Lactam-free amino acids
AssigneeGodecke Aktiengesellschaft
InventorsHelmut Augart, Uwe Gebhardt, Wolfgang Herrmann
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Abstract
The present invention concerns cyclic amino acids of formula ##STR1## substantially free from the lactam ##STR2## wherein n is an integer of from 4 to 6, a process for the preparation thereof, compositions containing the compounds and methods of using them.
Claims11
A process for the preparation of a compound of Formula VII ##STR17## wherein n is an integer of from 5 containing less than 0.5% by weight of a compound of Formula VIII ##STR18## wherein n is as defined above and less than 20 ppm of an anion of a mineral acid comprising:
- (a) hydrolysis of a compound of Formula VII containing a compound of Formula VIII or of a compound of Formula VIII alone with a mixture of equal volumes of a concentrated mineral acid and water to afford an acid addition salt of a compound of Formula VII and
- (b) converting the acid addition salt of a compound of Formula VII by ion exchange to a compound of Formula VII containing less than 0.5% by weight of a compound of Formula VIII and less than 20 ppm of an anion of a mineral acid.
A process for preparing stable and pure pharmaceutical compositions containing a compound of formula (VII) ##STR19## wherein n is an integer of 5 and pharmaceutically acceptable adjuvants consisting of the steps of
- (a) hydrolysis of a compound of formula VII ##STR20## wherein n is as defined above containing a compound of formula VIII ##STR21## wherein n is as defined above or a compound of Formula VIII alone with a mixture of equal volumes of a concentrated mineral acid and water to afford an acid addition salt of a compound of formula VII substantially free of a compound of formula VIII,
- (b) converting the acid addition salt of a compound of formula VII by ion exchange to a compound of formula VII containing less than 0.5% by weight of a compound of formula VIII, wherein the proportion of remaining anion of a mineral acid does not exceed 20 ppm,
- (c) adding pharmaceutically acceptable adjuvants to form a pharmaceutical composition wherein the adjuvants do not promote the formation of a lactam of formula VIII ensuring that the lactam formation under the storage conditions at 25.degree. C. and an atmospheric humidity of 50% does not increase within a period of time of one year after the production of the pharmaceutical compositions or of the active material by more than 0.2% by weight, referred to the pure active material.
A stable and pure pharmaceutical composition in unit dry medicinal dosage form consisting essentially of:
- (i) an active ingredient which is gabapentin in the free amino acid, crystalline anhydrous form containing less than 0.5% by weight of its corresponding lactam and less than 20 ppm of an anion of a mineral acid and
- (ii) one or more pharmaceutically acceptable adjuvants that do not promote conversion of more than 0.2% by weight of the gabapentin to its corresponding lactam form when stored at 25.degree. C. and an atmospheric humidity of 50% for one year.
Dependencies are inferred from the claim text.