The polymorphism of aspirin

Mitchell & Saville (1967) demonstrated that various samples of commercial aspirin have different rates of dissolution. Subsequently, Tawashi (1968, 1969) has reported the existence of aspirin in two polymorphic forms (designated Forms I and 11). During the course of present work concerned with the tabletting characteristics of various polymorphic forms of drugs, we have been able to identify several aspirin polymorphs in addition to those already reported. Table 1 shows the conditions under which the polymorphs were obtained. Confirmatory evidence that all the samples examined were aspirin and differed only in crystalline form is afforded by the fact that no differences could be detected in their ultraviolet spectra when dissolved in ethanol (determined using a Unicam SP800 recording spectrophotometer). A Perkin-Elmer Differential Scanning Calorimeter DSC-1 equipped with an effluent analyser was used for the thermal analysis of the polymorphs. Samples weighing between 2 and 10 mg were analysed using a scanning rate of 8" min-l. No traces of solvent of crystallization were detected by the effluent analyser when any of the aspirin samples were fused. This therefore excludes the possibility that the samples were solvated forms of aspirin. The DSC traces for the six polymorphs are shown in Fig. 1. A Kofler hot stage microscope was used to confirm the melting points of the polymorphs. The results are shown in Table 1. The instrument was also used to observe solution phase transformations of pairs of polymorphs. The solvent for this work was n-pentanol saturated with one component of the particular polymorph pair under study. Some of the phase transformations are summarized in Table 2. Since different polymorphs have different crystal packing conditions, it is to be expected that they will have different true densities. Density determinations were made at 20" using a specific gravity bottle with a displacement medium of light liquid paraffin. Table 1 contains the results of this work.