Abstract
Purpose. To compare the physical state of a drug in a liquid with a polymeric matrix.
Methods. Solid solutions of ibuprofen in polyvinylpyrrolidone were obtained from the hot melt extrusion technique. In order to investigate the physicochemical stability, content, and homogeneity of the formulation, the tablets produced by a subsequent calendering step were examined using confocal Raman spectroscopy. In addition, a dimeric vinylpyrrolidone was synthesized and used to compare the physical state of embedding in a polymeric matrix with a physical solution of the active in a solvent, i.e. the dimeric vinylpyrrolidone. The spatial resolution of confocal Raman spectroscopy was used to image the drug distribution in the final form.
Results. Confocal Raman spectroscopy has been successfully used to determine the state of ibuprofen in a solid matrix showing equivalence to a physical solution. Moreover, the physicochemical stability of the formulation under stress conditions and content, as well as homogeneity of drug distribution in the formulation matrix, has been examined with the same method, proving the efficiency of the approach.
Conclusions. Confocal Raman spectroscopy offers a new approach for the analytical 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 physicochemical processes, e.g. recrystallisation and at the same time for locating the area where changes occur. Therefore, it may contribute to standard analytical methods to evaluate content and homogeneity.
Similar content being viewed by others
REFERENCES
R. L. Gupta, R. Kumar, and A. K. Singla. Enhanced dissolution and absorption of trimethoprim from coprecipitates with polyethylene glycols and polyvinyl-pyrrolidone. Drug Dev. Ind. Pharm. 17:463–468 (1991).
J. L. Ford. The current status of solid dispersions. Pharm. Acta Helv. 61:69–88 (1986).
K. Nakamichi, H. Yasuura, H. Kukui, M. Oka, S. Izumi, T. Andou, N. Shimizu, and K. Ushimaru. New preparation method of solid dispersion by twin screw extruder. Pharm. Tech. Jpn. 12:715–729 (1996).
J. Breitenbach, G. Berndl, J. Neumann, J. Rosenberg, D. Simon, and J. Zeidler. Solid dispersions by an integrated melt extrusion system. Proceed. Int. Symp. Contr. Rel. Soc. 25:804–805 (1998).
B. C. Hancok, S. L. Shamblin, and G. Zografi. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperature. Pharm. Res. 12:799–805 (1995).
N. M. Najib, M. Salem, and A. Sheikh. Release of ibuprofen from polyethylene glycol solid dispersions: equilibrium solubility approach. Drug Dev. Ind. Pharm. 13:2263–2275 (1987).
H. E. Junginger and M. Wedler. Thermal stability of mefruside-polyvinylpyrrolidone solid dispersions. Pharm. Res. 3:41–44 (1986).
L. S. Taylor and G. Zografi. The quantitative analysis of crystallinity using FT-Raman spectroscopy. Pharm. Res. 15:755–761 (1998).
B. A. Bolton and P. Prasad. Laser Raman investigation of drug-polymer conjugates: sulfathiazole-povidone co-precipitates. J. Pharm. Sci. 73:1849–1851 (1984).
T. Wilson. Confocal Raman microscopy, Academic Press, London, 1990.
J. W. Breitenbach. Dimeres hydriertes Vinylpyrrolidon. Monatsh. d. Chem. 82:833–834 (1951).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Breitenbach, J., Schrof, W. & Neumann, J. Confocal Raman-Spectroscopy: Analytical Approach to Solid Dispersions and Mapping of Drugs. Pharm Res 16, 1109–1113 (1999). https://doi.org/10.1023/A:1018956304595
Issue Date:
DOI: https://doi.org/10.1023/A:1018956304595