducing the refractive index of the sample results in a shorter effective pathlength and the absorbance will be commensurately lower.…”

“…As examples, ATR-UV monitoring has been applied to support crystallization processes (23,24) and ATR-FTIR has been used for the in-line process monitoring of large-scale organic reactions (25)(26)(27). The phenomenon of ATR is based on the behavior of incident light crossing the interface between a transparent material with high refractive index, n1 (the crystal of the ATR probe) and a transparent medium with a lower refractive index, n2 (the sample) (23). A portion of the light escapes the crystal (the evanescent wave) and propagates into the sample layer at the crystal surface.…”