Phenytoin Capsules

General Notices

Phenytoin Capsules from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable.

Action and use

Antiepileptic.

Definition

Phenytoin Capsules contain Phenytoin Sodium.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of phenytoin sodium, C15H11N2NaO2

92.5 to 107.5% of the stated amount.

Identification

A. Centrifuge the precipitated mixture obtained in test B, dissolve the residue in methanol, evaporate and dry at 105° for 30 minutes. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of phenytoin (RS 272).
B. Shake a quantity of the contents of the capsules containing 0.5 g of Phenytoin Sodium with 10 mL of water and filter. The filtrate yields a white precipitate on the addition of 2m hydrochloric acid.
C. To 0.1 g of the residue obtained in test A add 0.5 mL of 1m sodium hydroxide, 10 mL of a 10% w/v solution of pyridine and 1 mL of copper sulfate-pyridine reagent and allow to stand for 10 minutes. A blue precipitate is produced.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Shake a quantity of the contents of the capsules containing 0.20 g of Phenytoin Sodium with 5 mL of methanol, warm on a water bath with shaking and filter.
(2) Dilute 1 volume of solution (1) to 200 volumes with methanol.
(3) 0.020% w/v of benzophenone in methanol.
chromatographic conditions
(a) Use as the coating a suitable silica gel containing a fluorescent indicator with an optimal intensity at 254 nm (Merck silica gel 60 F254 is suitable).
(b) Use the mobile phase as described below. Pre-wash the plate with methanol and allow it to dry in air before use.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in a current of cold air for 2 minutes before development of the chromatograms. After removal of the plate, dry it at 80° for 5 minutes and examine under ultraviolet light (254 nm).
mobile phase

10 volumes of 13.5m ammonia, 45 volumes of chloroform and 45 volumes of propan-2-ol.

limits

In the chromatogram obtained with solution (1):

any spot corresponding to benzophenone is not more intense than the spot in the chromatogram obtained with solution (3) (0.5%);

any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).

Assay

Shake a quantity of the mixed contents of 20 capsules containing 0.25 g of Phenytoin Sodium with 40 mL of 0.01m sodium hydroxide for 5 minutes and dilute to 50 mL with 0.01m sodium hydroxide. Centrifuge, acidify 25 mL of the clear liquid with 10 mL of 0.1m hydrochloric acid and extract with successive quantities of 50, 40 and 25 mL of ether. Wash the combined extracts with 10 mL of water, evaporate to dryness and dry the residue at 105°. Dissolve in 50 mL of anhydrous pyridine and carry out Method II for non-aqueous titration, Appendix VIII A, using 0.1m tetrabutylammonium hydroxide VS as titrant and a 0.3% w/v solution of thymol blue in anhydrous pyridine as indicator. Each mL of 0.1m tetrabutylammonium hydroxide VS is equivalent to 27.43 mg of C15H11N2NaO2.