Evaluation of NIR and Raman spectroscopies for the quality analytical control of a solid pharmaceutical formulation with three active ingredients.

Abstract

The manufacture of pharmaceutical products is one of the most regulated industrial sectors due to the importance of its products on human health. These regulations require a high number of physical and chemical determinations. These last are commonly performed by using chromatographic techniques coupled to different detectors, even though the use of spectroscopic techniques is growing.This study was aimed to evaluate the performance of a NIR and Raman spectroscopy methodologies for the quantitative determination of three active ingredients (APIs) with different concentrations (6.8%w/w, 26.3%w/w and 26.3%w/w) in a solid pharmaceutical product. Calibration models and prediction results were compared in terms of precision and prediction accuracy with those obtained through HPLC reference method. Different spectral pretreatments have been used to reduce the spectral variability associated with the physical characteristics of samples. Standard Normal Variate (SNV) and 2nd derivative (2D) were used as spectral treatments to correct scattering effect in NIR spectra. The best pretreatments for Raman were a baseline correction and a normalization. Each model was developed and evaluated with full subsets cross-validation and external validation sample set. For each technique, the best model was selected based on conventional criteria (R2, RMSEPCV).Results show highly predictive models based on NIR and Raman spectroscopy with root mean square error of prediction values between 0.26%w/w and 2.60%w/w depending on the active ingredient and the analytical technique. The methodologies have been applied for an adequate determination of the uniformity of the dosing units of two commercial lots. In addition, Raman spectroscopy application allowed the detection of an inappropriate distribution of active ingredients in pharmaceutical products.