The Dimorphism of Sulfathiazole

Abstract

DWOWHXSM OF SIJLFATEIAZOLE 97plotted from the data should present unique characteristics. This is not obvious in the figure though the curves have attained a linear form from about this temperature to the lowest temperature investigated which was -50'. Clearly we may not describe the water which freezes only a t temperatures below -22' in terms of ordinary phase equilibria. That which freezes at temperatures between zero and -2 2 O might be so described if it is considered as compressed but other evidence indicates that orientation of the dipoles would complicate the interpretation. In conclusion it may be stated that the present data are in general agreement with the previous studies".' and while compression occurs a t the solid-liquid interface, the properties of the liquid are additionally modified in this region.summary By means of the calorimetric method, determinations have been made of the unfrozen water on the surface of wetted silica gel and carbon a t temperatures from 0 to -50'.Basing a comparison on unit quantities of the solids, the silica binds the water more strongly than the carbon.The entrance of the new drug, sulfathiazole (2-sulfanilamidothiazole),' into the field of chemotherapy made a survey of its physical and chemical properties essential. In the course of this study, it was found that sulfathiazole occurred in two distinct crystalline forms. The conditions for the existence and isolation of these dimorphs and their physical properties are herein presented.Hexagonal Form.-When sulfathiazole was crystallized from water, acetone. or ethyl or methyl alcohol, hexagonal prisms ( Fig. 1) were formed. They were obtained easily by preparing a saturated solution of the material in ethyl alcohol on the steam-bath, removing the container from the bath and allowing to cool slowly to room temperature. The crystals were then filtered off and dried in the air. On heating the hexagonal prisms on the Fisher the other hand, if the temperature was raised slowly, most of the crystals would have become opaque before reaching 173'. micromelting point stage and observing under the microscope, part of them remained clear and melted at approximately 173 to lis0, while others suddenly turned white or opaque throughout and did not melt until the temperature reached 2W202". This indicated that some of the crystals had undergone a transition to the higher melting form, and the extent of this transition has been found to depend to a large extent upon the rate of heating. Thus, if the stage was preheated to about 175', it was possible to observe all the crystals melting a t this temperature. On (11 P-binder and Wdtcrri. 'In19 JOUINAL, 61, 2032 11839).Fig. 1.-Hexagonal prisms ( X SO)Rod Form.-An attempt was made to isolate a second type of crystal by fractional crystallization from hot ethyl alcohol; however, all fractions obtained in this manner were of the hexagonal form. Consideration was then given to the fact that when the hexagonal form became opaque upon heating on the melting point stage, it had in reality undergo...

Rate of Crystal Growth of Sulfathiazole and Methylprednisolone

“…In addition, refractive index determinations were used to characterize the long axes of the individual crystals of both compounds. The refractive index of the long axis of the hexagonally shaped face of sulfathiazole crystal was found to be 1.674, in agreement with the reported value (8). For methylprednisolone the refractive index along the long axis of the rod-shaped crystal was found to be 1.602 (9).…”

Application of differential scanning calorimetry to the study of sulphathiazole crystal forms

“…175'1. This form therefore appears to be another variety of Form I since it has the same infrared spectrum and heat of transition and it is not justifiable to call it a new form. Grove & Keenan (1941) Milosovich (1964 and Brandstaetter-Kuhnert & Martinek (1965) all quoted a melting point of 175" for Form I which could be due to heating the sample at a rapid rate when melting occurs at 175" without polymorphic transition, as noted by Guillory (1967). Variation of the transition temperature of I and I1 could be interpreted on the basis of the factors discussed earlier.…”

Sulfathiazole polymorphism studied by magic-angle spinning NMR

“…[1][2][3][4][5][6][7] It has been described as the classic polymorphic system. 3 We have recently demonstrated that there are at least five polymorphs of sulfathiazole, and we have carried out a singlecrystal structure determination of the fifth polymorph, 7,8 although it now appears that this polymorph was the one first synthesized, 9 first described in a patent, 10 and first published in the literature by two independent groups, 11,12 but subsequently overlooked for more than 40 years.…”

“…13 It would seem that all five polymorphs had been seen and described by 1947, but not clearly differentiated. 1,2,11,12,14 Furthermore, we have shown that the common material of commerce does not have the polymorphic structure described by Kruger and Gafner,15 as has been assumed for a quarter of a century, but has the structure first determined by Babilev et al 16 The sources of confusion which have led to this unusual situation are 5-fold, namely the irreproducibility of the crystallization, the tendency to crystallize as mixtures, the close similarity in structure and properties of three of the polymorphs, the sample-to-sample variability in stability, and the differences between the pharmaceutical and crystallographic enumeration of the polymorphs. In order for the present discussion to be clear, Table 1 sets out the nomenclature of the polymorphs.…”