Studies On Preparation And Quality Control Of Polymorphs Of Amifostine

Amifostine is a kind of cytoprotectant, which was first approved by the FDA in 1996, for prevent adverse reaction from chemotherapy. Results of clinical research show that amifostine can selectively protect almost all normal tissue (except for central nervous system), but not for tumor organization. In addition, amifostine will not affect treatment of drugs. Because of amifostine has low drug protective effect, effect time is short, high toxic adverse reactions and no oral activity, so its practical application is limited. Therefore, study on the radioprotector, which has oral activity, high efficiency, low toxicity and long time of effection is the hotspot and developing trend in the future.Preparation of monohydrate amifostine and dihydrate amifostine form trihydrate amifostine, all compounds were characterized by means of IR and 1HNMR. Investigate the anti solvent effect on the yield and moisture content of monohydrate amifostine and dihydrate amifostine, when the anti solvent was methanol, ethanol, acetone, isopropanol, tetrahydrofuran and glycol. When anti solvent was methanol, the yield of monohydrate amifostine and dihydrate amifostine were the highest, and when anti solvent was methanol, the moisture content of monohydrate was least.In this paper, we have studied the stability of monohydrate amifostine, dihydrate amifostine and trihydrate amifostine. In the condition of acceleration test, which temperature was 25℃, during the 6 months the content of monohydrate amifostine was 98.59%-100.64%, the content of dihydrate amifostine was 98.64%-100.56%, the content of trihydrate amifostine was 99.59%-100.64%. The total content of related substances were all less than 0. 30%. Using HPLC, DSC and XRD powder diffraction to compare the stability of polymorphs of amifostine. It turned out that the order of stability was trihydrate amifostine>monohydrate amifostine>dihydrate amifostine.The optimum conditions of preparing micro-nano particle amifostine were obtained by the methods of 4 factors and 4 levels orthogonal test. The 28.2% of amifostine prepared by this condition has the particle size of 2305nm with narrow-dispersed particle size distribution.