Investigations on the thermal behavior of omeprazole and other sulfoxides.
Thermoanalytical and chromatographic investigations were performed to elucidate the reason for the uncommon thermal behavior of omeprazole prepared according to a newly developed route of synthesis. Differential scanning calorimetry revealed that the position of the melting endotherm of omeprazole strongly depended on the heating rate. High heating rates (20-30 degrees C/min) led to endothermic peaks at high temperatures (comparable to literature data), while lower rates induced a shift of the signal to lower temperatures. In thermogravimetric experiments weight loss was observed which started about 20 degrees C lower at the heating rate of 1 degrees C/min in comparison with the rate of 20 degrees C/min. Thermomicroscopic investigations indicated a decomposition prior to melting at low (1 degrees C/min) but not at high heating rates (20 degrees C/min). Investigation of the violet melt by HPLC and TLC showed that omeprazole was decomposed quantitatively. Decomposition started at 135 degrees C and depended on the rate of heating. The results indicate that eutectic behavior with decomposition products leads to a melting point depression of omeprazole upon slow heating. Similar behavior was observed for the related sulfoxides lansoprazole and pantoprazole which showed the same onset temperature for decomposition as omeprazole in chromatographic investigations. The heating rate dependent melting behavior was, however, much less pronounced for pantoprazole which has a melting range only slightly above the onset temperature for decomposition. In contrast, a constant value for the melting temperature could not be achieved for lansoprazole, the substance with the highest melting range under investigation, even at high heating rates up to 30 degrees C/min. In conclusion, a very dynamic method and exactly standardized measurement conditions, particularly with regards to heating rate, (e.g., in DSC) have to be employed to enable reliable determination of a melting point of these decomposable substances.
Rosenblatt
K M
KM
Institute of Pharmacy, Friedrich-Schiller-Universität, Jena, Germany.
Bunjes
H
H
Seeling
A
A
Oelschläger
H
H
D000897:Anti-Ulcer Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004055:Differential Thermal Analysis; D004355:Drug Stability; D009853:Omeprazole / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013454:Sulfoxides / Q000737:chemistry*; D013818:Thermogravimetry
D000897:Anti-Ulcer Agents; D011720:Pyrazoles; D013454:Sulfoxides; D009853:Omeprazole