Confocal Raman-spectroscopy: Analytical approach to solid dispersions and mapping of drugs

Purpose. To compare the physical state of a drug in a liquid with a polymer ic matrix. Methods. Solid solutions of ibuprofen in polyvinylpyrrolidone were obtained from the hot melt extrusion technique. In order to investigate the physico chemical stability, content, and homogeneity of the formulation, the tablet s produced by a subsequent calendering step were examined using confocal Ra man spectroscopy. In addition, a dimeric vinylpyrrolidone was synthesized a nd used to compare the physical state of embedding in a polymeric matrix wi th a physical solution of the active in a solvent, i.e. the dimeric vinylpy rrolidone. The spatial resolution of confocal Raman spectroscopy was used t o image the drug distribution in the final form. Results. Confocal Raman spectroscopy has been successfully used to determin e the state of ibuprofen in a solid matrix showing equivalence to a physica l solution. Moreover, the physicochemical stability of the formulation unde r stress conditions and content, as well as homogeneity of drug distributio n in the formulation matrix, has been examined with the same method, provin g the efficiency of the approach. Conclusions. Confocal Raman spectroscopy offers a new approach for the anal ytical assessment of solid dispersions both covering the physical state as well as the distribution of the drug via its spatial resolution. Moreover, it is a promising tool for observing changes in a formulation due to physic ochemical processes, e.g. recrystallisation and at the same time for locati ng the area where changes occur. Therefore, it may contribute to standard a nalytical methods to evaluate content and homogeneity.