PROCESS FOR THE PRODUCTION OF POLYMORPH OF CIMETIDINE

• Main Authors: BAVIN, PATRICK M.G, TOVEY, GEOFFREY D, SLY, JAMES C.P, WARD, RICHARD J
• Format: Patent
• Language: English; French
• Published: 24.02.1981
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

A process is provided for the production of a substantially crystallographically pure polymorphic form of cimetidine having the structural formula Such cimetidine is characterized by an infra red spectrum (1% KBr disc) having very strong, broad peaks at 1400 and 1385 cm-1, a strong, sharp peak at 1205 cm-1 and a medium-sharp peak at 1155 cm01 and having no peak at 1180 cm-1. The process includes dissolving cimetidine in a hot, nonaqueous solvent, e.g., acetonitrile, acetone, methylisobutylketone, toluene or a lower alkanol. The resultant solution is cooled with sufficient agitation to ensure efficient heat transfer to yield a suspension of cimetidine A in the solvent. The suspension is now characterized by good handling properties. Finally, the cimetidine A is separated off. Suchcimetidine A is more easily obtainable in a crystallographically pure state. It is also slightly more water soluble than either of the other forms, and preferably has a rate of dissolution at 25.degree.C. from the flat sur-face of a standard compressed disc of at least 0.20 mg/min/cm2. A further advantage is that such cimetidine A is rather more easy to handle, particularly in large scale operations, such as centrifugation.