Zsolt Zsigmond

Raman microscopic evaluation of technology dependent structural differences in tablets containing imipramine model drug

Raman imaging method was used to characterize the effect of different manufacturing technologies on properties of the produced tablets, such as compound distribution, polymorphism, strength, and estimated active pharmaceutical ingredient (API) content. The obtained chemical maps were evaluated based on their visual appearance and on the statistical properties of the component scores obtained by direct classical least squares (DCLS) modelling. It is demonstrated that changes in the distribution of the API and excipients can be detected with chemical imaging and these differences are in close relationship with the applied granulation method and with the mechanical properties of the analyzed tablet. It is also shown that the chemical images used for characterizing the component distribution can also be processed for obtaining a cautious estimation to the mass fractions of the components.

Testing the performance of pure spectrum resolution from Raman hyperspectral images of differently manufactured pharmaceutical tablets.

Chemical imaging is a rapidly emerging analytical method in pharmaceutical technology. Due to the numerous chemometric solutions available, characterization of pharmaceutical samples with unknown components present has also become possible. This study compares the performance of current state-of-the-art curve resolution methods (multivariate curve resolution-alternating least squares, positive matrix factorization, simplex identification via split augmented Lagrangian and self-modelling mixture analysis) in the estimation of pure component spectra from Raman maps of differently manufactured pharmaceutical tablets. The batches of different technologies differ in the homogeneity level of the active ingredient, thus, the curve resolution methods are tested under different conditions. An empirical approach is shown to determine the number of components present in a sample. The chemometric algorithms are compared regarding the number of detected components, the quality of the resolved spectra and the accuracy of scores (spectral concentrations) compared to those calculated with classical least squares, using the true pure component (reference) spectra. It is demonstrated that using appropriate multivariate methods, Raman chemical imaging can be a useful tool in the non-invasive characterization of unknown (e.g. illegal or counterfeit) pharmaceutical products.

OPLC combined with NIR spectroscopy - A novel technique for pharmaceutical analysis

We report a new combination of overpressured-layer chromatography (OPLC) with near-infrared (NIR) spectroscopy for pharmaceutical analysis. Different pharmaceutical preparations containing caffeine, paracetamol, and acetylsalicylic acid as model compounds were separated by OPLC. The band density in the solid phase after OPLC was suitable for study of the separated components directly on the layer by NIR spectroscopy. We have demonstrated the applicability of rapid OPLC separation combined with UV densitometry and NIR spectroscopy for both qualitative and quantitative analysis. This OPLC—UV—NIR technique is thus suitable for rapid, nondestructive investigation of multicomponent pharmaceutical preparations and enables a different type of pharmaceutical analysis, e.g. starting-material tests, in-process control, end-product control, stability testing, etc. Another benefit of this newly developed combination of rapid off-line techniques is the possibility of simultaneous collection of qualitative and quantitative chromatographic and spectral information.