| HS Code | 264247 |
| Product Name | Ivermectin Ear Drops Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions |
| Product Type | Active Pharmaceutical Ingredient (API) |
| Grade | Veterinary Grade |
| Active Ingredient | Ivermectin |
| Cas Number | 70288-86-7 |
| Molecular Formula | C48H74O14 |
| Molecular Weight | 875.1 g/mol |
| Appearance | White to yellowish-white crystalline powder |
| Solubility | Practically insoluble in water; soluble in organic solvents such as methanol, ethanol, and ethyl acetate |
| Purity | Typically ≥ 98.0% (per certificate of analysis) |
| Melting Point | 155-162°C |
| Storage Conditions | Store in a cool, dry, well-ventilated area protected from light and moisture |
| Shelf Life | Generally 24-36 months when stored properly in the original sealed container |
| Dosage Forms | Suitable for tablets, injections, capsules, powders, granules, premix, solutions, and ear drops |
| Target Species | Cattle, sheep, goats, pigs, horses, dogs, cats, and poultry (veterinary use) |
| Therapeutic Use | Antiparasitic treatment against endoparasites and ectoparasites in animals |
As an accredited Ivermectin Ear Drops 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-resistant containers to protect Ivermectin API purity. Quantity: 25 kg per drum, veterinary grade for multiple formulations. |
| Container Loading (20′ FCL) | One 20′ FCL of Ivermectin veterinary API, packed in sealed drums/pallets, secured and ventilated for safe transport. |
| Shipping | Ivermectin veterinary grade API is shipped in sealed, moisture-proof containers to ensure stability and purity. Transport complies with global pharmaceutical regulations, with full documentation and tracking available. Delivered worldwide by air or sea in secure packaging. Store in a cool, dry place away from direct sunlight. No special temperature-controlled handling required. |
| Storage | Store in a cool, dry, well-ventilated area at controlled room temperature, away from direct sunlight, heat, and moisture. Keep in a tightly closed, original container. Ensure area is clearly labelled and inaccessible to children and animals. Avoid contact with strong oxidizers. Use appropriate personal protective equipment when handling. |
| Shelf Life | Typically 2-3 years when stored in a cool, dry place, protected from light and moisture, in sealed containers. |
A non-aqueous injectable solution based on 10 mg/mL ivermectin in 40% v/v glycerol formal and 60% v/v propylene glycol is prepared under vacuum-assisted mixing because the macrocyclic lactone ring is susceptible to hydrolytic opening at the oleandrosyl glycosidic bonds when residual water is present. The API is dispersed in the glycerol formal fraction at 35–40°C using a side-entry rotor-stator homogenizer until a clear, amber solution is obtained; the propylene glycol fraction is then charged and the bulk is cooled to 20–25°C for sterile filtration through a 0.22 µm PVDF or nylon membrane. A nitrogen blanket is maintained in the receiving vessel because oxidative degradation at the conjugated diene system is accelerated by dissolved oxygen. The final solution is filled into 50 mL, 200 mL, and 500 mL amber Type II glass vials without terminal autoclaving; fill volume allowances follow USP <1>, and particulate matter is controlled by USP <788> for injectable products. For cattle, the approved subcutaneous dose is 200 µg/kg, equivalent to 1 mL per 50 kg body weight at 10 mg/mL; for swine, the subcutaneous dose is 300 µg/kg in the neck. Residual water is measured by Karl Fischer titration and controlled below the process-validation limit; on production lines where relative humidity exceeds 60%, transfer lines are purged with dry nitrogen. Viscosity is measured with a Brookfield rotational viscometer using an LV-2 spindle at 60 rpm to set filling-nozzle back pressure. Endotoxin limits are validated by USP <85>, and residual solvent declarations follow VICH GL18 / ICH Q3C. The principal batch failure on production-scale filling lines is moisture ingress through unsealed transfer lines; such ingress produces a polar degradant peak by HPLC with UV detection at 245 nm, so relative humidity in the compounding suite is controlled below 60% during open-charge operations.
In sheep and goat drench manufacturing, the low aqueous solubility of ivermectin—approximately 4 µg/mL at 25°C—requires a co-solvent system rather than a simple water solution. A typical oral drench is compounded to 0.8 mg/mL ivermectin in propylene glycol, benzyl alcohol, and purified water, with polysorbate 80 added as a wetting agent; the benzyl alcohol fraction is maintained at the minimum validated concentration, typically 1.5–2.0% v/v, to avoid excessive salivation at the point of drenching. The API is dissolved in the co-solvent phase at 40°C, the water phase is added under a high-shear disperser, and the bulk is cooled to 20–25°C before filtration through a 50 µm polypropylene bag filter. The oral solution is packed in 1 L, 2.5 L, and 5 L high-density polyethylene backpacks with calibrated drench gun connectors. Sheep are dosed orally at 0.2 mg/kg, which corresponds to 1 mL per 4 kg body weight at 0.8 mg/mL. Bioburden testing follows USP <61> and USP <62>; the acceptance limit for total aerobic microbial count is set at 10² CFU/mL with absence of Escherichia coli and Salmonella. An amber pack is used because ivermectin is UV-labile; the main process failure is precipitation of the active during bulk cooling if the polysorbate 80 content drops below the validated ratio. The finished drench is a clear, slightly viscous solution with a sharp aromatic odour from benzyl alcohol.
Dry blending of ivermectin at 0.6% w/w in a maize cob or soy hull carrier is used to produce a medicated premix for incorporation into swine complete feed. The API is milled through a 0.5 mm screen before charging to the ribbon mixer because particle-size differences between the API and carrier above 150 µm promote segregation during conveying. Mineral oil is sprayed at 0.5–1.0% w/w to bind fines and reduce dust aerosol. The mixer is operated at 60–70% net volume, with mixing time determined by sampling through the discharge gate; a coefficient of variation of ≤5% for three consecutive samples is the production acceptance criterion. Final premix is packed in 5 kg heat-sealed foil laminate bags with desiccant. Inclusion of 1 kg/t of a 0.6% w/w premix yields 6 mg/kg ivermectin in the finished feed; the dose is adjusted by the prescribing veterinarian according to species and production status. Carryover is controlled by sequencing the batch after a flush of ground maize, and dust extraction is locked to the mixer discharge. The regulatory basis in the EU is Regulation 2019/6 for veterinary medicinal products; in the US, medicated feed entries follow FDA 21 CFR Section 558 where the approved use is published. The main batch-to-batch variance source is residual moisture in the carrier; carrier lots above 12% w/w moisture are dried to below 8% w/w before blending to prevent caking and uneven distribution in the mixer.
When tablet potency drops to 68 µg or 136 µg per unit, direct addition of the API to a V-blender is not acceptable because the active content is less than 0.1% w/w of the finished tablet mass. The formulation is prepared by stagewise geometric dilution: an initial active-to-lactose monohydrate trituration at 1:10 is passed through a 250 µm stainless-steel sieve, then diluted stepwise to 1:100 and 1:1000 before final blending with microcrystalline cellulose, crospovidone, and magnesium stearate. Tablet weight is typically 300 mg, with the API present as a micronized grade having a D90 below 20 µm. The final blend is compressed on a rotary tablet press at 8–15 kN main compression force, and content uniformity is assessed by USP <905>; an acceptance value ≤15 is used as the release limit. The tablets are packaged in opaque PVC/aluminium blisters because ivermectin is light-sensitive, and dissolution testing follows USP <711> where a registered method exists. The main compression failure is lamination caused by excessive magnesium stearate; the lubricant is limited to 0.5% w/w and blended for not more than 5 min at 12 rpm. Low tablet hardness below 4 kp increases edge chipping on high-speed rotary presses, while hardness above 10 kp can delay disintegration if crospovidone is not distributed evenly. The chewable tablet may include a flavouring agent in the outer preblend; this component is added at the final lubrication step to avoid adsorption onto the micronized active.
| Dosage format | Typical concentration | Vehicle / carrier | Critical process control | Release or compliance reference |
|---|---|---|---|---|
| Injectable solution | 10 mg/mL | Glycerol formal / propylene glycol | 0.22 µm sterile filtration | USP <85>, USP <788> |
| Oral drench | 0.8 mg/mL | Propylene glycol / purified water | 10² CFU/mL bioburden | USP <61>, USP <62> |
| Feed premix | 0.6% w/w | Maize cob / soy hull | CV ≤5% in ribbon mixer | Regulation 2019/6 |
| Low-dose tablet | 68–272 µg/unit | Lactose / MCC | USP <905> AV ≤15 | USP <905>, USP <711> |
Compounded veterinary capsules with a label strength below 1 mg are prepared in a low-humidity room using lactose monohydrate or microcrystalline cellulose as filler. For a 3 mg capsule, the API is preblended with microcrystalline cellulose at 1:10, then further diluted to a final mix weight of 12 g per 100 capsule batch; methylparaben-free dry blends are used because water activity above 0.60 can destabilize the lactone ring. Gravity filling on a small semi-automatic capsule machine requires tight control of bulk density; the final mix is passed through a 600 µm sieve before encapsulation, and the tap density is checked by USP <616>. Gelatin capsules are stored in amber high-density polyethylene bottles with child-resistant caps. In veterinary practice, FDA 21 CFR Part 530 applies to extralabel use where the veterinarian determines that no approved animal formulation is clinically appropriate; the compounding standard in the US is USP <795> for nonsterile preparations. The major potency risk is segregation of micronized ivermectin during the final flow step; batch-to-batch weight sorting of filled capsules at ±5% of mean weight is used as an in-process control. Hard gelatin shells with low iron oxide pigment are preferred because high red iron oxide levels can accelerate photodegradation of ivermectin under direct light.
For drinking-water administration, granules are not true solutions; they are micellar dispersions in which ivermectin is solubilized by polysorbate 80 at a hydrophilic-lipophilic balance of 15. The granulation vehicle is prepared by dissolving ivermectin in propylene glycol, then adding polysorbate 80 and a water-soluble carrier such as lactose monohydrate or glucose monohydrate. The slurry is sprayed in a fluid-bed dryer with an inlet air temperature of 60°C and product temperature maintained between 35°C and 40°C; the resulting granules are sieved to 212–850 µm. Final granules are packed in 25 g and 100 g polyester/aluminium/polyethylene pouches under nitrogen. When reconstituted in cold water below 5°C, the system can bypass the micellar phase and form a coarse suspension with reduced dose uniformity; preparation instructions therefore specify room-temperature water and stirring for 60 s. The formulation is most suited to non-food-producing ornamental birds and captive ungulates where no statutory maximum residue limit applies; residue withdrawal planning under EU Regulation 2019/6 is required before use in food-producing animals. Operator exposure limits are managed by local exhaust ventilation and Class I disposable respiratory protection because airborne ivermectin during granule charging is a neurotoxic hazard. A moisture-barrier pouch is essential because the amorphous lactose carrier can absorb ambient moisture above 40% RH, leading to granule collapse and irregular reconstitution.
Otic drops for rabbit and guinea pig ear mite control formulated with veterinary-grade ivermectin are typically compounded as 0.1% w/v non-aqueous suspensions in propylene glycol with 0.5% w/v polysorbate 80 and 0.1% w/v benzyl alcohol. The API is deagglomerated by high-shear mixing and then passed through a colloid mill to reduce particle size to a D50 below 5 µm; this prevents needle-like crystals from abrading inflamed ear canal epithelium. A suspending grade of hydroxyethyl cellulose or PEG-40 castor oil may be added for yield stress. The suspension is filled into 10 mL or 20 mL low-density polyethylene dropper bottles with silicone rubber teats. The dosing frequency is set by the prescribing veterinarian; typical off-label protocols for Psoroptes cuniculi require one or two drops per ear, repeated after 14 days. The preparation is not sterile and is assigned a beyond-use date under USP <795>; because the non-aqueous vehicle supports only low microbial growth, it is not formulated with methylparaben. The product must be protected from light and stored below 30°C; low storage temperature can increase suspension viscosity and lead to non-uniform drop mass. A small package insert or label must state that the formulation is not approved for dogs, cats, or food-producing species unless specifically prescribed by a veterinarian.
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The product described as Ivermectin Ear Drops Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is an unformulated active pharmaceutical ingredient rather than a finished otic dosage form. The material is a white or almost white crystalline powder consisting principally of 22,23-dihydroavermectin B1a and 22,23-dihydroavermectin B1b, with CAS 70288-86-7. Compendial identity is established by liquid chromatography against the ivermectin chemical reference substance. The manufacturer’s lot designation is the only model identifier and is traceable through the certificate of analysis; no universal pharmacopoeial model number is assigned. Current Ph. Eur. and USP-NF monographs govern identification, assay, related substances, loss on drying, and sulfated ash; residual solvents are tested under Ph. Eur. 5.4 or USP <467>. The powder is released for further manufacturing into tablets, injections, capsules, powders, granules, premixes, solutions, and veterinary otic suspensions intended for ectoparasite management. Because the same crystalline API must perform across aqueous and non-aqueous matrices, the release specification is more restrictive than that of a single-route API in terms of residual-solvent control, particle-size documentation, and stability-indicating resolution of the B1a and B1b components. The API requires compounding or pharmaceutical manufacturing before administration.
The sum of 22,23-dihydroavermectin B1a and B1b is controlled between 95.0% and 102.0% on the anhydrous and solvent-free basis; the B1a component is not less than 90.0% of the ivermectin component. The ratio is monitored because the two homologues differ in the C25 substituent, and their relative proportion influences chromatographic response, potency per unit mass, and lipophilicity in the formulated product. In low-dose tablets containing as little as 68 µg per unit, a shift in the homologue ratio of even a few percent can change the labelled dose and push blend-uniformity acceptance outside USP <905> or Ph. Eur. 2.9.40. HPLC methods under the current monographs require baseline resolution of B1a and B1b; unresolved peak areas are rejected. The ratio also serves as a marker for incomplete hydrogenation from abamectin, because partially unsaturated impurities elute near the parent peaks and are controlled as related substances. Stability-indicating methods use the ratio to distinguish parent loss from epimerization or photodegradation in forced-degradation zones. Chromatographic detection is typically performed by ultraviolet absorption near 245 nm.
Table 1 summarizes the standard release profile used for bulk ivermectin intended for veterinary multi-route formulation. The values shown are widely recognized compendial acceptance limits; specific certificates of analysis may add route-specific tests such as particle-size distribution, endotoxin load, or microbiological bioburden.
| Parameter | Acceptance criterion | Reference or procedure |
| Appearance | White or almost white crystalline powder | Visual examination |
| Identification | Retention time matches Ivermectin CRS; B1a/B1b ratio | HPLC-UV at 245 nm |
| Assay, sum of B1a and B1b | 95.0–102.0% on anhydrous and solvent-free basis | Ph. Eur. liquid chromatography |
| 22,23-dihydroavermectin B1a | Not less than 90.0% | Ph. Eur. liquid chromatography |
| 22,23-dihydroavermectin B1b | Not more than 5.0% | Ph. Eur. liquid chromatography |
| Loss on drying | Not more than 1.0% | Ph. Eur. 2.2.32 |
| Sulfated ash | Not more than 0.1% | Ph. Eur. 2.4.14 |
| Residual solvents | Meets compendial limits | Ph. Eur. 5.4 / USP <467> |
| Particle-size distribution for otic or suspension use | D90 as agreed with the finished-product formulator | Laser diffraction under ISO 13320:2020 |
Release testing under ICH Q7 requires that any reprocessing of an out-of-specification batch be documented and that blending of batches with differing impurity profiles be avoided. Photoprotected storage in airtight containers is standard because the conjugated diene system absorbs ultraviolet radiation and generates degradation products that elute in the total-related-substances window. The powder is incompatible with strong oxidizing agents, hypochlorite-based sanitizers, and peroxides; contact with these species accelerates degradation of the macrocyclic lactone ring. Bulk hold in amber glass or opaque polyethylene-lined drums with a desiccant is used in production. Prolonged thermal stress during drying or milling is monitored by assay of retained samples; published data for a universal temperature limit are limited because the critical excursion depends on time, moisture content, and antioxidant presence.
For dry milling and low-dose blending, the material is frequently air-jet micronized to reduce median particle size. Particle-size distribution is measured by laser diffraction under ISO 13320:2020, and the selected D90 depends on the dosage form. Aqueous otic suspensions commonly require a D90 below 20 µm to limit gritty residue and sedimentation caking; dry blends for tablets and capsules may accept larger particles if dissolution is not rate-limiting. Published data for a single universal particle-size specification are limited because the optimum is route-dependent. Milled powder is hygroscopic after size reduction, so containers are sealed with desiccant when ambient relative humidity exceeds 60%. Geometric dilution is executed in a low-shear tumble blender or high-shear mixer before final blending; direct addition of the active powder to a full carrier charge produces superpotent and subpotent zones in low-dose formulations. Blend uniformity is checked by sampling at defined points according to Ph. Eur. 2.9.40 or USP <905>. The powder is practically insoluble in water but soluble in ethanol and propylene glycol; this solubility profile determines which wet-granulation binders can be used without precipitating the drug.
In veterinary otic formulations for Otodectes cynotis, ivermectin is presented as a suspension or non-aqueous solution because of its poor aqueous solubility. A registered feline otic suspension contains 0.01% w/v ivermectin and is administered at 0.5 mL per ear on some labels. The suspension vehicle requires a structured polymer network, typically microcrystalline cellulose or carbomer, combined with a nonionic wetting agent. Viscosity is balanced between dropper-tip flow and retention in the vertical ear canal; excessive yield stress traps air bubbles during vacuum-assisted filling and causes tube-weight variation. High-shear dispersion is used to deagglomerate the API before final vehicle addition. Preservative efficacy is tested according to Ph. Eur. 5.1.3 or USP <51>, and content uniformity in filled containers follows USP <905>. Because the otic suspension is not terminally sterilized, bioburden control and the absence of specified objectionable organisms are maintained during compounding. Stability in multidose containers after first opening is evaluated for preservative depletion and API oxidation; formulations with low antioxidant reserve may form colored degradation products at the dropper tip.
Injectable-grade solutions prepared from this API are typically non-aqueous because the substance has negligible solubility in water. Propylene glycol, glycerol formal, and benzyl alcohol are common cosolvents for registered parenteral products. The solution is clarified through a 0.2 µm sterilizing-grade filter; moist-heat sterilization is generally avoided for non-aqueous solvent systems when the drug shows thermal sensitivity. Sterility testing of the finished injectable is performed by Ph. Eur. 2.6.1 or USP <71>, and endotoxin content is limited under Ph. Eur. 2.6.14 or USP <85>. The API itself is not necessarily sterile; injectable formulators either purchase a low-endotoxin grade or perform depyrogenation and sterile filtration during compounding. Water contamination in non-aqueous vehicles can precipitate the drug or reduce chemical stability; production lines maintain low-humidity air handling and avoid aqueous wash residues. Elastomeric contact surfaces are evaluated for sorption at low drug concentrations, and stainless-steel transfer lines are preferred over untreated rubber hoses. For solutions containing ivermectin in propylene glycol, exposure to sunlight during bulk hold is controlled by amber vessels or opaque transfer piping.
Tableting and capsule filling with ivermectin are low-dose operations. Some labelled heartworm tablets contain as little as 68 µg of ivermectin per chewable unit, which is below the threshold where direct blending without staged geometric dilution can reliably pass USP <905>. The API is pre-blended with a free-flowing diluent of similar particle-size distribution, then discharged through a screen or cone mill to break soft agglomerates. Direct compression is used only when the pre-blend has a Hausner ratio below 1.25 and a Carr index below 25%; otherwise, roller compaction or wet granulation is introduced to densify the material and reduce segregation during hopper discharge. Segregation risk is assessed by sampling the hopper during tableting at start, middle, and end of run; assay values are compared with blend-uniformity data. Capsule filling on tamping-pin or auger machines requires controlled powder bed depth and rotating speed; over-tamping can increase local compaction and alter release from the capsule. Finished tablets and capsules are tested for dissolution by USP <711> or Ph. Eur. 2.9.3; dissolution media for this poorly water-soluble substance often include sodium lauryl sulfate above the critical micelle concentration. Granules for in-feed premix are manufactured by fluid-bed spray granulation, with inlet air temperature limited to avoid thermal assay loss. Premix concentration is verified by extraction and HPLC before release; a registered swine premix may contain 0.6% w/w ivermectin. For powders and granules, particle-size distribution and bulk density are recorded because both parameters affect feed mixing and final drug distribution in the ration.
The hydrogenation of abamectin at C22–C23 yields ivermectin and is the defining structural difference from abamectin. This modification reduces acute vertebrate neurotoxicity relative to abamectin while retaining activity against nematodes and arthropods. Selamectin is a semisynthetic avermectin with a different C5 substitution; its primary commercial use is topical spot-on therapy for fleas and heartworm, whereas the present API is produced for oral, injectable, otic, and in-feed routes. Moxidectin belongs to the milbemycin class and lacks the C13 disaccharide side chain carried by ivermectin; the resulting increase in lipophilicity is associated with a longer terminal half-life in some species. Eprinomectin is an ivermectin derivative with a C4″ amino substitution; it is preferred for lactating dairy cattle because the milk partition coefficient is low enough to avoid a milk discard period. Table 2 summarizes these route and species distinctions.
| API | Structural-pharmacologic distinction | Manufacturing or route implication |
| Ivermectin | 22,23-dihydroavermectin B1a/B1b | Broad route compatibility; low-dose oral solids and feed premixes; avoid high-dose use in MDR1-mutated breeds |
| Abamectin | Unsaturated C22–C23 precursor | Narrower vertebrate safety margin; less commonly selected where high systemic exposure occurs |
| Selamectin | Semisynthetic avermectin with C5 substitution | Topical spot-on orientation; formulation uses non-aqueous vehicles for dermal absorption |
| Moxidectin | Milbemycin lacking C13 disaccharide | Higher lipophilicity and longer half-life; used in cattle, sheep, and dogs under separate dosage regimens |
| Eprinomectin | C4″-epi-acetylamino derivative | Low milk partition coefficient; permits lactating dairy use without milk discard |
Selection among these APIs cannot be based solely on in vitro potency per milligram; formulators must consider species susceptibility to P-glycoprotein efflux, tissue residue depletion, and finished-product route. The present API is supplied as the multi-route bulk intermediate because its potency and stability profile allow a single chemical form to be partitioned into aqueous suspensions, non-aqueous parenteral solutions, low-dose oral solids, and feed premixes. The same property that supports broad use—high lipophilicity and low water solubility—also creates formulation constraints in aqueous vehicles. Manufacturing directions therefore specify co-solvent ratios, particle-size targets, and light-protected hold times; omission of these controls can produce precipitated injectable solutions, sedimented otic suspensions, or subpotent premix zones.
