Mirza Sabiruddin, Miroshnyk Inna, Heinämäki Jyrki, Christiansen Leena, Karjalainen Milja, Yliruusi Jouko
Pharmaceutical Technology Division, Department of Pharmacy, University of Helsinki, Finland.
AAPS PharmSci. 2003;5(2):E12. doi: 10.1208/ps050212.
The influence of the organic solvents widely used in the pharmaceutical industry (acetone, methylethylketone, ethanol, and isopropanol) both in the presence and in the absence of water on the crystallization behavior of erythromycin (Em), a clinically relevant antibiotic of the macrolide group, was investigated. It was observed that despite a high preference for water as a guest molecule, Em rather easily forms solvates with the organic solvents studied. Consequently, 4 distinct solvates of Em have been isolated by recrystallization: acetonate, methylethylketonate, ethanolate, and isopropanolate. It was established that in a pure organic solvent, or 1:9 or 1:1 water-organic solvent mixtures, the corresponding solvate is always crystallized. However, the recrystallization of erythromycin from 2:1 water-organic solvent (excluding methylethylketone) mixture results in the formation of a crystal hydrate form. X-ray powder diffraction revealed the isostructurality of the solvates with acetone and methylethylketone. Thermogravimetric analysis showed that the loss of volatiles by all of the solvated crystals is nonstoichiometric. The desolvation behavior of the solvates with the organic solvents studied by means of variable-temperature x-ray powder diffraction indicates that in contrast to erythromycin dihydrate, they belong to a different class of solvates--those that produce an amorphous material upon desolvation.
研究了制药工业中广泛使用的有机溶剂（丙酮、甲乙酮、乙醇和异丙醇）在有水和无水情况下对红霉素（Em）结晶行为的影响。红霉素是一种临床上常用的大环内酯类抗生素。结果发现，尽管Em对水分子有较高的亲和性，但它仍能很容易地与所研究的有机溶剂形成溶剂化物。因此，通过重结晶分离出了4种不同的Em溶剂化物：丙酮化物、甲乙酮化物、乙醇化物和异丙醇化物。研究确定，在纯有机溶剂中，或在水与有机溶剂比例为1:9或1:1的混合溶剂中，总是会结晶出相应的溶剂化物。然而，从水与有机溶剂比例为2:1的混合溶剂（不包括甲乙酮）中重结晶红霉素会生成结晶水合物形式。X射线粉末衍射显示丙酮化物和甲乙酮化物的溶剂化物具有同构性。热重分析表明，所有溶剂化晶体的挥发物损失都是非化学计量的。通过可变温度X射线粉末衍射研究的有机溶剂溶剂化物的去溶剂化行为表明，与红霉素二水合物不同，它们属于另一类溶剂化物——去溶剂化时会产生无定形物质的溶剂化物。
