Inclusion of the Antidepressant Paroxetine in β-cyclodextrin

The X-ray structure and thermal stability of a β-cyclodextrin inclusion complex of the antidepressant paroxetine [(3S-trans)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine], with the formula ( β-cyclodextrin)2...paroxetine...28H2O, are reported. On heating, the crystals dehydrate in two stages and begin to decompose from approximately 270 °C. An X-ray diffraction study at 173K showed that the complex crystallizes in the monoclinic system, space group P21 with a = 15.2262(3), b = 31.4771(1), c = 15.6739(1) Å, β = 104.320(1)° and Z = 2 formula units. Refinement on F2 converged at R1 = 0.066, wR2 = 0.182 (21478 reflections). On encapsulation within a head-to-head β-cyclodextrin dimer, the paroxetine molecule adopts an unusual `hairpin' conformation, stabilised by intramolecular π...π interaction between the phenyl rings. The guest piperidine ring is located at the primary face of one host molecule of the dimer while the fluorophenyl and benzodioxole moieties respectively occupy the dimer interfacial region and the cavity of the second host molecule. Experimental and computed X-ray powder diffraction patterns for the complex are also reported. The mode of stacking of the dimeric complex units is shown to be one of at least three distinct variants which can be identified for β-cyclodextrin complexes with similar unit cell dimensions and crystallizing in the same space group.