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 hydrate having the formula (IX)
which is characterized by a powder X-ray diffraction pattern obtained using copper radiation (λ=0.15405 nm) which shows main peaks at 8.39, 10.519, 13.272, 13.693, 15.908, 16.289, 16.855, 19.637, 21.135, 21.55, 21.722, 23.006, and 26.284 degrees 2.theta.
2. A hydrate 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 ): 3625, 3516, 3440, 2948, 2806, 1699, 1622, 1597, 1578, 1488, 1471, 1445, 1378, 1353, 1325, 1312, 1280, 1242, 1196, 1152, 1119, 1102, 1086, 1024, 981, 939, 925, 900.
3. A hydrate according to claim 1 which is characterised by a differential scanning calorimetry (DSC) trace showing a sharp endotherm at 101° C. at a scan rate of 20° C./min.
4. A process for providing hydrate, as defined in claim 1 , in pharmaceutically pure form comprising subjecting (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide to an ionic exchange resin treatment followed by conversion to a toluene solvate which is in turn converted to said hydrate.
5. A process according to claim 4 further including the step of converting the hydrate to an acid addition salt of (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide.
6. A process according to claim 5 , wherein said acid addition salt is the hydrobromide salt.