Roflumilast API is a selective phosphodiesterase-4 (PDE4) inhibitor belonging to the benzamide class of pharmaceutical compounds. It is a non-steroidal anti-inflammatory active pharmaceutical ingredient used in respiratory and dermatological formulations. Roflumilast acts by inhibiting PDE4, an enzyme involved in the metabolism of intracellular cyclic adenosine monophosphate (cAMP), thereby influencing inflammatory signaling.
Roflumilast is supplied as a chemically defined small-molecule API and is used in both oral and topical pharmaceutical products. Regulatory documentation identifies the substance as a white to off-white crystalline or powder material.
Roflumilast is chemically identified as 3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide. The API has the molecular formula C17H14Cl2F2N2O3 and a molecular weight of approximately 403.21 g/mol. Its CAS Registry Number is 162401-32-3.
The molecule contains a substituted benzamide structure together with dichloropyridine, difluoromethoxy and cyclopropylmethoxy groups. Its chemical structure contributes to its lipophilic character and low aqueous solubility.
Roflumilast is a synthetic, non-steroidal PDE4 inhibitor. It is characterized by a substituted aromatic benzamide framework containing chlorine and fluorine atoms. PubChem reports a calculated XLogP3-AA value of approximately 4.6, reflecting the compound's relatively lipophilic nature.
Regulatory chemistry assessments describe roflumilast drug substance as a white to off-white powder. It is practically insoluble in water and hexane, sparingly soluble in ethanol and freely soluble in acetone. The FDA has also characterized the drug substance as non-hygroscopic, with a polymorph assessment identifying a single polymorphic form in the reviewed material.
Roflumilast API is used in pharmaceutical formulations designed to provide PDE4-mediated anti-inflammatory activity.
Its established pharmaceutical applications include:
The specific indication depends on the dosage form, strength and regulatory authorization of the finished pharmaceutical product.
Roflumilast selectively inhibits phosphodiesterase-4 (PDE4). PDE4 is an important enzyme responsible for the metabolism of intracellular cyclic AMP. Inhibition of PDE4 by roflumilast increases intracellular cAMP levels and modulates inflammatory signaling.
Roflumilast is metabolized to roflumilast N-oxide, which is also pharmacologically active and contributes to PDE4 inhibition. The FDA describes both roflumilast and roflumilast N-oxide as PDE4 inhibitors that promote accumulation of intracellular cAMP.
Quality control of Roflumilast API involves comprehensive testing appropriate for a chemically defined small-molecule pharmaceutical ingredient. Typical analytical evaluation includes identity, assay, related substances, residual solvents, water content, residue on ignition or sulfated ash where applicable, elemental impurities and physical characteristics.
Identity may be established using spectroscopic and chromatographic techniques, while assay and related substances are generally evaluated using validated chromatographic methods. Particle-size distribution and solid-state characteristics may also be evaluated where required by the intended formulation and regulatory specification.
The FDA chemistry assessment for an approved roflumilast product states that detailed drug-substance CMC information was reviewed through the relevant Drug Master File.
Importantly, an FDA review specifically stated that no USP monograph had been established for roflumilast at the time of that assessment. Therefore, universal USP numerical release limits should not be assumed for the API.
Roflumilast API is manufactured through controlled chemical synthesis followed by purification and isolation of the active pharmaceutical ingredient. Manufacturing controls are designed to maintain chemical purity, control process-related impurities and residual solvents, and ensure consistent physical properties.
A pharmaceutical-grade manufacturing process should incorporate appropriate in-process controls, validated analytical methods, controlled environmental conditions and documented batch-release procedures. Solid-state and particle characteristics may also be controlled where they can affect downstream pharmaceutical processing or product performance.
Roflumilast is generally described as a white to off-white crystalline powder or powder. It has low aqueous solubility and is comparatively lipophilic.
Published and regulatory sources report:
Roflumilast API should be packed in suitable pharmaceutical-grade containers that protect the material from contamination, moisture and unsuitable environmental exposure. Packaging should be selected according to the manufacturer's validated stability data and applicable regulatory requirements.
Storage conditions should be established from stability studies and the approved API specification. Containers should remain tightly closed when not in use, with appropriate controls for temperature, humidity and light where required.
A pharmaceutical Roflumilast API manufacturer can provide appropriate quality and regulatory documentation according to the customer's requirements, which may include:
Documentation availability is subject to the applicable product specification, manufacturing site and regulatory requirements.
Choosing a qualified Roflumilast API manufacturer in India can support pharmaceutical companies requiring consistent-quality active ingredient for respiratory and topical pharmaceutical development.
A reliable manufacturing partner should provide:
Roflumilast API requires appropriate control of chemical purity, physical characteristics and low aqueous solubility-related processing considerations. A quality-focused manufacturing approach can therefore support reliable downstream formulation and pharmaceutical production.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| pH (1% Solution) | 6.5 |
| Melting Point | Approx. 158° |