| HS Code | 827566 |
| Product Name | Febuxostat Pharma Grade API |
| Api Type | Febuxostat Active Pharmaceutical Ingredient |
| Drug Class | Xanthine Oxidase Inhibitor |
| Cas Number | 144060-53-7 |
| Molecular Formula | C16H16N2O3S |
| Molecular Weight | 316.38 g/mol |
| Physical Form | White to off-white crystalline powder |
| Solubility | Practically insoluble in water, slightly soluble in methanol, soluble in dimethylformamide |
| Dosage Forms | Tablet, Capsule, Granule, Injection |
| Route Of Administration | Oral and Injectable |
| Purity | 99.0% to 101.0% on dried basis |
| Storage Conditions | Store in a cool, dry place below 25°C, protected from light and moisture |
| Shelf Life | 24 months when stored under recommended conditions |
| Pharmacopoeial Compliance | USP, EP, or IP grade available |
As an accredited Febuxostat Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Febuxostat Pharma Grade API packed in double polythene-lined HDPE drums, 25 kg net per drum, for oral and injectable dosage forms. |
| Container Loading (20′ FCL) | Description: One 20′ FCL container loaded with palletized, secured drums of Febuxostat Pharma Grade API, suitable for oral and injectable formulations. |
| Shipping | Febuxostat Pharma Grade API ships in sealed, inert containers with desiccants, protected from light and moisture. Transportation follows cold-chain or controlled room temperature guidelines as required. Hazard-compliant labeling, tamper-evident packaging, and full documentation ensure safe, regulatory-aligned delivery for oral and injectable pharmaceutical manufacturing. |
| Storage | Store in a tightly closed container in a cool, dry place, protected from light, moisture, and strong oxidizing agents. Maintain room temperature below 25°C, away from direct sunlight. Ensure packaging remains sealed when not in use. This API is intended for pharmaceutical formulation; handle with appropriate safety precautions to preserve stability and efficacy. |
| Shelf Life | Shelf Life: 24 months from manufacture when stored in original sealed container, below 25°C, protected from moisture and light. |
Febuxostat is a xanthine oxidase inhibitor with low aqueous solubility across the physiological pH range, and high-shear wet granulation is used to improve compactibility, bulk flow, and dose uniformity in immediate-release tablet manufacture. The API addition ratio for wet-massed tablet cores is 12–25 wt%; a 40 mg dose in a 250 mg core corresponds to 16.0 wt%, while an 80 mg dose in a 400 mg core corresponds to 20.0 wt%. The granulating fluid typically contains 5–8 wt% polyvinylpyrrolidone K30 and 0.05–0.20 wt% sodium lauryl sulfate in purified water, with lactose monohydrate, microcrystalline cellulose PH102, and croscarmellose sodium as the primary intragranular diluents and disintegrant. Process control uses a high-shear granulator with impeller speed 200–600 rpm and chopper speed 1500–3000 rpm; the endpoint is determined by torque rise or power consumption rather than fixed mixing time. Wet mass is dried in a fluid-bed dryer at 55–65 °C inlet air temperature to a loss-on-drying target of 1.5–2.5 wt%, milled through a 1.0 mm screen, and lubricated with 1.0–2.0 wt% sodium stearyl fumarate before compression. Compliance anchors include ICH Q3C for residual solvents, ICH Q3D for elemental impurities, USP <905> for content uniformity, and USP <711> dissolution testing with a suprafacial dissolution medium such as pH 6.8 phosphate buffer containing 0.5% sodium lauryl sulfate. Terminal product type is film-coated immediate-release tablets at 40 mg and 80 mg strengths. A documented production-scale failure mode is over-granulation beyond the torque plateau, which creates dense intragranular matrix structures that retard wetting and slow dissolution, particularly for hydrophobic API fractions above 20 wt%.
Dry granulation lines that supply febuxostat-loaded hard capsules often replace aqueous wet massing when moisture exposure must be minimized or when a high drug load requires a smaller final fill weight. The intragranular API addition is 20–40 wt%; a 40 mg capsule filled to 160 mg contains 25.0 wt%, while an 80 mg capsule filled to 200 mg contains 40.0 wt%. The blend contains microcrystalline cellulose PH301 at 30–50 wt%, anhydrous lactose at 15–30 wt%, crospovidone at 2–6 wt%, and sodium stearyl fumarate at 0.5–1.5 wt%. In a roller compactor, the powder is densified between counter-rotating rolls with a roll gap of 2–4 mm, roll pressure of 3–8 kN/cm roll width, and roll speed of 3–10 rpm; the resulting ribbon solid fraction is controlled between 0.55 and 0.70. Ribbon-milled granules are passed through a conical mill fitted with a 1.0 mm screen at 800–1200 rpm, producing a granule D50 of 250–500 µm suitable for consistent encapsulation on dosator or dosing-disc machines. Capsule fill weight is controlled within ±5% by USP <905>, and dissolution is checked by USP <711> in a medium appropriate to the capsule shell and formulation surfactant content. Terminal product type is hard gelatin or HPMC capsule shells containing 40 mg or 80 mg febuxostat. Process failures observed at production scale include ribbon sheeting at low roll pressure, excessive fines generation, and work-hardening of the regranulated material when ribbon solid fraction exceeds 0.70, which reduces compactibility and increases capsule fill variability.
| Dry granulation parameter | Range | Reference designation |
|---|---|---|
| Intragranular API load | 20–40 wt% | Master formula record |
| Roll gap | 2–4 mm | Roller compactor setup |
| Ribbon-milled granule D50 | 250–500 µm | Laser diffraction |
| Capsule fill weight variation | Within ±5% | USP <905> |
| Dissolution medium | pH 6.8 with 0.5% sodium lauryl sulfate | USP <711> |
Orally disintegrating tablet manufacture for febuxostat differs from standard compression because the formulation must simultaneously satisfy rapid disintegration in the oral cavity and maintain friability below 1.0 wt% during packaging and transport. The API addition ratio is 10–30 wt% for direct-compression ODT formulations, while lyophilised wafer formulations reduce the API mass fraction to 5–15 wt% because the freeze-dried matrix is highly porous and therefore more sensitive to drug-induced collapse. In direct-compression ODTs, co-processed mannitol at 40–70 wt%, crospovidone at 4–10 wt%, sucralose at 0.3–0.8 wt%, and peppermint or orange flavour at 0.5–1.5 wt% are tabletted at compression forces of 5–15 kN, producing hardness values of 20–40 N and tablet diameters that remain within tooling limits for 20 mg, 40 mg, and 80 mg strengths. Disintegration is evaluated using Ph. Eur. 2.9.1 or USP <701> with a target of no more than 30 s in 5 mL of aqueous medium at 37 °C. If freeze-dried ODT technology is used, the liquid filling suspension or solution is dosed into preformed blister pockets and lyophilised at shelf temperatures between −40 °C and −25 °C; the resulting wafer is highly friable and requires peel-lid packaging with desiccant. Residual solvent control follows ICH Q3C, and elemental impurity control follows ICH Q3D. Terminal product type is orally disintegrating tablets for dysphagic or elderly patients requiring rapid administration without water. Published bioequivalence data for this specific febuxostat configuration are limited, so formulation screening requires forced degradation and transportation stress testing before commercial scale-up.
In parenteral development, febuxostat is solubilized by combined pH adjustment and inclusion complexation because the free acid form is practically insoluble in neutral aqueous media. A candidate compounded solution at 2–10 mg/mL can be prepared by adding the API to water for injection containing sulfobutyl ether β-cyclodextrin at 70–85 wt% of the dry cake, mannitol at 5–15 wt%, and sodium phosphate buffer at 1–3 wt%; the lyophilised cake contains API at 6–12 wt%. The solution is adjusted to pH 6.8–7.4 after complete solubilisation, passed through a 0.22 µm PVDF or PES membrane, filled aseptically, and lyophilised at shelf temperatures between −40 °C and −25 °C. This presentation is not a licensed commercial product in all jurisdictions, and published data for this specific configuration are limited; each batch is screened for particulate matter, reconstitution time, and stopper compatibility. Terminal product type is a sterile vial for reconstitution or a ready-to-use infusion solution for hospital administration. Compliance anchors include 21 CFR 211 for aseptic processing, USP <1> for injections, ICH Q3C for residual solvents, ICH Q3D for parenteral daily exposure limits, and USP <85> for bacterial endotoxin testing where applicable.
| Sterile manufacturing control point | Operating range | Reference designation |
|---|---|---|
| Sterile filtration membrane | 0.22 µm PVDF or PES | USP <1> |
| Lyophilisation shelf temperature | −40 °C to −25 °C | Freeze-dryer recipe |
| Reconstituted solution pH | 6.8–7.4 | Ph. Eur. 2.2.3 |
| Residual solvents | Limits for class 1, 2, and 3 solvents | ICH Q3C |
| Elemental impurities | Parenteral daily exposure limits | ICH Q3D |
When febuxostat is processed into oral granules as a terminal sachet presentation or as a patient-specific dose-titration intermediate, the API addition ratio is set at 10–20 wt% relative to total granule mass. The granule matrix contains sorbitol or mannitol at 50–70 wt%, maize starch or pregelatinized starch at 10–20 wt%, hydroxypropyl cellulose binder at 2–5 wt%, and sodium lauryl sulfate at 0.2–1.0 wt% to improve wetting of the low-solubility API. Granulation is conducted in a fluid-bed granulator with inlet air temperature 50–65 °C, spray rate 5–15 mL/min/kg of dry charge, and atomisation pressure 1.0–2.5 bar. After drying to a loss-on-drying value of 1.0–2.0 wt%, the granules are sieved through 500–1000 µm screens to remove oversize and fines before filling into sachets or dose cups. Bulk density is maintained between 0.50 g/mL and 0.75 g/mL, with a Carr index below 20% as a flow indicator for volumetric filling. Compliance anchors for granule terminal product include Ph. Eur. 2.9.36 or USP <1174> for powder flow, ICH Q3C for residual solvents, ICH Q3D for elemental impurities, and USP <711> dissolution testing after dispensation in water. Terminal product type is oral granules in sachet or unit-dose cup format, allowing dose adjustment in patients with renal or hepatic impairment where dose strength beyond the fixed tablet increment may be required.
When direct compression is evaluated for febuxostat, particle engineering of the API and co-processed filler selection become the controlling variables because unprocessed API lots may exhibit cohesive flow and low compactibility. The API addition ratio is 10–30 wt%, with co-processed silicified microcrystalline cellulose/lactose at 40–70 wt%, crospovidone at 3–6 wt%, magnesium stearate at 0.5–1.0 wt%, and colloidal silicon dioxide at 0.2–0.5 wt% as glidant. Blending is performed in a low-shear bin blender at 10–20 rpm for 15 min, with the lubricant added in the final 3–5 min to avoid over-lubrication. Compression is run on a rotary tablet press at forces of 10–20 kN, producing hardness values of 50–70 N and tablet thickness of 3–4 mm for 40 mg and 80 mg cores. Content uniformity is verified by USP <905>, and dissolution is assessed by USP <711> using a solubility-discriminating medium. Terminal product type is immediate-release tablet cores intended for subsequent aqueous or organic film coating. Direct compression is not suitable for all API lots above 30 wt% loading unless the API has been pre-processed by spray drying or co-milling to reduce its cohesive fraction and improve bulk density.
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Febuxostat Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is a non-purine selective xanthine oxidase inhibitor supplied as a white to off-white crystalline powder for formulation into immediate-release tablets, hard gelatin or hydroxypropyl methylcellulose capsules, granules for oral suspension or sachet filling, and sterile injectable preparations. The active substance is identified by CAS registry number 144060-53-7, molecular formula C16H16N2O3S, and molecular mass 316.37 g/mol. The product is offered in two process-ready grades: a micronized oral-grade powder with controlled particle size for tablet, capsule, and granule manufacture, and a bioburden-controlled injectable-grade powder intended for sterile manufacturing after dissolution and filtration. Published BCS classification places febuxostat in Class II; permeability is high, but aqueous solubility is pH-dependent and low across the physiological gastrointestinal range, making dissolution of the drug substance the rate-limiting step for oral absorption. The material is manufactured under ICH Q7 GMP for active pharmaceutical ingredients and released against a specification aligned with current pharmacopoeial monograph requirements where adopted.
Because febuxostat is dissolution-limited, the specific surface area of the drug substance directly governs intrinsic dissolution rate. Micronization is not merely particle reduction; it sets the solid-liquid interfacial area available during the compendial dissolution test and subsequent gastrointestinal release. Particle size distribution is determined by laser diffraction per USP <429>, with a typical micronized oral grade controlled to a D90 of ≤20 µm and a D50 in the 5–15 µm range. The acceptance criterion is justified by the finished product dissolution profile rather than by bulk powder behavior alone. For granule and capsule presentations, larger particles may be acceptable when the formulation includes a wetting agent such as sodium lauryl sulfate or a polymeric solubility enhancer; selection is confirmed by comparative dissolution testing per USP <711> using the regulatory method for the intended reference product. Flow properties are measured by bulk density and tapped density per USP <616>, with Hausner ratio and Carr index reported on the certificate of analysis because particle morphology can shift tablet weight uniformity under high-speed compression. Powder flow through an orifice is evaluated using USP <1174>; for direct compression, colloidal silicon dioxide is commonly integrated at levels below 0.5% w/w to avoid dissolution slowdown while maintaining ejection force stability.
Production-scale batch records from rotary tablet presses operating in the 60–100 rpm range indicate that tablet sticking and picking occur when residual moisture in the API exceeds 1.0% w/w; the oral-grade specification therefore includes water content not more than 1.0% by Karl Fischer titration per USP <921>. For wet granulation, a twin-screw granulator with an L/D ratio of 20:1 or a high-shear granulator with an impeller speed of 200–500 rpm is used; liquid-to-solids ratio is controlled within narrow limits because the low aqueous solubility of febuxostat can produce non-uniform binder distribution and subsequent tablet hardness variability. Granules are dried in a fluid-bed dryer with inlet air temperature not exceeding 60 °C to avoid amorphous content generation; the amorphous fraction is monitored by X-ray powder diffractometry per USP <941> or by modulated differential scanning calorimetry to ensure that recrystallization during storage does not reduce dissolution. Compression force is adjusted to achieve tablet tensile strength between 1.0 MPa and 2.0 MPa; lower values risk tablet capping, while higher values may extend disintegration time and delay release.
Granule presentations for oral suspension are manufactured with a target sieve fraction between 150 µm and 850 µm; particle size distribution is checked by analytical sieving per USP <786>. Granule flow and angle of repose are evaluated because sachet filling machines require consistent fill weight at speeds above 60 sachets/min; too high a fine fraction leads to dust and underweight filling, while coarse granules slow dissolution after reconstitution. The API is incorporated in the dry mix or in a binder solution after pre-suspension in purified water, with pH adjustment evaluated through forced degradation studies to limit chemical degradation. Capsule filling is performed on dosator or tamping-pin machines; because febuxostat is low-density and micronized, the powder bed may require pre-compression or the addition of a densifier to achieve consistent plug formation. Empty capsule shell selection depends on moisture sensitivity; hard gelatin shells are not used when the fill formulation contains deliquescent excipients. The resulting capsules are tested for content uniformity per USP <905> and dissolution per USP <711>; assay by HPLC per USP <621> is used for release.
| Parameter | Acceptance criterion | Test method/standard |
|---|---|---|
| Identification by infrared absorption | Corresponds to reference spectrum | USP <197> |
| Assay on dried basis | 98.0–102.0% | HPLC per USP <621> |
| Related substances | Any unspecified impurity ≤0.10%; total impurities ≤1.0% | HPLC per USP <621> |
| Water content | ≤1.0% | USP <921> Karl Fischer |
| Residue on ignition | ≤0.1% | USP <281> |
| Residual solvents | Conforms to ICH Q3C limits | USP <467> |
| Elemental impurities | Conforms to ICH Q3D limits | USP <232>/<233> |
| Particle size distribution | Report value; micronized grade D90 ≤20 µm | USP <429> |
| Bulk density / tapped density | Report value | USP <616> |
| Endotoxin, injectable grade | Calculated limit per USP <85> | USP <85> |
Each batch is accompanied by a certificate of analysis reporting residual solvents by headspace gas chromatography per USP <467> and elemental impurities by inductively coupled plasma mass spectrometry per USP <232>/<233>. Limits are assigned by ICH Q3D according to the intended route of administration; for injectable grades, the risk assessment also includes chromium, nickel, and molybdenum because stainless steel contact during micronization and filtration can contribute extractables. The API is packaged in double low-density polyethylene bags within a sealed aluminum foil laminate, with a retest period established under ICH Q1A conditions; ongoing stability samples are stored at 25 °C/60% RH and 40 °C/75% RH.
For injectable presentations, the finished product is prepared by dissolving or dispersing the API in a sterile aqueous vehicle prior to membrane filtration. Endotoxin burden is controlled by kinetic chromogenic Limulus amebocyte lysate testing per USP <85>; the acceptance limit is calculated as K/M, where K is 5 EU/kg and M is the maximum bolus dose in mg/kg for the intended product. Bioburden in the pre-filtration solution is maintained at ≤10 CFU/100 mL, and filter validation is conducted using Brevundimonas diminuta per ASTM F838. The finished injection is tested for subvisible particulate matter per USP <788> Method 1 and for visible particulates per USP <790>. Because febuxostat is a weak acid with pH-dependent solubility, injectable formulation requires pH adjustment into the pharmaceutically acceptable range and may include a co-solvent or cyclodextrin; published data for specific injectable configurations is limited, and no ready-to-use injectable formulation is implied or registered by this API supply.
Febuxostat differs from allopurinol in structure, metabolic fate, and renal elimination. Febuxostat is a non-purine xanthine oxidase inhibitor containing a thiazole carboxylate pharmacophore; allopurinol is a purine analogue that undergoes rapid metabolism to oxypurinol, which mediates most of its urate-lowering activity. Published in vitro studies report that febuxostat has higher potency for human liver xanthine oxidase than allopurinol and oxypurinol, but absolute IC50 values vary with assay substrate and enzyme source; the clinical significance is established through serum urate lowering rather than isolated enzyme potency. Febuxostat is cleared primarily by hepatic metabolism through uridine diphosphate glucuronosyltransferase and cytochrome P450 oxidation, with limited renal elimination of the unchanged molecule; allopurinol and oxypurinol depend on renal excretion, making allopurinol doses dependent on creatinine clearance. Regulatory labels for febuxostat include 40 mg and 80 mg film-coated tablets in the United States and 80 mg and 120 mg strengths in the European Union; allopurinol is marketed as 100 mg, 200 mg, and 300 mg tablets. Safety differentiation includes the cardiovascular mortality boxed warning added to the febuxostat label after the CARES postmarketing trial and the HLA-B*5801 screening recommendation for allopurinol in high-risk populations to reduce severe cutaneous adverse reactions. Febuxostat is generally not recommended as first-line therapy in current gout guidelines, but it is used when allopurinol is not tolerated or contraindicated.
| Attribute | Febuxostat | Allopurinol |
|---|---|---|
| Chemical class | Non-purine thiazole carboxylate | Purine analogue |
| Metabolic pathway | Hepatic UGT and CYP oxidation; limited renal elimination of unchanged drug | Rapid conversion to oxypurinol; renal excretion of oxypurinol |
| Renal dose adjustment | Not required for mild to moderate renal impairment in most approved labels | Dose adjustment required according to creatinine clearance |
| Approved oral tablet strengths | 40 mg, 80 mg US; 80 mg, 120 mg EU | 100 mg, 200 mg, 300 mg |
| HLA-B*5801 screening | Not required | Recommended before initiation in high-risk populations |
| Key safety warning | Boxed warning for cardiovascular mortality | Severe cutaneous adverse reactions and renal-function-dependent dosing |
Handling and containment practices for the micronized oral-grade powder require local exhaust ventilation or ventilated balance enclosures because low-micrometer particles remain airborne during dispensing. Occupational exposure limits are not harmonized globally; the material safety data sheet assigns a control band based on therapeutic potency and dustiness. For solid oral dosage form development, compatibility studies with common excipients are recommended before full formulation because the weakly acidic nature of febuxostat can affect salt formation and disintegration pH; published data for specific excipient incompatibilities is limited, and forced degradation studies are used to establish method specificity.
