Risperidone chloride 2.5-hydrate: a new crystalline form

Abstract

Key indicatorsSingle-crystal X-ray study T = 298 K Mean (C-C) = 0.002 Å Disorder in solvent or counterion R factor = 0.041 wR factor = 0.101 Data-to-parameter ratio = 18.1For details of how these key indicators were automatically derived from the article, see

Crystalline form B of risperidone

“…The molecule contains a piperdine ring, with one end connected to a pyridopyrimidine group via an ethylene bridge, while the other end is connected to an almost planar fluorobenzisoxazole ring system. The molecular conformation of (I) is in agreement with that of the previously reported risperidones (Peeters et al, 1993;Wang & Pan, 2006;Ravikumar et al, 2005).…”

“…It has useful central nervous system activity and shows a wide range of therapeutic effects. Up to now, six crystalline forms of risperidone have been reported (Krochmal et al, 2004;Reddy et al, 2004;Strelice & Nijmegen, 2004) and characterized by X-ray powder diffraction patterns, but only two of their crystal structures (Form A and risperidone hydrochloride hemipentahydrate) have been determined (Peeters et al, 1993;Wang & Pan, 2006). We report here the crystal structure of form B.…”

Physicochemical characterization of neuroleptics. Relative stability of 7- and 9-hydroxyrisperidones and their protonated forms in gas phase and in solution

“…In 7-OH-RSP the most favourable orientation of the OH group relative to the molecular framework is the same as in the model compound with f C6ÀC7-O-H ¼ À66.9 in gas and À68.3 in water. Computed geometrical parameters are in good agreement with the corresponding experimental data for both neutral [20,21] and N 15 -protonated forms [23] of the parent compound. In vacuum 9-OH-RSP exists as intramolecularly hydrogen bonded structure, as expected from previous results on the model compound.…”

“…In facts, according to Zughul et al [22] pKa 1 and pKa 2 of RSP are 3.1 and 8.1, respectively. So at the physiological pH ¼ 7.4 RSP is prevailingly present as a monoprotonated form, protonation occurring at the piperidine N 15 atom [23]. The ratio between ionized and neutral form can be calculated by ½OH À RSP À H þ =½OH À RSP ¼ 10 pKa2À7:4 which gives 83% of the ionized form.…”

Polymorphism and Solvatomorphism 2006

“…118 The chloride salt of risperidone was shown to crystallize in a 2.5-hydrate structure, where hydrogen bonding was found to link the water molecules and chloride anions to the risperidone cations. 119 It was shown that the hemi-pentahydrate form of risedronate can lose one equivalent of channeltype water when heated at 608C, or when exposed to low relative humidity (less than 10% RH). 120 Removal of the channel water was then found to induce a structural change that produced a new crystal phase.…”