The structures of two neutral and 17 salt forms of the base (1R, 2S)-(-)-ephedrine are reported. These structures are discussed in the light of the conformers of the ephedrine moiety, the existence of bilayers and the structure determining role of the counterions. Overall, most of the salt structures are essentially derived from the observed packing of the neutral base and are dominated by the amphiphilic nature of the ephedrine molecular structure. In a few cases the size and hydrophobicity of the counterion disrupts this behaviour.
Salt selection is critical in the drug development process as selection of an appropriate form can reduce significantly the time to market of a new pharmaceutical entity. Salt formation is often employed to modify the final drug product. It is a simple chemical modification that can change to advantage the physiochemical, formulation, biopharmaceutical and therapeutic properties of a drug without varying the basic chemical structure. Crystal engineering is the understanding of intermolecular interactions in the context of crystal packing and in the utilisation of such understanding in the design of new solids with desirable physical and chemical properties. 1 The aim being to establish reliable connections between molecular and supramolecular structure on the basis of intermolecular interactions. 2 Taking the known synthesis and structure of the hydrochloride salt as a starting point, novel salt forms of the pharmaceutical base ephedrine have been crystallised and the crystal structures subsequently solved. 3 The hydrogen bonding networks have been described and the relationship between structure and crystal morphology evaluated.
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