Felodipine–diazabicyclo[2.2.2]- octane–water (1/1/1) Katarzyna A. Solanko, a Artem O. Surov, b German L. Perlovich, b Annette Bauer-Brandl a and Andrew D. Bond a * a Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark, and b G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Academicheskaya St. 1, 153045 Ivanovo, Russia Correspondence e-mail: adb@chem.sdu.dk Received 5 October 2012 Accepted 18 October 2012 Online 31 October 2012 The title compound, C 18 H 19 Cl 2 NO 4 C 6 H 12 N 2 H 2 O, is a co- crystal hydrate containing the active pharmaceutical ingre- dient felodipine and diazabicyclo[2.2.2]octane (DABCO). The DABCO and water molecules are linked through O—HN hydrogen bonds into chains around 2 1 screw axes, while the felodipine molecules form N—HO hydrogen bonds to the water molecules. The felodipine molecules adopt centrosym- metric back-to-back arrangements that are similar to those present in all of its four reported polymorphs. The dichloro- phenyl rings also form -stacking interactions. The inclusion of water molecules in the cocrystal, rather than formation of N—HN hydrogen bonds between felodipine and DABCO, may be associated with steric hindrance that would arise between DABCO and the methyl groups of felodipine if they were directly involved in hydrogen bonding. Comment Felodipine [systematic name: ethyl methyl 4-(2,3-dichloro- phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate] is a calcium-channel blocking agent that is widely used for the treatment of hypertension and angina (Nussinovitch et al., 1996). The compound belongs to Class II of the Biopharma- ceutical Classification Scheme (Amidon et al., 1995) because it is effectively absorbed from the gastro intestine but is prac- tically insoluble in water. One strategy that might be applied to enhance the aqueous solubility of felodipine is to generate alternative solid forms (Hilfiker et al., 2006). To this end, we have recently reported the structures and properties of four felodipine polymorphs (Surov et al., 2012). We have also carried out some cocrystallization trials and we report here the structure of a hydrated cocrystal, (I), of felodipine with diazabicyclo[2.2.2]octane (DABCO). The asymmetric unit of (I) comprises one molecule of felodipine, one molecule of DABCO and one water molecule (Fig. 1). The conformation of the felodipine molecule is typical for this class of molecule (Goldmann & Stoltefuss, 1991), comprising two approximately planar sections with the dichlorophenyl unit lying perpendicular to the plane of the remainder of the molecule. The 1,4-dihydropyridine (1,4- DHP) ring (N1/C1–C5) adopts a shallow boat conformation, in which atoms N1 and C3 lie 0.135 (4) and 0.293 (4) A ˚ , respectively, from the mean plane defined by atoms C1/C2/C4/ C5. These values are consistent with a previous database study for 1,4-DHP rings (S¸ ims¸ek et al., 2000), which showed that atom C3 typically lies 0.30 A ˚ from the defined plane, while the deviation of atom N1 lies in the range 0.04–0.19 A ˚ . The dihedral angle between the dichlorophenyl ring and the mean plane defined by atoms C1/C2/C4/C5 is 90.00 (8)  . The O atoms of the methyl and ethyl ester groups are approximately in the plane of the 1,4-DHP ring on account of -electron conjuga- tion between the oxo groups and the double bonds in the ring. The DABCO and water molecules are linked through O— HN hydrogen bonds (Table 1) into chains around the 2 1 organic compounds o456 # 2012 International Union of Crystallography doi:10.1107/S0108270112043405 Acta Cryst. (2012). C68, o456–o458 Acta Crystallographica Section C Crystal Structure Communications ISSN 0108-2701 Figure 1 The molecular structure of (I), with displacement ellipsoids drawn at the 50% probability level for non-H atoms.