Stable pharmaceutical composition of 3-(hydroxymethyl)-5,5-diphe

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514358, A61K 31135

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active

049258605

ABSTRACT:
Described is a stable pharmaceutical composition of 3-(hydroxymethyl-5,5-diphenylhydantoin disodium phosphate ester, the prodrug of 5,5-diphenylhydantoin (phenytoin) a commonly used drug for the treatment and management of epilepsy and other types of convulsive states. It has been found that degradation of the prodrug to phenytoin can be controlled by controlling the pH of the composition. Controlling the pH to between 8.3 to 9.4 results in the production of diphenylglycinamide as the primary degradant and minimization of degradation to phenytoin. If the pH is maintained at a lower or higher value, then the degradation pattern changes, with earlier than expected product failure.

REFERENCES:
patent: 4260769 (1981-04-01), Stella
Varia et al., "Phenytoin Prodrug IV: Hydrolysis of Various 3-(Hydroxymethyl)Phenytoin Esters", Journal of Pharmaceutical Sciences, vol. 73, No. 8, Aug. 1984, (pp. 1068-1090).

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