{'fraction_non_alphanumeric': 0.03451463790446841, 'fraction_numerical': 0.017257318952234205, 'mean_word_length': 5.427722772277228, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Aspirin polymorphism questioned

Aspirin, crystallized under various conditions, has recently been reported to display different melting points (Tawashi, 1968; Summers, Carless & Enever, 1970), heats of fusion (Tawashi, 1969), densities (Summers & others, 1970), and rates of dissolution (Mitchell & Saville, 1967, 1969; Tawashi, 1968). These differences were ascribed in every case to polymorphic behaviour. It seems, however, that this conclusion is not warranted by the submitted evidence, and that other explanations for the observed differences should be considered. Particularly disturbing is the failure of the supposedly discrete structures, i.e., “polymorphs,” to exhibit different x-ray powder diffraction properties. Even the one possible exception-described only as diffraction “differences” by Tawashi (1968)may well have been due to preferred crystal orientation, inasmuch as two forms of extremely different shape, i.e., prisms and needles, were compared. Mitchell & Saville (1 968) proposed that x-ray diffraction methods failed to distinguish between two forms of aspirin because the forms were mixtures of polymorphs. In view of the fact that the powder diffraction data from commercial aspirin (presumably Form B) is reconcilable with the single crystal data (Smith, 1962), however, their proposal is questionable. The findings of Summers & others (1970) that there are six polymorphs of aspirin and that these range in density from 1.29 to 1.50 g/ml but have similar difjaction properties are not consistent with the usual concepts of crystal structure and polymorphism. It is unfortunate that the cited authors did not describe their crystals with regard to size and habit ; variables that may conceivably have affected the various measurements. For example, differenczs in size and habit might: (a) Affect the dissolution rate from a pressed disc through differences in capillarity or wetting ; (b) affect the determination of melting point and heat of fusion through differences in rates of sublimation and decomposition. Aspirin has a long history of giving trouble in melting point determinations (Hayman, Wagener & Holden, 1925) ; (c) affect density measurements by variously interfering with the complete filling of cavities by the displacement fluid. Another proposal consistent with the published observations would be that the crystals somehow differ with regard to imperfections, stresses or finer structural details, but these differences also would not justify the use of polymorphic designations. Whatever the source of the apparent extra thermodynamic activity exhibited by some of the aspirin crystals, exposure to heat, ultrasound, solvent, etc. could cause them to anneal, grow or ripen ; they would thus mimic polymorphic behaviour by reverting to a “more stable” form but would not undergo changes in their routinely determined x-ray diffraction properties. In the interest of preserving the meaning of the term “polymorphism,” it would be helpful if future publications on the subject of aspirin polymorphism were to clarify the questions raised in this letter. Furthermore, all articles claiming the existence of polymorphs should include explicit directions for their preparation and identification. 75