| HS Code | 714867 |
| Product Name | Fluocinolone Acetonide Ointment Veterinary Grade API |
| Active Ingredient | Fluocinolone Acetonide |
| Grade | Veterinary Grade |
| Cas Number | 67-73-2 |
| Molecular Formula | C24H30F2O6 |
| Molecular Weight | 452.49 g/mol |
| Appearance | White or almost white crystalline powder |
| Solubility | Practically insoluble in water; freely soluble in acetone; sparingly soluble in ethanol |
| Melting Point | 270-274°C |
| Purity Assay Hplc | 97.0% to 102.0% calculated on anhydrous basis |
| Suitable Dosage Forms | Ointment; Tablets; Injections; Capsules; Powders; Granules; Premix; Solutions |
| Storage Conditions | Store in well-closed containers, protected from light, in a cool and dry place |
As an accredited Fluocinolone Acetonide Ointment Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Packaged in sealed, light-protected containers with tamper-evident seals; quantity 25 kg per drum, labeled for veterinary pharmaceutical use. |
| Container Loading (20′ FCL) | One 20-foot FCL loaded with sealed drums/cartons of Fluocinolone Acetonide veterinary-grade API, secured, ventilated, and protected from moisture. |
| Shipping | Ship as a controlled, non-hazardous pharmaceutical API in sealed, light-resistant containers. Maintain cool, dry conditions, avoiding extreme temperatures. Use sturdy export-grade packaging with proper labeling, MSDS, and certificates of analysis. Comply with veterinary drug shipping regulations and customs documentation for international transport. |
| Storage | Store Fluocinolone Acetonide veterinary-grade API in a tightly sealed, light-resistant container, in a cool, dry, well-ventilated area between 20–25°C. Protect from moisture, heat, and direct sunlight. Keep away from oxidizing agents and incompatible materials. Maintain container integrity after each use. Follow established veterinary pharmaceutical storage guidelines and local regulations for safe handling and disposal. |
| Shelf Life | Shelf life is typically 24 months when stored properly in sealed, light-resistant containers at controlled room temperature. |
Because fluocinolone acetonide is practically insoluble in water and susceptible to alkaline hydrolysis, ointment manufacturing avoids aqueous phase addition entirely. The micronized drug substance is levigated in a portion of light mineral oil or propylene glycol before being diluted into a blend of white petrolatum and lanolin alcohol absorption base. Working concentrations in companion animal dermatology are generally maintained between 0.01% w/w and 0.025% w/w; above this range the risk of local skin atrophy and systemic absorption increases without a documented therapeutic advantage. The API particle size is controlled by laser diffraction to a D90 of ≤15 µm under ISO 13320-1:2020 before incorporation. A three-roll mill with water-cooled rollers is operated at a front roller gap of 25–50 µm for two passes; this reduces agglomerates and prevents heat-induced degradation of the 17α,21-acetonide group. Residual moisture is kept below 0.5% w/w and water activity is held below 0.6 to maintain the anhydrous state required for chemical stability. Batch release tests include appearance, assay, related substances by HPLC, and viscosity. Microbial limits are assessed under USP<61> and USP<62>; preservation efficacy for multi-use tubes follows USP<51> when a preservative is present. Commercial production is subject to 21 CFR 211, while extemporaneous compounding falls under USP<795>. The terminal pack is a 15 g or 30 g collapsible aluminum tube with an epoxy-phenolic internal liner and a white polyethylene spiked cap. This configuration is limited to topical use; ophthalmic administration or application to broken skin is not supported because published data for this specific veterinary ointment configuration is limited.
For canine otitis externa, fluocinolone acetonide is compounded into a low-water or anhydrous otic vehicle together with an aminoglycoside or polypeptide antibacterial and an azole antifungal. The corticosteroid concentration is kept between 0.005% w/w and 0.01% w/w to reduce the probability of epithelial thinning and delayed tympanic membrane healing while still providing anti-inflammatory activity. The limiting process factor is not the high-shear equipment but the aggregation tendency of the micronized API when the wetting agent is added too rapidly. The drug substance is first dispersed in polysorbate 80 at 0.05% w/v with slow agitation for 5 min before the bulk vehicle is introduced. A rotor-stator homogenizer with a 10 mm generator is then operated at 5,000 rpm for 10 min. Final particle size measured under ISO 13320-1:2020 should show D50 <3 µm, D90 <10 µm, and span <1.6. Sodium carboxymethyl cellulose at 0.3% w/v is used as the suspending agent; the final viscosity is adjusted to 40–80 mPa·s at 25°C using a rotational viscometer per ASTM D2196-20. The pH is buffered with citrate to 4.5–5.2 because alkaline conditions accelerate degradation of the acetonide ring. Benzalkonium chloride at 0.02% w/v is incompatible with carbomer 934P; if a carbomer vehicle is selected, phenethyl alcohol at 0.5% v/v is substituted. Release testing follows USP<795> for nonsterile compounded preparations, and packaging is in 10 mL or 20 mL amber low-density polyethylene dropper bottles with child-resistant caps.
When the intended tablet dose falls below 0.2 mg, direct compression is rejected because segregation of the active from lactose monohydrate produces out-of-specification content uniformity. Fluocinolone acetonide is preblended with lactose monohydrate NF at a 1:10 ratio in a twin-shell blender at 15 rpm for 10 min, followed by a 1:100 dilution. Wet granulation is performed with povidone K-30 at 3% w/v in an isopropyl alcohol–water vehicle; the wet mass is passed through a 1.0 mm screen and dried in a fluid bed dryer with inlet air at 50°C ± 2°C until loss on drying is <1.5% w/w. The dried granules are milled through a 0.8 mm screen and blended with microcrystalline cellulose PH-102, croscarmellose sodium 2.0% w/w, and magnesium stearate 0.5% w/w. Compression on a 16-station rotary tablet press is conducted at 4–8 kN; target hardness is 4–8 kp and friability is ≤1.0%. For capsules, the same granule is filled into size 3 or 4 hydroxypropyl methylcellulose capsules to a weight variance of ±5%. Dose strength is typically 0.05 mg to 0.2 mg fluocinolone acetonide per unit, intended for feline glucocorticoid-responsive conditions. The release profile is tested by reversed-phase HPLC with UV detection at 254 nm under USP<621>.
For cGMP production, the following release matrix applies:
| Test | Method / Standard | Acceptance criterion |
|---|---|---|
| Assay by HPLC | USP<621> / Ph. Eur. 2.2.29 | 90.0–110.0% label claim |
| Content uniformity | USP<905> | Acceptance value ≤15 |
| Dissolution | USP<711>, Apparatus 2, 50 rpm, 900 mL 0.1 N HCl with 0.1% sodium lauryl sulfate | Q ≥ 80% at 30 min |
| Friability | USP<1216> | ≤1.0% |
| Microbial limits | USP<61>/<62> | TAMC ≤102 CFU/g, TYMC ≤101 CFU/g, E. coli absent |
Storage is controlled at 20–25°C with protection from light; moisture ingress beyond 2.0% w/w in the finished bulk is a rejection condition. The terminal container is an amber high-density polyethylene bottle with an induction-sealed polyethylene liner and 1 g silica gel desiccant.
In equine non-food practice, intralesional or intra-articular injection is prepared as an aseptic suspension because fluocinolone acetonide is practically insoluble in aqueous solution and cannot be sterilized by terminal membrane filtration. The working concentration is generally limited to 0.1 mg/mL to 2 mg/mL to control local tissue exposure; published data for this specific veterinary configuration is limited, and the exact dosing range is confirmed by the attending veterinarian. The API must be sterile micronized material with D90 <5 µm and span <1.5 under ISO 13320-1:2020. The vehicle contains sodium carboxymethylcellulose 0.5% w/v, polysorbate 80 0.1% w/v, sodium chloride 0.9% w/v, and citrate buffer adjusted to pH 5.0. Viscosity is adjusted to 5–15 mPa·s at 25°C via ASTM D2196-20 so that the product resuspends after storage but remains injectable through a 23-gauge needle. Aseptic compounding is conducted in an ISO 14644-1:2015 Class 5 environment; all components are sterile and the final suspension is filled into amber Type I borosilicate glass vials with chlorobutyl stoppers and aluminum flip-off seals. Terminal moist heat at 121°C for 15 min is not applied unless specific thermal stability data for the formulation batch demonstrate no degradation. Batch release includes sterility under USP<71>, bacterial endotoxins under USP<85>, and subvisible particulate matter under USP<788>. The aseptic process is validated with media fills at a frequency not exceeding 6 months; environmental monitoring requires viable and non-viable particle counts consistent with the cleanroom class.
For oral solution reconstitution and non-food animal hospital-dilution premixes, dry granulation is preferred over stock aqueous compounding because the 17α,21-acetonide hydrolysis rate increases in bulk aqueous media. The dry powder is prepared by geometric dilution of fluocinolone acetonide with lactose monohydrate NF from 1:10 to 1:100 or 1:1,000 depending on the requested dose batch size. A twin-shell blender at 12 rpm for 30 min provides homogeneity; the blend is then passed through a 60 mesh sieve to break up soft agglomerates. If granulation is needed for flowability, roller compaction at 2–4 MPa is applied and the compacted material is milled through a 0.8 mm screen. Loss on drying after compaction is controlled to <1.0% w/w; powder flow is characterized by Carr index and Hausner ratio, with a target Carr index of ≤25. The finished powder or granule is packed in 1 kg and 5 kg high-density polyethylene jars with double polyethylene liners; a desiccant is inserted when water activity exceeds 0.45. For premix use, the label states the concentration as fluocinolone acetonide per gram of vehicle and the complete dilution steps required before administration. Use in food-producing animal feed is not supported because residue depletion data for edible tissues are absent. Cross-contamination control requires dedicated or validated cleaning lines, with rinse water and swab limits established by the manufacturer; published data for this specific veterinary premix configuration is limited.
Fluocinolone acetonide is practically insoluble in water; a clear oral solution requires either a high-concentration co-solvent system or an inclusion complex. A formulation containing 20% w/v hydroxypropyl-β-cyclodextrin and 10% v/v propylene glycol can support a drug concentration of 0.1 mg/mL at final pH 4.0–5.0; published data for this specific veterinary configuration is limited, and solubility should be confirmed by phase-solubility testing before scale-up. The cyclodextrin is first dissolved in purified water at 40°C under low-shear agitation; fluocinolone acetonide is pre-wet with propylene glycol and added with continuous stirring for 60 min. The sodium citrate buffer is then added to maintain pH 4.5, because higher pH accelerates the cleavage of the acetonide group. The solution is clarified through a 0.22 µm polyethersulfone membrane filter; the filter is pre-wetted to reduce adsorption losses, and the first 10 mL of filtrate is discarded. Recovery is assessed by HPLC to confirm that the membrane does not remove more than 5% of the labeled amount. The final product is filled into amber polyethylene terephthalate bottles with child-resistant closures and a calibrated oral dosing syringe. Storage is recommended at 2–8°C; if no preservative is added, the in-use period is limited to 14 days under refrigeration. This solution form is intended for companion animal oral administration where a compounded liquid is required; it is not a commercial licensed product and must be prepared under USP<795> unless manufactured under 21 CFR 211.
Competitive Fluocinolone Acetonide Ointment Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
Fluocinolone acetonide, CAS 67-73-2, is a synthetic fluorinated corticosteroid with the molecular formula C24H30F2O6 and relative molecular mass 452.49 g/mol. The veterinary-grade active pharmaceutical ingredient is supplied for incorporation into tablets, injections, capsules, powders, granules, premix, and solutions. In this context, the grade designation does not identify a single physical form; it defines an API with documented particle-size distribution, residual solvent profile, elemental impurity control, microbial quality, and, where applicable, bacterial endotoxin content appropriate to the intended route of administration. The molecule contains 6α- and 9α-fluoro substituents and a 16α,17α-isopropylidene acetonide group, which together modify glucocorticoid receptor binding, metabolic stability, and lipophilicity relative to non-fluorinated corticosteroids.
The compound is practically insoluble in water and dissolves in organic solvents such as ethanol, propylene glycol, and dichloromethane; aqueous formulations therefore require non-aqueous cosolvents, cyclodextrin complexation, or suspension engineering. The API is intended for the preparation of veterinary products used in inflammatory and immune-mediated dermatological, otic, and ophthalmic conditions, but the final route, species, and dose determine the applicable control strategy. Replacement of triamcinolone acetonide or dexamethasone with fluocinolone acetonide in an existing formulation is not a direct weight-for-weight substitution and must be addressed through route-specific development.
Fluocinolone acetonide is subject to monograph requirements in the Ph. Eur. and USP; the veterinary-grade material is released against a specification that combines these requirements with route-specific additional controls. The assay acceptance window of 97.0%–102.0% on the dried basis is typical for the substance, and related substances are controlled by high-performance liquid chromatography with the total impurity limit generally not exceeding 2.0%. Loss on drying is limited to 1.0%, and sulfated ash is limited to 0.1% unless a supplier-specific tighter limit is registered. Residual solvent control follows VICH GL18 rather than a single universal list because the solvent set depends on the synthesis and crystallization route.
| Parameter | Release Limit | Method / Standard |
|---|---|---|
| Appearance | White or almost white crystalline powder | Visual examination, supplier monograph |
| Identification | Infrared spectrum consistent with reference standard; HPLC retention time consistent | Ph. Eur. 2.2.24; USP <197> |
| Assay on dried basis | 97.0%–102.0% | HPLC with UV detection |
| Related substances | Total ≤ 2.0%; individual specified impurities at monograph limits | HPLC area normalization or external standard |
| Loss on drying | ≤ 1.0% | Ph. Eur. 2.2.32 |
| Sulfated ash | ≤ 0.1% | Ph. Eur. 2.4.14 |
| Residual solvents | Class 2 solvents limited per VICH GL18; for example, methanol ≤ 3000 ppm, dichloromethane ≤ 600 ppm where used | Headspace gas chromatography |
| Elemental impurities | Per ICH Q3D; risk-based limits for Pd, Pt, Ni, As, Cd, Pb, Hg | ICP-MS |
| Microbial enumeration | TAMC ≤ 10² CFU/g; TYMC ≤ 10¹ CFU/g; absence of Escherichia coli | Ph. Eur. 2.6.12, 2.6.13 |
| Bacterial endotoxins | Specified for injections and solutions; limit based on maximum dose and route | Ph. Eur. 2.6.14 |
For powder, granule, and premix applications, microbial enumeration limits may be adjusted according to the finished product specification and target species. Where the API is intended for aseptic processing of injectable suspensions or ophthalmic products, additional internal controls for bioburden, sub-visible particles, and container closure integrity are applied to the API or the intermediate slurry.
The chemical identity of human-use and veterinary-use fluocinolone acetonide is identical; therefore the distinction lies in the control strategy and documentation package. A veterinary-grade API for tablets, injections, capsules, powders, granules, premix, and solutions is released with a supply-chain declaration that addresses transmissible spongiform encephalopathy risk, and the residual solvent and elemental impurity assessments are aligned with VICH GL18 and ICH Q3D rather than only human-pharmaceutical regional requirements. For injectable and otic preparations, endotoxin and bioburden limits become release parameters, whereas some human compounding APIs may not carry those guarantees. In addition, particle-size distribution is usually not a pharmacopoeial general monograph parameter; therefore a human-grade API intended for topical ointment may be micronized without evidence of suitability for suspension injection syringeability or low-dose oral premix homogeneity.
Particle-size distribution is the principal physical attribute separating acceptable veterinary-grade lots from material that will fail during manufacture. Laser diffraction per ISO 13320 is used to define the volume median diameter and the upper decile. A micronized grade intended for ointments, injectable suspensions, and ophthalmic suspension vehicles is usually specified with a volume median diameter below 10 µm and a D90 value controlled to prevent syringe needle occlusion, corneal irritation, and grittiness in semi-solid bases. For tablets, capsules, powders, granules, and premix, a coarser unmicronized material may be acceptable if blend uniformity, content uniformity, and dissolution or drug release are demonstrated by the finished-product specification. However, low-dose tableting and premix operations present content uniformity risks because the API is often present at less than 0.5% by weight; direct compression without pre-blending or trituration can produce superpotent and subpotent units.
Micronization by spiral jet mill under nitrogen introduces amorphous surface domains and electrostatic charge. These changes can produce agglomerates after storage, particularly when relative humidity exceeds 50%. Processing areas for micronized fluocinolone acetonide are therefore maintained below 50% RH, and product-contact surfaces are grounded to dissipate static charge. If the API is stored in partially opened containers or exposed to ambient humidity above 60% RH, particle-size retesting by wet laser diffraction per ISO 13320 is required before batch release for suspension products.
For injectable suspension manufacturing, the micronized API is dispersed in an aqueous vehicle using a high-shear rotor-stator mixer followed by high-pressure homogenization. Homogenization pressure and number of passes are specified to break agglomerates without raising the bulk temperature enough to accelerate crystal growth. Terminal steam sterilization is usually avoided because the heat cycle may alter crystal size distribution; aseptic processing with sterile API or sterile-filtered vehicle is the standard route. The API must therefore meet the agreed bioburden and endotoxin limits before entry into the aseptic core, and the finished suspension is tested for sub-visible particles according to Ph. Eur. 2.9.19 or USP <788> as appropriate.
In ointment manufacturing, the API is levigated with a small portion of liquid paraffin or mineral oil before incorporation into the petrolatum base; this prevents the formation of drug-rich agglomerates that would fail the particle-size test for semisolids. Oleaginous vehicles such as white petrolatum provide occlusive effects, but the API must be dispersed evenly to avoid high-concentration domains. The acetonide group reduces aqueous solubility and can slow release from anhydrous bases; this prolonged dermal residence requires in vitro release testing during development rather than reliance on visual homogeneity.
| Dosage form | Critical API property | Principal processing risk | Control method / standard |
|---|---|---|---|
| Tablets | Particle-size distribution, bulk density | Content uniformity failure at low dose; compaction variability | USP <905>; Ph. Eur. 2.9.40; dissolution USP <711> |
| Capsules | Bulk density, flow, electrostatic charge | Segregation during encapsulation; API adhesion to capsule shells | Blend uniformity sampling; USP <905> |
| Injections / solutions | Solubility in cosolvent system, endotoxin | Precipitation on aqueous dilution; filter membrane adsorption | Sub-visible particle testing Ph. Eur. 2.9.19; USP <788>; Ph. Eur. 2.6.14 |
| Injections / suspensions | Micronized D50, D90, crystal habit | Needle occlusion; particle growth during autoclaving or freeze-thaw | Wet laser diffraction ISO 13320; syringeability test; sedimentation volume |
| Powders / granules / premix | Carrier adsorption, homogeneity | Superpotent pockets in low-inclusion premix; cross-contamination | Assay uniformity; USP <905> or equivalent blend uniformity |
| Ointments | D90 in semi-solid base, crystalline form | Grittiness; drug-rich agglomerates; polymorph conversion during levigation | Microscopy; particle-size test for semisolids; identity Ph. Eur. 2.2.24 |
These route-dependent constraints show that the same API lot can be suitable for tablets and premix but unsuitable for injectable suspensions if the particle-size distribution is not within the micronized range and if endotoxin control has not been included. Conversely, a micronized sterile API may be necessary for ophthalmic preparations but may create flow and dusting problems in low-dose tablet manufacture. Therefore, the supplier must be informed of the intended dosage form at the time of qualification, and separate API grades should be established where a single physical form cannot meet all route requirements.
Solution formulations require a different control logic. Fluocinolone acetonide is practically insoluble in water; finished solutions therefore rely on non-aqueous cosolvents such as ethanol, propylene glycol, and polyethylene glycol mixtures. Aqueous dilution of these concentrates can cause precipitation unless the cosolvent ratio is held above the solubility threshold determined for the specific pH and temperature. Membrane filtration of dilute fluocinolone acetonide solutions may be affected by adsorption onto filter materials; filter compatibility and drug recovery must be verified under the actual filtration time and pressure. Preservative compatibility must also be confirmed because benzalkonium chloride and other cationic preservatives can interact with anionic excipients in aqueous vehicles and alter solution clarity or antimicrobial activity.
Fluocinolone acetonide and triamcinolone acetonide are both acetonide derivatives of fluorinated corticosteroids, but the additional 6α-fluoro substituent in fluocinolone acetonide changes receptor binding and lipophilicity. Topical corticosteroid potency classifications place fluocinolone acetonide in the high-potency group, whereas triamcinolone acetonide is generally classified in the medium-to-high range. This difference means that formulators cannot simply replace triamcinolone acetonide with fluocinolone acetonide on a milligram-for-milligram basis. The concentration and dosing interval must be re-justified for the target species and lesion type. In otic and ophthalmic veterinary preparations, fluocinolone acetonide may permit a lower nominal concentration for equivalent anti-inflammatory response, but the vehicle must be re-engineered because the two APIs do not share identical solubility profiles in non-aqueous bases. Stability studies with the finished ointment or solution must be repeated because oxidative and hydrolytic degradation kinetics differ between the two molecules.
Compared with dexamethasone and betamethasone, fluocinolone acetonide has higher topical potency per unit mass but is not used interchangeably in systemic veterinary protocols. Dexamethasone and betamethasone are more commonly formulated as phosphate or acetate salts for injectable solutions, whereas fluocinolone acetonide is usually presented as a micronized suspension or semi-solid dosage form. The acetonide group imparts greater lipophilicity and a longer dermal residence time, but it also complicates aqueous solution development and increases the risk of precipitation when cosolvent systems are diluted with saline or water for injection. Published data for this specific configuration is limited, and finished-product stability data under VICH GL3 are required to justify any interchange.
The residual solvent profile of a fluocinolone acetonide veterinary-grade API depends on the synthesis and crystallization route used by the manufacturer. Suppliers using ethanol or ethyl acetate as final crystallization solvents will produce a different residual solvent chromatogram than those using dichloromethane or methanol earlier in the synthesis. Limits for class 2 solvents are taken from VICH GL18; for example, methanol is limited to 3000 ppm and dichloromethane to 600 ppm when those solvents are declared. A certificate of analysis that lists only “complies with residual solvent requirements” without naming the solvent set is insufficient for route-specific quality risk assessment because solvent residues influence granulation, drying, and packaging interactions.
Elemental impurities are controlled using the risk-based approach of ICH Q3D. If the synthesis uses a palladium or platinum catalyst, the corresponding metal residue must be validated by a purge study or controlled by a confirmatory ICP-MS method. This is particularly relevant for APIs intended for injectable or otic use in small companion animals, where cumulative metal exposure from repeated dosing must be considered in the veterinary medicinal product dossier. Stress studies on fluocinolone acetonide show sensitivity to strongly acidic and alkaline conditions, with hydrolysis of the acetonide and ester linkages producing the corresponding diol and related fluorinated derivatives. Oxidative degradation can occur in the presence of peroxides; therefore antioxidants such as butylated hydroxytoluene may be added only after compatibility with the API and container closure system has been demonstrated. For solution products, pH selection is formulation-specific and must be justified by stress stability data; no universal pH range applies to all veterinary formulations.
Storage and packaging of the veterinary-grade API are specified to protect the micronized solid from moisture and light. Double polyethylene liners inside an aluminum foil or HDPE drum are standard, with storage at 25 °C ± 2 °C and 60% RH ± 5% for climate zone II stability studies. Re-test dating is assigned from long-term and accelerated stability data generated under VICH GL3 and VICH GL5 if photostability is relevant; the assigned retest interval applies only to unopened containers stored in the original closure. After first opening, the material should be re-evaluated for moisture uptake and particle-size shift before use in a production batch.
