Stable hydrate of a muscarinic receptor antagonist
View Patent ↗A stable solid hydrate of a muscarinic receptor antagonist is useful in the treatment of irritable bowel syndrome, diverticular disease, oesophageal achalasia, chronic obstructive airways disease, over active bladder (including symptoms of incontinence, urge and frequency), urinary incontinence, neurogenic urinary urgency or pollakiuria, treatment of bladder functional disorder, urinary leakage, painful or difficult urination caused by neurogenic bladder, spastic or hypertonic bladder, dysfunctional bladder syndrome, gastrointestinal disorders including gastrointestinal hyperactivity, and relaxing effect on intestinal smooth muscle cells.
1. A solvate of darifenacin of the formula (VIII):
2. A solvate according to claim 1 characterised by an infra-red spectrum, run using single reflection ATR (attenuated total reflectance), which shows significant absorption bands at ν max. (cm −1 ): 3463, 3342, 3299, 3285, 3022, 2925, 2825, 1673, 1614, 1490, 1440, 1384, 1333, 1319, 1243, 1195, 1152, 1130, 1115, 1102, 1028, 1003, 980, 939, 926, 907.
3. A solvate according to claim 1 which is characterised by a powder X-ray diffraction pattern obtained using copper radiation (λ=0.15405 nm) which shows main peaks at 12.572, 12.754, 15.978, 17.419, 18.537, 18.889, 20.78, 21.562, 22.437, 22.736, 23.767, 24.075, 24.266, 25.35, 25.762, 27.214, and 29.716 degrees 2θ.
4. A solvate according to any of claims 1 which is characterised by a scanning calorimetry (DSC) trace which shows a sharp endotherm at 92° C. at a scan rate of 20° C./min.
5. A process for providing a solvate of formula (VIII) according to claim 1 , comprising subjecting (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide to an ion-exchange resin treatment followed by mixing with toluene.