Influence of particle size on the ultraviolet spectrum of particulate-containing solutions: implications for in-situ concentration monitoring using UV/Vis fiber-optic probes.

PURPOSE: To critically evaluate the effect of submicron and micron-sized organic particulates on the ultraviolet (UV) absorption spectra of aqueous systems and assess the applicability of UV/Vis fiber-optic probes for in-situ concentration monitoring in the presence of particles of different sizes.

METHODS: UV absorbance spectra were obtained for aqueous felodipine suspensions containing a range of particle sizes (300 nm-400 μm) and suspension concentrations and for methanolic solutions of different concentrations and amorphous films of different thicknesses. Select suspensions were further characterized using nuclear magnetic resonance (NMR) experiments. Mie theory was used to provide insight into the role of particle size on scattering and absorption of UV radiation.

RESULTS: Large increases in absorbance as a function of total suspension concentration were observed for nanosuspensions but not for the other particle sizes evaluated. NMR measurements of solution concentration indicated that the observed increases in UV absorbance values for these systems were not caused by increases in the concentration of dissolved molecules, implying that nanoparticles of felodipine might absorb UV light. Mie theory-based calculations enabled reconstruction of the experimental observations and supported this hypothesis.

CONCLUSIONS: For solutions containing small (submicron) felodipine particles, UV spectra were influenced by absorption of the particles and contributions from absorption of dissolved molecules and scattering of the particles. Caution should be applied when using in situ UV/VIS-probes to monitor the amount of dissolved material during dissolution, in particular when small particles are present (e.g. dissolution of nanoparticulate formulations) or generated (e.g. precipitation of supersaturated solutions) in the dissolution medium.