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Fluticasone propionate is a new type of glucocorticoid drugs, clinical application of the treatment of asthma, allergic rhinitis, chronic infarct pneumonia, such as atopic dermatitis. The drug has strong efficacy and less adverse reactions, and it is free in the domestic market. So it is valuable to research.The main task was to find a mature, stable and suitable technology line for industrial production and to study the quality of the products after pilot amplification. It included four parts:new method for synthesis of laboratory research, pilot amplification, waste disposal and the quality of research.Fluoride Betamethasone was prepared from Dexamethasone Acetate by acetylation, fluoride, hydrolysis of a three-step reaction. and the target product was prepared by oxidation, sulfhydryl, esterification, and fluorine methylation. After single-factor optimization experiments, the total yield of six-step reaction was 52.84%; The product was identificated by Rf value of TLC and retention time of HPLC. The chemical structure of Fluticasone Propionate was confirmed by infrared absorption spectroscopy, MS and NMR. It is originative to the one-pot reaction and the post-processing in the acylation.Betamethasone fluoride was purificated through column chromatography for two times and the yield was relatively low, nearly 61.6%. So the technology was not mature enough to enlarge the production. However, the small test process that fluticasone propionate prepared from fluoride betamethasone was stable and feasible. Response to the above, we carried out pilot studies through the accumulation of process data, quality control of intermediates, process optimization of the pilot. And we solved the problems after the amplification.The total yield of amplification was 85.19%. It was demonstrated that the amplification process was stable and feasible by repeatability test.Finally, we studied the quality of Fluticasone Propionate systematicly. The characters and physical constants were studied by appearance, solubility, absorption coefficient, melting point, solubility and rotatio according to Chinese Pharmacopoeia 2005 EditionⅡ. The related substance, the content, and the stability was detected by HPLC according European Pharmacopoeia.The performance of analytical methods and experimental validation of indicators, including the linear and the scope of the recovery, precision and stability. The results showed that the method was feasible. The purify of three batches of samples was greater than 98%.
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