Sumatriptan succinate. Improved method
Publication Date: 2005-May-04
The IP.com Prior Art Database
An improved method of preparation of Sumatriptan succinate, which gives a well balanced salt.
AN IMPROVED METHOD TO OBTAIN SUMATRIPTAN SUCCINATE
Sumatriptan, having the following formula and its pharmaceutically related salts are therapeutically used as anti migraine agents.
Sumatriptan and related compounds may be prepared by the procedures disclosed in US 4816470 and US 5037845. When a salt of Sumatriptan is formed with a dicarboxilic acid, such as succinic acid, the salt may be formed with either one or both of the carboxylic acid groups, i.e. the salt may contain either one or two moles of Sumatriptan per mole of acid. A preferred salt, disclosed in the literature, is the 1:1 succinate.
Nevertheless, when we performed the process of succinate salt formation described in the literature (example 19, US 5037845) we realised that the method was not robust when scaling-up. Sumatriptan succinate obtained following this method at scaling-up tests did not meet the Assay requirements since the proportions of Sumatriptan and succinic acid were not well balanced in the final product.
There is a need to produce Sumatriptan succinate in a pure and crystalline form according with pharmaceutical requirements and specifications.
Furthermore, the process needs to be consistent with large-scale production.
We have studied different solvents in order to obtain Sumatriptan succinate in a reproducible and consistent process.
An example of this process can be summarize as follows:
- dissolve a mixture of Sumatriptan base and succinic acid in a mixture of an organic solvent and water at elevated temperature,
- clarify the solution,
- add at elevated temperature an organic solvent to precipitate the product,
- allow crystallisation of the product,
- cool down the resultant suspension to 0-5ºC and
- isolate the product by centrifugation.
The following table illustrates the trials perfor...