Phenytoin Sodium is the sodium salt of Phenytoin and is an established anticonvulsant active pharmaceutical ingredient belonging to the hydantoin class. It is also known as 5,5-Diphenylhydantoin Sodium and Diphenylhydantoin Sodium. The API has the molecular formula C15H11N2NaO2 and a molecular weight of 274.25 g/mol. Its CAS Number is 630-93-3. Phenytoin Sodium is chemically different from Phenytoin Base, which has CAS Number 57-41-0 and a molecular weight of 252.27 g/mol.
Phenytoin Sodium is described in the International Pharmacopoeia as a white, odourless powder. It is soluble in water, producing a slightly turbid solution because of partial hydrolysis, soluble in ethanol, and practically insoluble in ether. The International Pharmacopoeia classifies Phenytoin Sodium as an anticonvulsant pharmaceutical substance. It is somewhat hygroscopic and can gradually absorb carbon dioxide when exposed to air, making appropriate packaging and storage important.
The substance should be kept in a tightly closed container. Controlled storage helps protect the material from moisture and environmental exposure during pharmaceutical manufacturing, testing and handling.
Phenytoin Sodium is widely recognized for its anticonvulsant activity. Phenytoin stabilizes neuronal membranes by affecting voltage-dependent sodium channels and reducing repetitive neuronal firing. It has been used in pharmaceutical preparations for the management of seizures and is also associated with anti-arrhythmic activity.
The sodium salt is particularly important in pharmaceutical formulation because its physicochemical properties differ from those of the free Phenytoin Base. This distinction is important when selecting an API for formulation development, analytical testing and finished pharmaceutical manufacturing.
Phenytoin Sodium is used as an active ingredient in pharmaceutical dosage forms, including conventional oral preparations and parenteral products. For parenteral applications, additional requirements such as bacterial endotoxin control apply under the applicable pharmacopoeial standards. The International Pharmacopoeia specifies a bacterial endotoxin limit of not more than 0.3 IU per mg for Phenytoin Sodium intended for parenteral use.
Pharmacopoeial quality control of Phenytoin Sodium includes identity, assay, loss on drying and elemental impurity testing. The current USP-NF preview defines Phenytoin Sodium as containing not less than 98.0% and not more than 102.0% of C15H11N2NaO2, calculated on the dried basis.
The International Pharmacopoeia provides a different assay range of 98.5%–101.0%, also calculated with reference to the dried substance. Its assay is performed by non-aqueous titration with perchloric acid, with each mL of 0.1 mol/L perchloric acid equivalent to 27.43 mg of Phenytoin Sodium.
For a CMS specification, the applicable pharmacopoeial standard should therefore be identified rather than combining USP and International Pharmacopoeia assay limits into one specification.
Phenytoin Sodium quality assessment includes control of related substances and degradation products. USP identifies Phenytoin Related Compound A and Phenytoin Related Compound B as reference standards for the monograph.
An accessible USP monograph reproduction specifies limits of not more than 0.9% each for Phenytoin Related Compound A and Phenytoin Related Compound B and not more than 0.1% for Benzophenone. The same monograph describes chromatographic determination of other impurities. These values should be treated as the cited USP monograph limits rather than transferred to unrelated dosage-form specifications.
The International Pharmacopoeia specifies loss on drying of not more than 30 mg/g, equivalent to 3.0%, after drying to constant weight at 105°C. It also specifies heavy metals at not more than 10 μg/g, equivalent to 10 ppm.
The International Pharmacopoeia additionally describes an identity approach involving extraction followed by infrared examination and characteristic sodium identification tests. The melting temperature of the residue after acidification and extraction is reported at about 295°C, corresponding to Phenytoin.
Phenytoin Sodium should be maintained in tightly closed containers and protected from moisture and environmental exposure. Because the material is somewhat hygroscopic and can absorb carbon dioxide from air, appropriate packaging and controlled handling are important for maintaining pharmaceutical quality.
Phenytoin Sodium remains an important pharmaceutical API for anticonvulsant formulations. Reliable control of identity, assay, moisture, impurities and elemental contaminants supports consistent quality throughout pharmaceutical development and manufacturing.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 3.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |