Fourier Transform Infrared mapping to determine the distribution of active ingredients in pharmaceutical formulations

A basic problem in pharmaceutical manufacturing is that a relatively simple formulation can produce widely varying therapeutic performance depending upon how the ingredients are distributed in the final matrix. Many methods have been employed to study the distribution of different components in a tablet. Traditional spectroscopic techniques analyze the sample in bulk and determine an average composition across the entire sample. Conventional spectroscopy cannot directly determine the spatial distribution of the components in the final product. To accomplish this, use of chemical maps and images have become increasingly important during the past few years. The objective of this study is to evaluate vibrational maps based on Fourier Transform Infrared (FT-IR) spectroscopic as a tool to assess drug product homogeneity in tablets.; Variables, such as spectral and spatial resolution, which may impact the performance of maps based on FT-IR, were evaluated. After establishing optimal parameters, FT-IR mapping was performed on different positions, chosen arbitrarily on the surface of the tablet. Measurements were carried out for commercial tablets and reference laboratory-manufactured tablets, containing pure Active Pharmaceutical Ingredient (API). The spatial distribution of API was determined based on the variation or contrast in pixel intensity, which in turn is provided by the intrinsic vibrational signature of the constituent in the tablet. Moreover, histograms of the maps were generated and statistical procedures were used as a measure of the homogeneity of the distribution.; Chemical images were generated by using the most unique peak of the API spectrum and as principal component (PC) scores. The application of multivariate (Chemometrics) analysis had the aim to demonstrate if the univariate approach provided a clear description of the chemical features of the sample. Similarity between the images obtained by the two methods of analysis was established. FT-IR mapping has turned out to be an important method to gain information concerning microscopic characterization of samples.