Gabapentin Enacarbil API is a synthetic prodrug of gabapentin developed to provide improved and more consistent absorption after oral administration. It is an orally active gabapentinoid and is converted to gabapentin by enzymes in the gastrointestinal tract and other tissues.
Gabapentin Enacarbil is used in pharmaceutical formulations for the treatment of moderate-to-severe primary restless legs syndrome (RLS) and postherpetic neuralgia (PHN) in adults. It is marketed in the United States under the brand name Horizant.
The compound is chemically designated as (1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexaneacetic acid) and has the molecular formula C₁₆H₂₇NO₆ with a molecular weight of 329.39 g/mol.
Gabapentin Enacarbil is a racemic mixture consisting of the R- and S-enantiomers. The drug substance is supplied as a white to off-white crystalline solid.
| Property | Value |
|---|---|
| API Name | Gabapentin Enacarbil |
| CAS Number | 478296-72-9 |
| Molecular Formula | C₁₆H₂₇NO₆ |
| Molecular Weight | 329.39 g/mol |
| Chemical Class | Gabapentinoid / Gabapentin Prodrug |
| Pharmacological Class | Alpha-2-delta Ligand |
| Form | Racemic mixture |
| Appearance | White to off-white crystalline solid |
| Active Metabolite | Gabapentin |
Gabapentin Enacarbil is a prodrug of gabapentin. Following oral administration, it is converted to gabapentin, which binds to the α2δ subunit of voltage-gated calcium channels in the central nervous system.
This interaction is believed to reduce excitatory neurotransmitter release and contributes to its therapeutic effects in conditions such as restless legs syndrome and postherpetic neuralgia.
Gabapentin Enacarbil itself does not appear to have direct pharmacological activity at the α2δ receptor comparable to gabapentin; its therapeutic activity results primarily from conversion to gabapentin.
Gabapentin Enacarbil is used as an active pharmaceutical ingredient in formulations for:
The approved extended-release tablets are available in strengths including 300 mg and 600 mg of gabapentin enacarbil.
Gabapentin Enacarbil was developed to overcome some of the absorption limitations associated with gabapentin.
It is transported through the intestinal wall using high-capacity nutrient transport mechanisms, resulting in more dose-proportional exposure compared with gabapentin.
After absorption, enzymatic hydrolysis converts Gabapentin Enacarbil to gabapentin, which is responsible for the principal pharmacological activity.
| 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% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |
| Melting Point | Approximately 100–105°C |