Analytical control of pharmaceutical production steps by near infrared reflectance spectroscopy

A method for the analytical control of different pharmaceutical production steps involving various types of sample (blended products, cores and coated tablets) is proposed. The measurements are made by using a near infrared (NIR) diffuse reflectance spectrophotometer furnished with a fibre-optic module that enables expeditious, flexible analyses with no sample manipulation.Calibration for the active principle in the pharmaceutical is done by applying partial least-squares regression to first-derivative spectra over the wavelength range 1100-2200nm. Various spectral pretreatments for minimizing spectral scattering were tested. All samples studied were analysed by using a single calibration including spectra of laboratory samples in order to expand the concentration range spanned by the production samples, as well as samples obtained in different steps of the production process in order to include its variability sources (variations in origin of raw materials, particle size distribution, compactness, granulation, etc.). Production samples for inclusion in the calibration set were chosen by principal component analysis. The partial least squares model based on first-derivative spectra provided a relative standard error of prediction lower than 1% for production samples. Copyright (C) 1999 Elsevier Science B.V.