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硝硫氰胺难溶于水,其吸收受溶解速度所限制。微粉化减低粒子大小后,通常可增加吸收和总生物利用度。但由微粉化而得到粒子的巨大表面上所附有的自由能,使其成为热力学不稳定体系。选择无生理活性、易溶载体聚乙二醇6000,以熔融法制备成固体分散物。X-射线衍射实验证实为热力学稳定的间充固体溶液。发现硝硫氰胺-聚乙二醇6000(1:9)固体分散物的溶解速度,分别为微粉化和纯硝硫氰胺的10.6倍和15倍。小白鼠体内研究,微粉化硝硫氰胺24小时血浓曲线下的总面积,只有硝硫氰胺-聚乙二醇6000固体分散物的59%。
Nitrosamines are poorly soluble in water and their absorption is limited by the rate of dissolution. Micronization reduces particle size and generally increases absorption and overall bioavailability. However, the free energy attached to the macroscopic surface of the particles resulting from micronization renders them thermodynamically unstable. Choose non-physiologically active, soluble carrier polyethylene glycol 6000, prepared by melt method into a solid dispersion. X-ray diffraction experiments proved to be thermodynamically stable filled solid solutions. It was found that the dissolution rate of the solid solution of the nitrocyanamine-polyethylene glycol 6000 (1: 9) was 10.6-fold and 15-fold, respectively, of the micronized and pure nitrosamines. In vivo studies in mice, the total area under micronized nitrosamines 24 hour blood concentration curve, only 59% of the nitrites - polyethylene glycol 6000 solid dispersion.