Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055.
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055; Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109-1055.
J Pharm Sci. 2018 Oct;107(10):2731-2734. doi: 10.1016/j.xphs.2018.06.020. Epub 2018 Jun 28.
The crystal structure of indinavir sulfate, a pharmaceutical administered as an ethanol solvate, is presented, revealing a unique channel/ionic solvate structure to be characteristic of the compound. The properties of the material with regard to thermal treatment and water adsorption follow closely from the structure. The in situ amorphization of the pharmaceutical upon contacting liquid water is observed and highlights the unique dissolution enhancement of marketing the crystalline solvate dosage. Through survey of published crystal structures, an ambiguous sulfate/bisulfate ionization state is also observed in the crystal, which challenges the general understanding of the pharmaceutical. This study provides a solid-state insight into the function of a special multicomponent crystalline pharmaceutical form.
硫酸茚地那韦,一种以乙醇溶剂合物形式给药的药物,其晶体结构被呈现出来,揭示了该化合物独特的通道/离子溶剂合物结构特征。该物质的热处理和水吸附特性与结构密切相关。在与液态水接触时,药物的原位非晶化被观察到,这突出了市场上销售的结晶溶剂合物剂型的独特溶解增强作用。通过对已发表的晶体结构的调查,也观察到晶体中硫酸盐/硫酸氢盐的电离态不明确,这对药物的普遍认识提出了挑战。本研究为特殊多组分结晶药物形式的功能提供了固态的深入了解。