Polymorphic behavior of phenylephrine hydrochloride and chloroquine diphosphate
Van der Merwe, Elisma
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Objective: Differences in crystal habits resulting in different XRPD-spectra could wrongly be interpreted as different polymorphic forms of the specific drug. The purpose of this study was to determine whether changes in XRPD-diffraction patterns could be the cause of true polymorphs or a change in crystal habits (i.e. crystals with the same internal structure but different external shape). The influence of grinding, milling and sieving on the powders was also investigated. Methods: For phenylephrine hydrochloride two different crystal types were prepared through recrystallisation from different solvents and the physicochemical properties these crystal modifications were determined by means of XRPD and IR. Morphological properties of and differences between the crystal forms were studied using scanning electron microscopy (SEM). Compression (IR-press), grinding (mortar and pestle) and temperature (VT · XRPD) experiments were conducted. For chloroquine phosphate attempts were made to recrystallise the raw material to obtain the high melting polymorphic form. Results: Two different crystal modifications were identified for phenylephrine hydrochloride recrystallised from ethanol and buthanol respectively. These modifications were identified by means of XRPD. The DSCand IR-results were the same but differences could be seen on the SEMphotomicrographs. Temperature studies with the VT XRPD showed that an increase in temperature had no effect on the original XRPD-patterns. After compression and grinding the crystal form recrystallised from buthanol changed to the same crystal form of that recrystallised from ethanol. Single X-ray studies on the two crystal forms were done and showed that both the crystal form from ethanol and butanol had the same crystal structure and were thus of the same polymorph. Efforts to recrystallise chloroquine phosphate failed and the influence of mechanical stress was investigated. After grinding the low melting polimorphic form changed to a mixture of the low and high melting polimorphic forms. Conclusion: The differences in XRPDpatterns of the phenylephrine hydrochloride crystal modifications were found to be due to different crystal habits and differences in particle size because of the habits. The importance of using more than one method of characterisation of raw material was illustrated by this study. Were only the XRPD results used the above differences would have wrongly been attributed to polymorphism. Polymorphism is a complex field of study in which the careful selection of representative techniques directly determines the validity of the identification of different polymorphs or not.
- Health Sciences