Revefenacin is a synthetic long-acting muscarinic antagonist (LAMA) and anticholinergic bronchodilator developed for the maintenance treatment of chronic obstructive pulmonary disease (COPD). It is administered once daily by oral inhalation using a nebulizer. The FDA approved revefenacin in 2018 as the active pharmaceutical ingredient in YUPELRI inhalation solution.
Revefenacin is identified by CAS No. 864750-70-9, molecular formula C35H43N5O4, and molecular weight 597.7 g/mol according to PubChem; the FDA label reports a molecular weight of 597.76 g/mol.
Revefenacin is a small-molecule anticholinergic containing a biphenyl carbamate structure with two piperidine rings. FDA describes the drug substance as a white to off-white, achiral, crystalline powder. The approved active substance is the anhydrous free-base crystalline form, with FDA quality documentation identifying Form 1 as the thermodynamically most stable form.
The chemical name reported by FDA is:
1-(2-{4-[(4-carbamoylpiperidin-1-yl)methyl]-N-methylbenzamido}ethyl)piperidin-4-yl N-([1,1′-biphenyl]-2-yl)carbamate.
PubChem reports an exact mass of 597.33150487 Da, XLogP3-AA of 4.1, hydrogen-bond donor count of 2, hydrogen-bond acceptor count of 6, 11 rotatable bonds, and topological polar surface area of 108 Ų.
Revefenacin is indicated for the maintenance treatment of patients with COPD. It is not intended for treatment of acute bronchospasm or immediate relief of acute COPD symptoms.
The approved dosage is 175 mcg once daily, delivered by oral inhalation through a standard jet nebulizer with a mouthpiece. Each unit-dose vial contains 175 mcg of revefenacin in 3 mL of sterile aqueous solution.
As a LAMA, revefenacin provides prolonged bronchodilation and is designed for once-daily maintenance therapy.
Revefenacin is a muscarinic receptor antagonist. FDA pharmacology studies demonstrated activity at all five human muscarinic receptor subtypes, M1 through M5. Its bronchodilator effect in the airways is mediated primarily through inhibition of the M3 receptor on airway smooth muscle.
By blocking acetylcholine-mediated muscarinic signaling at airway smooth muscle, revefenacin reduces bronchoconstriction and promotes airway relaxation, producing sustained bronchodilation.
Its molecular design incorporates a metabolically labile region intended to promote systemic clearance while maintaining prolonged local pulmonary activity.
Quality control for Revefenacin API may include:
FDA quality documentation identifies the free base as an anhydrous crystalline and thermodynamically stable form, with Form 1 identified as the most thermodynamically stable crystalline form.
A universal current numerical API release specification for assay and individual impurities was not identified in the public authoritative sources reviewed. Therefore, unsupported numerical acceptance limits are not presented as universal specifications.
Revefenacin is a synthetic small-molecule API manufactured through controlled chemical synthesis followed by purification and crystallization/solid-state control.
The selected API form is an anhydrous crystalline free base, and control of solid-state properties is important because the FDA quality assessment specifically identifies the selected Form 1 crystal as the thermodynamically favorable form.
Manufacturing controls should address chemical identity, assay, related substances, residual solvents, elemental impurities, solid-state form, water content and stability.
The molecular and physicochemical values are supported by PubChem and FDA documentation. FDA describes the drug substance as slightly soluble in water and reports the finished inhalation solution at pH 5.0.
The approved YUPELRI formulation is supplied as 175 mcg/3 mL of sterile, clear, colorless aqueous solution in unit-dose low-density polyethylene (LDPE) vials. Each vial is individually overwrapped in a foil pouch.
The finished product is stored at 20–25°C, with permitted excursions from 15–30°C. The product should be protected from direct sunlight and excessive heat.
For bulk Revefenacin API, storage conditions should be established according to validated API stability data and the applicable manufacturer specification rather than automatically applying finished-product storage conditions.
Typical documentation for Revefenacin API may include:
A qualified Revefenacin API manufacturer in India should maintain robust controls over chemical synthesis, purification, crystalline form, impurity management and analytical testing.
Particular attention should be given to control of the anhydrous crystalline API form, related substances, residual solvents and solid-state characteristics to ensure consistent quality for inhalation pharmaceutical applications.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |