Transmission Raman spectroscopy for non-destructive analysis of pharmaceuticals

Abstract

Direct transmission Raman measurements for analysis of pharmaceuticals in capsules are advantageous since they can be used to determine active pharmaceutical ingredient (API) concentrations in a non-destructive manner and with much less fluorescence background interference from the capsules themselves compared to conventional back-scattering measurements. If a single calibration model such as developed from spectra simply collected in glass vials could be used to determine API concentrations of samples contained in capsules of different colors rather than constructing individual models for each capsule color, the utility of transmission measurements would be further enhanced. In Chapter 1, to evaluate the feasibility, transmission Raman spectra of binary mixtures of ambroxol and lactose were collected in a glass vial and a partial least squares (PLS) model for the determination of ambroxol concentration was developed. Then, the model was directly applied to determine ambroxol concentrations of samples contained in capsules of 4 different colors (blue, green, white and yellow). Although the prediction performance was slightly degraded when the samples were placed in blue or green capsules, due to the presence of weak fluorescence, accurate determination of ambroxol was generally achieved in all cases. The prediction accuracy was also investigated when the thickness of the capsule was varied. In Chapter 2, the variation of accuracy for the determination of ambroxol concentration, when different sizes of sample particle are used for Raman measurement, has been investigated. It was based on the possibility that the particle size could influence on the resulting Raman feature as well as accuracy of measurement. For this purpose, 4 different sizes (over 150, 150-100, 100-50, under-50 ��m) of ambroxol samples (ambroxol concentration from 9.0 to 15.0 wt%) were prepared and then Raman spectra were collected by varying the packing thickness from 1 to 7 mm with an increment of 1 mm. Using each dataset, PLS was performed to determine the concentration of ambroxol and the resulting accuracies were evaluated in relation with the particle size and packing thickness.