Martínez-Ohárriz M C, Martín C, Goñi M M, Rodríguez-Espinosa C, Tros de Ilarduya-Apaolaza M C, Sánchez M
Dpto. Química-Física, Facultad de Ciencias, Universidad de Navarra, Pamplona, Spain.
J Pharm Sci. 1994 Feb;83(2):174-7. doi: 10.1002/jps.2600830212.
Three polymorphs (I, II, and III forms) and a new crystal form (form IV) of diflunisal were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry (DSC), hot-stage microscopy, IR spectroscopy, and dissolution studies. According to the different X-ray diffraction profiles, an identification system for the polymorphs can be developed based on the different peak positions of the diffraction patterns. The mutual transition behavior of the polymorphs was investigated and the melting points and melting enthalpies were determined from DSC and thermomicroscopy data. All forms first recrystallize to the more stable form (form I) and then melt at 210 degrees C; only one weak transition peak was detected corresponding to transformation of form III to form I. Differences observed in IR spectra indicate that intramolecular hydrogen bonding occurs between hydroxyl and carbonyl groups and/or between fluorine atoms. The intrinsic dissolution rates were determined from compressed disks in an aqueous medium. Unexpectedly the dissolution rate of form IV was lower than that of the most stable modification form I.
制备了二氟尼柳的三种多晶型物（I型、II型和III型）以及一种新晶型（IV型），并通过粉末X射线衍射、差示扫描量热法（DSC）、热台显微镜、红外光谱和溶出度研究对其进行了表征。根据不同的X射线衍射图谱，基于衍射图案的不同峰位置可开发出一种多晶型物鉴定系统。研究了多晶型物的相互转变行为，并根据DSC和热显微镜数据确定了熔点和熔化焓。所有晶型首先重结晶为更稳定的晶型（I型），然后在210℃熔化；仅检测到一个对应于III型向I型转变的弱转变峰。红外光谱中观察到的差异表明，羟基与羰基之间和/或氟原子之间发生了分子内氢键作用。通过在水性介质中压制片测定了固有溶出速率。出乎意料的是，IV型的溶出速率低于最稳定的I型变体。
