Phenytoin Base, also known as 5,5-Diphenylhydantoin or Diphenylhydantoin, is a hydantoin-class active pharmaceutical ingredient widely recognized for its anticonvulsant activity. The compound has the molecular formula C15H12N2O2 and a molecular weight of 252.27 g/mol. Its CAS Number is 57-41-0. Phenytoin Base is chemically distinct from Phenytoin Sodium, which is the sodium salt of the same active moiety and has a different molecular formula and molecular weight.
Phenytoin Base is a white crystalline powder with little or no odor. Pharmacopoeial references describe it as practically insoluble in water, sparingly soluble in ethanol and slightly soluble in ether. The International Pharmacopoeia identifies Phenytoin as an anticonvulsant pharmaceutical substance and specifies storage in a tightly closed container protected from light.
The compound has a high melting temperature of approximately 295°C. Historical pharmaceutical references report a melting range around 295–298°C, which is consistent with its highly crystalline structure.
Phenytoin is an established anticonvulsant active ingredient used in pharmaceutical formulations for seizure management. Its pharmacological action is associated with modulation of voltage-gated sodium channels, helping reduce abnormal neuronal electrical activity.
Phenytoin Base is also an important pharmaceutical raw material for manufacturers developing oral dosage forms and other finished pharmaceutical preparations. Depending on the formulation and regulatory market, manufacturers may use Phenytoin Base or convert/process the active moiety into an appropriate salt form such as Phenytoin Sodium.
Because Phenytoin Base has very low aqueous solubility, control of particle characteristics, crystallinity, purity and manufacturing consistency can be important during formulation development and pharmaceutical processing.
Quality control of Phenytoin Base includes identity testing, assay, loss on drying and organic impurity testing. The current USP 2025 monograph specifies an assay of 98.0%–102.0% on the dried basis. The USP method uses liquid chromatography with UV detection at 220 nm.
The USP monograph specifies Phenytoin Related Compound A at not more than 0.5%, Phenytoin Related Compound B at not more than 0.9%, Benzophenone at not more than 0.1%, any individual unspecified impurity at not more than 0.10%, and total impurities excluding Benzophenone at not more than 0.9%. Impurities below 0.05% are disregarded under the cited USP procedure.
The USP loss-on-drying requirement is not more than 1.0% after drying at 105°C for 4 hours. The International Pharmacopoeia similarly specifies loss on drying of not more than 10 mg/g, equivalent to 1.0%.
The International Pharmacopoeia provides an additional heavy-metals requirement of not more than 10 μg/g, equivalent to 10 ppm, and sulfated ash of not more than 1.0 mg/g, equivalent to 0.10%.
Phenytoin Base can be identified by infrared spectroscopy, with the sample spectrum compared against the appropriate Phenytoin reference standard. USP also uses chromatographic retention time as an identification criterion. The USP assay method employs a C18-type L1 column, UV detection at 220 nm, and a specified chromatographic system suitability requirement.
These analytical controls help verify identity, potency and impurity profile and are important for pharmaceutical manufacturing and quality assurance.
Phenytoin Base should be handled under appropriate pharmaceutical quality and safety procedures. The International Pharmacopoeia recommends storage in a tightly closed container protected from light. Manufacturers should establish appropriate packaging, environmental controls and handling procedures based on the applicable pharmacopoeial specification and product stability requirements.
Phenytoin Base API is therefore suitable for pharmaceutical development and manufacturing applications where controlled identity, assay, impurity profile and physical quality characteristics are required. Its established pharmacopoeial status and well-defined analytical profile make it a recognized pharmaceutical active ingredient for regulated production.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.10% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.90% |
| Melting Point | bout 295°C; reported reference range 295–298°C |