Crystallographic Structure, Intermolecular Packing Energetics, Crystal Morphology and Surface Chemistry of Salmeterol Xinafoate (Form I)

Alexandru A. Moldovan, Ian Rosbottom, Vasuki Ramachandran, Christopher M. Pask, Oboroghene Olomukhoro, Kevin J. Roberts
2017 Journal of Pharmaceutical Sciences  
Single crystals of salmeterol xinafoate (form I), prepared from slow cooled supersaturated propan-2-ol solutions, crystallise in a triclinic P1 symmetry with two closely related independent salt pairs within the asymmetric unit, with an approximately double unit cell volume compared to the previously published crystal structure 1 . Synthonic analysis of the bulk intermolecular packing confirms the similarity in packing energetics between the two salt pairs. The strongest synthons, as expected,
more » ... are dominated by coulombic interactions. Morphological prediction reveals a plate-like morphology, dominated by the {001}, {010} and {100} surfaces, consistent with experimentally grown crystals. Though surface chemistry of the slow growing {001} face comprises of large sterically hindering phenyl groups, weaker coulombic interactions still prevail from the alcohol group present on the phenyl and hydroxymethyl groups. The surface chemistry of the faster growing {010} and {100} faces are dominated by the significantly stronger cation/anion interactions occurring between the carboxylate and protonated secondary ammonium ion groups. The importance of understanding the cohesive/adhesive nature of the crystal surfaces of an API, with respect to their interaction with other API crystals and excipients and how that may impact formulation design is highlighted. List of Symbols E cr = Lattice energy E att = Attachment energy E sl = Slice energy = Surface specific anisotropy factor kcal = kilocalories List of Terms DSC = Differential scanning calorimetry SX = Salmeterol xinafoate XRD = X-ray diffraction vdW = van der Waals H-bonds = Hydrogen bonds API = Active Pharmaceutical Ingredient This paper reports the crystal structure of the form I of Salmeterol Xinafoate, as obtained using single crystal XRD data. Based on this, the intermolecular packing energetics, morphology and the surface chemistry of the morphologically important surfaces were characterised. Materials and Methods Materials A supply of micronised SX was acquired from Vamsi Labs Ltd. (Chincholi, Solapur, Maharashtra, India) with batch number SX-0030513.
doi:10.1016/j.xphs.2016.11.016 pmid:27894968 fatcat:jdodts2ucrg23p3kbmeurmjepe