Perampanel is a synthetic antiepileptic active pharmaceutical ingredient and a non-competitive antagonist of AMPA-type glutamate receptors. It is used in pharmaceutical formulations for the management of partial-onset seizures, including seizures that may occur with or without secondary generalized seizures. Perampanel is marketed under the brand name Fycompa and is classified pharmacologically as an anticonvulsant and AMPA receptor antagonist.
For pharmaceutical use, Perampanel is commonly represented as Perampanel hydrate (4:3), in which four molecules of anhydrous Perampanel are associated with three molecules of water. The Indian Pharmacopoeia Commission monograph identifies Perampanel as C23H15N3O·3/4H2O, with a molecular weight of 362.9 g/mol, and specifies that the material contains 98.0–102.0% of C23H15N3O calculated on the anhydrous basis.
Anhydrous Perampanel has the molecular formula C23H15N3O, CAS Number 380917-97-5, and molecular weight 349.39 g/mol. The FDA Global Substance Registration System confirms the formula, molecular weight and achiral nature of the anhydrous substance.
The pharmaceutical hydrate is a 4:3 Perampanel-water hydrate with the formula 4C23H15N3O·3H2O. FDA GSRS lists the molecular weight of the four-molecule hydrate representation as approximately 1451.59 g/mol, equivalent to 362.90 g/mol per Perampanel molecule including 0.75 equivalent of water.
The exact hydrate form is important for API documentation because the molecular weight and water content differ from those of anhydrous Perampanel. The FDA product label describes the active ingredient in FYCOMPA as Perampanel 4:3 hydrate, with a molecular formula of C23H15N3O·¾H2O and molecular weight 362.90 g/mol.
Perampanel is an antiepileptic drug that works through selective antagonism of AMPA receptors, which are ionotropic glutamate receptors involved in excitatory neurotransmission. Its pharmacological action distinguishes it from many conventional antiepileptic agents that act primarily through sodium or calcium channels or GABAergic mechanisms.
The active ingredient is used in oral pharmaceutical dosage forms. The FDA-approved product is available in tablet and oral-suspension formulations, with Perampanel present as the 4:3 hydrate.
The Indian Pharmacopoeia Commission (IPC) has published a Perampanel monograph specifying the hydrate form. The monograph describes Perampanel as a white to yellowish-white powder and requires identification by infrared absorption spectrophotometry and chromatographic comparison.
The official IPC assay requirement is 98.0–102.0% of C23H15N3O on the anhydrous basis. The assay is performed by liquid chromatography.
The related-substances method uses liquid chromatography with an octadecylsilane bonded silica column, a gradient mobile phase and UV detection at 290 nm. The monograph controls several named Perampanel impurities individually as well as other secondary peaks and total secondary peaks.
The IPC monograph specifies Perampanel impurities A, B, C and D at NMT 0.10% each, while Perampanel impurity E is NMT 0.15%. Any other secondary impurity is limited to NMT 0.10%, and the total of all secondary peaks is limited to NMT 0.50%. Peaks below 0.05% are disregarded under the specified procedure.
The chromatographic system is required to demonstrate a resolution of at least 1.5 between Perampanel and impurity F, column efficiency of at least 8000 theoretical plates, and a tailing factor of not more than 2.0.
Because the commercial pharmaceutical material is a hydrate, water content is an important quality attribute. The IPC monograph specifies 3.5–4.2% water, determined on a 20 mg sample. Sulphated ash is controlled at NMT 0.1%, while heavy metals comply with a 20 ppm limit.
The monograph also establishes microbiological quality requirements, including a total aerobic microbial count of NMT 1000 CFU/g, total combined yeasts and molds of NMT 100 CFU/g, and absence of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in the specified sample.
Perampanel should be protected from moisture. The IPC monograph specifies storage at a temperature not exceeding 30°C.
For API documentation, it is therefore important to clearly identify whether the material is being specified as anhydrous Perampanel or as the pharmaceutical 4:3 hydrate, and to report assay on the appropriate basis.
| 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 0.5% |
| Individual Impurity | NMT 0.10% |
| Water Content | 3.5–4.2% |