Indomethacin (IMC) and three types of poly-(vinylpyrrolidone) (PVP 12PF, PVP K30 and PVP K90) were studied in the form of solid dispersion, prepared with the solvent evaporation method, by spectroscopic (Raman, FT-IR, X-ray diffraction), thermal (differential scanning calorimetry, thermogravimetry, hot-stage microscopy), fractal and image analysis. Raman and FT-IR micro-spectroscopy indicated the occurrence of drug/polymer interaction and the presence of an amorphous form of IMC, as also resulting from X-ray diffractometry. Hot-stage microscopy suggested that the interaction between IMC and the polymer occurring on heating of a physical mixture, is common to other acidic compounds and causes a depression of the temperature of the appearance of a molten phase. Co-evaporated particles were coated by spray-congealing process with molten stearic acid for gastroprotection, but also for stabilization of the amorphous structure of the drug: the final particles were spherically shaped. Dissolution tests carried out on the final microparticles showed that the coating with stearic acid prevents IMC release at acidic pH and also protects against recovery of the IMC crystallinity, at least after 9 months of aging: the extent and mode of the release, before and after aging, overlap perfectly. The test revealed a notable improvement of the drug release rate from the solid dispersion at suitable pH, with respect to pure IMC. The comparison of the present solid dispersion with IMC/PVP (surface) solid dispersion obtained by freeze-drying of an aqueous suspension, where IMC maintained its crystalline state, revealed that there was no difference concerning the release rate, but suggested a superior quality of this last process as a mean of improving IMC availability for the easiness of preparation and stability, due to the absence of the amorphous state of the drug, as a possible instability source of the system. Finally, the coating with stearic acid is discussed as a determining process for the practical application of solid dispersions.
Raman and thermal analysis of indomethacin/PVP solid dispersion enteric microparticles.
FINI, ADAMO;CAVALLARI, CRISTINA;OSPITALI, FRANCESCA
2008
Abstract
Indomethacin (IMC) and three types of poly-(vinylpyrrolidone) (PVP 12PF, PVP K30 and PVP K90) were studied in the form of solid dispersion, prepared with the solvent evaporation method, by spectroscopic (Raman, FT-IR, X-ray diffraction), thermal (differential scanning calorimetry, thermogravimetry, hot-stage microscopy), fractal and image analysis. Raman and FT-IR micro-spectroscopy indicated the occurrence of drug/polymer interaction and the presence of an amorphous form of IMC, as also resulting from X-ray diffractometry. Hot-stage microscopy suggested that the interaction between IMC and the polymer occurring on heating of a physical mixture, is common to other acidic compounds and causes a depression of the temperature of the appearance of a molten phase. Co-evaporated particles were coated by spray-congealing process with molten stearic acid for gastroprotection, but also for stabilization of the amorphous structure of the drug: the final particles were spherically shaped. Dissolution tests carried out on the final microparticles showed that the coating with stearic acid prevents IMC release at acidic pH and also protects against recovery of the IMC crystallinity, at least after 9 months of aging: the extent and mode of the release, before and after aging, overlap perfectly. The test revealed a notable improvement of the drug release rate from the solid dispersion at suitable pH, with respect to pure IMC. The comparison of the present solid dispersion with IMC/PVP (surface) solid dispersion obtained by freeze-drying of an aqueous suspension, where IMC maintained its crystalline state, revealed that there was no difference concerning the release rate, but suggested a superior quality of this last process as a mean of improving IMC availability for the easiness of preparation and stability, due to the absence of the amorphous state of the drug, as a possible instability source of the system. Finally, the coating with stearic acid is discussed as a determining process for the practical application of solid dispersions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
