| HS Code | 550421 |
| Chemical Name | Levamisole hydrochloride |
| Cas Number | 16595-80-5 |
| Molecular Formula | C11H12N2S·HCl |
| Molecular Weight | 240.75 g/mol |
| Appearance | White or almost white crystalline powder |
| Solubility | Freely soluble in water, sparingly soluble in ethanol, practically insoluble in ether |
| Melting Point | 264°C to 268°C |
| Specific Rotation | Optically active, [α]D = -85° |
| Assay Content | 98.5% to 101.0% (on dried basis) |
| Ph Value | 3.0 to 4.5 (1% aqueous solution) |
| Storage Condition | Store in airtight container, protected from light |
As an accredited Levamisole 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 25 kg sealed drums with moisture-proof inner liner, clearly labeled for veterinary use, suitable for multiple dosage forms. |
| Container Loading (20′ FCL) | 20′ FCL container loading: Levamisole veterinary API in sealed drums/packaging, palletized, secured, labeled, and documented per shipment regulations. |
| Shipping | Levamisole Veterinary Grade API is shipped in sealed, moisture-proof, light-protected drums or bags, with tamper-evident packaging. Transport occurs in ventilated, dry containers, avoiding extreme temperatures. All shipments include Certificate of Analysis, Safety Data Sheet, and regulatory documentation. Proper handling and cold-chain protocols are available per destination requirements. |
| Storage | Store in a cool, dry, well-ventilated area away from direct sunlight and moisture. Keep container tightly closed and protected from physical damage. Avoid contact with oxidizing agents. Maintain appropriate temperature control, ideally below 25°C. Ensure segregation from food, feed, and non-veterinary products. Follow label instructions and keep out of reach of children and animals. |
| Shelf Life | Shelf life: 24 months from manufacture when stored unopened in original container in a cool, dry place. |
In direct compression of levamisole hydrochloride into a 300 mg ruminant tablet core, pre-sieving on a vibratory sieve fitted with a 710 µm stainless steel mesh is the first necessary operation. The needle-shaped crystal habit of the active pharmaceutical ingredient otherwise produces severe content non-uniformity during dry blending on high-speed rotary presses. The formulation stress is not the API loading but the excipient system: microcrystalline cellulose at 32–40% w/w provides compactibility, sodium starch glycolate at 2–4% w/w functions as the disintegrant, and magnesium stearate is limited to 0.25–0.35% w/w because its hydrophobic film prolongs wetting of the highly water-soluble drug. A typical core mass of 2.5 g places the API at 12.0% w/w; a smaller sheep tablet of 150 mg active strength and 1.2 g total core mass uses the same excipient ratio but requires tighter punch force control to prevent capping at the tablet edge. When wet granulation is substituted to improve powder flow for extended production campaigns, aqueous binder migration toward the drying bed surface redistributes levamisole hydrochloride and can generate assay variability exceeding 5% RSD across tray positions. This failure mode is controlled by using a low-shear planetary mixer with a binder addition endpoint of 8–10% w/w purified water and by drying in a fluid-bed dryer at an inlet air temperature not above 50°C. The dried granulate is milled through a 1.0 mm conical screen and lubricated in a bin blender for 10 min at 12 rpm. Release testing for such cores commonly follows USP <711> with paddle agitation at 50 rpm in 900 mL of 0.1 N hydrochloric acid at 37±0.5°C, although veterinary monographs may require a sinker for low-density formulations. Mass uniformity is assessed under Ph. Eur. 2.9.5 or USP <905>. Finished tablets are packed in PVC/aluminium blisters with a desiccant sachet because the disintegrant begins to lose functionality above 60% RH during tropical distribution.
A representative 20% w/v levamisole hydrochloride injection contains the active substance at 200 mg/mL, sodium metabisulfite at 0.10% w/v, disodium edetate at 0.01% w/v, benzyl alcohol at 1.0% v/v, and sufficient hydrochloric acid to bring the final pH to 4.0–4.5. The acidic pH is not arbitrary; it prevents precipitation of the poorly water-soluble free base that forms when the hydrochloride salt dissociates near neutral pH in weakly buffered aqueous systems. The product is filled into 50 mL Type II glass vials under nitrogen sparging because residual oxygen reacts with the metabisulfite antioxidant and produces turbidity during accelerated stability studies at 40°C/75% RH. Terminal autoclaving at 121°C for 15 min is possible at this pH but requires a cooling ramp below 3°C/min after peak temperature to avoid thermal spike at the vial wall. Many production lines instead use sterilising filtration through 0.22 µm polyvinylidene fluoride membranes and aseptic filling, because published data on the degradation kinetics of levamisole hydrochloride under saturated steam are limited.
Osmotic adjustment is a principal manufacturing bottleneck for this dosage form. A neat 20% w/v levamisole hydrochloride solution is markedly hypertonic relative to subcutaneous tissue, and the finished injection is therefore diluted with a sodium chloride vehicle to a measured osmolality near 280–300 mOsm/kg. This frequently forces a trade-off between API payload and sodium chloride solubility in cold filling suites. At fill-room temperatures below 15°C, sodium chloride can crystallise on the filling needle if the bulk solution is not held in a jacketed tank at 25±2°C. Particulate matter is monitored according to USP <788> Method 1, and extractable volume is checked against USP <1>. Container closure integrity is verified by USP <1207> test methods to reject any vial sealing anomaly caused by silicone tubing compression set. The final product is labelled for subcutaneous administration only; intramuscular injection is avoided in downstream livestock protocols due to the low pH and hypertonic formulation.
Geometric dilution is the first unit operation for a 10% w/w water-soluble powder intended for swine drinking water. Levamisole hydrochloride is added stepwise to a dextrose monohydrate carrier in a 300 L ribbon blender operating at 20 rpm for 30 min. The active is first passed through a 250 µm sieve, and the carrier is pre-dried at 60°C for 4 h to reduce free moisture below 5% w/w. An example dilution calculation is as follows: a batch containing 100 g/kg active is dispensed at 200 g per 1000 L of drinking water, delivering 20 mg/L levamisole hydrochloride. The dry powder is filled into triple-layer aluminium-LDPE sachets at 30% RH because the dextrose carrier becomes tacky above 45% RH and promotes clumping in the automatic sachet jaw. Dosage uniformity of the filled sachets is evaluated by mass uniformity using Ph. Eur. 2.9.5 or an equivalent in-house method. Dissolution is not rate-limiting for soluble powder, but reconstitution time in hard water is measured by adding one sachet to 10 L of water at 20°C under a magnetic stir bar at 200 rpm; the product should fully disperse within 5 min without visible undissolved particles.
The pH of the drinking water matrix is a critical operational boundary for this application. In alkaline borehole water above pH 8.0, the free base form of levamisole can precipitate as a faint white haze, especially when the water is cold and contains carbonate hardness above 300 mg/L as CaCO₃. This is managed on-farm by pre-acidification of the stock solution with citric acid to pH 4.5–5.5 before dosing into the proportional medicator. The farm operator is instructed to avoid simultaneous administration with alkaline chlorinated water because hypochlorite oxidises the imidazothiazole ring and reduces the delivered concentration. The formulation is not recommended for continuous unmonitored use in nipple drinker lines with heavy biofilm because organic residues bind the cationic active substance and reduce recoverable concentration in the water line.
On a dedicated premix line, a 2.5% w/w levamisole hydrochloride premix for incorporation into final feed is produced by stepwise dilution. Equal parts of API and calcium carbonate are blended first in a 500 L double-ribbon mixer for 15 min, then the intermediate mixture is transferred to a second mixer and diluted with ground corn cob to the final 2.5% strength. The carryover threat is not theoretical. Electrostatic adhesion of fine levamisole hydrochloride particles to ungrounded stainless steel surfaces can remove up to 1.5% of the batch from the active phase when relative humidity falls below 20% RH. This is controlled by maintaining the milling and blending room at 45–55% RH and by installing copper grounding straps on the ribbon mixer body. Mixer uniformity is tested by sampling at 10 defined points according to ISO 6497:2002, with an acceptance limit of not more than 5% coefficient of variation for levamisole content. The granulated premix is packaged in multiwall paper bags with a polyethylene liner and a desiccant packet because the calcium carbonate diluent can carry moisture into the product during bulk storage.
Feed mill incorporation uses a secondary dilution of 20 kg premix per tonne of finished feed to achieve a nominal active concentration of 500 mg/kg in the mash. The batch mixer in the feed mill must be flush-audited: after the medicated run, 50 kg of ground corn is passed through the same elevator, mixer, bucket conveyor and pellet die, and the flush is destroyed or diverted. Residue carryover is then verified by assay of the next non-medicated batch using a limit test method. In facilities that pellet the feed, conditioner steam pressure is held at 1.0–1.5 bar and pelleting temperature is kept below 70°C because prolonged high-temperature steam conditioning shortens granule shelf life when the API is sorbed onto a porous carrier. Published data for levamisole hydrochloride recovery after extruded aquaculture feed processing is limited; therefore, aquaculture premix applications require pilot-scale recovery studies before commercial registration.
Extemporaneously compounded levamisole hydrochloride capsules for individual animal treatment are prepared under the veterinary cascade where no licensed tablet strength is available for small ruminants or camelid patients. The compounding record fixes the capsule fill at 120 mg total mass for a 25 mg active capsule using size 3 hard gelatin shells. The diluent is a dry mixture of lactose monohydrate and croscarmellose sodium at a 5% w/w disintegrant level to ensure rapid release when the capsule is administered with a dosing gun. Geometric dilution is performed in a glass mortar with a 50% stepwise increase of the diluent after each trituration pass; total mixing time is at least 12 min to reach acceptable content uniformity under USP <905>. The resulting powder is not compressed, so flowability is managed by conditioning the powder at 35% RH for 24 h before filling into capsules on a hand-operated capsule machine. The final capsules are stored in amber polypropylene vials with a desiccant plug; gelatin shell crosslinking can occur in high-temperature, high-humidity barn storage above 40°C and 75% RH.
Because compounded preparations are batch-prepared under a veterinary prescription, release testing is limited to weight uniformity and organoleptic inspection. A destructive assay is performed on three capsules per batch after extraction with 0.1 N hydrochloric acid and filtration through a 0.45 µm nylon filter. The remaining capsules are labelled with a beyond-use date of not more than 30 days unless a longer stability study is available. This short dating is driven by the absence of a sealed industrial film coating; unpackaged gelatin capsules exchange moisture with the environment and become brittle below 30% RH or tacky above 60% RH. Strongly alkaline diluents such as sodium bicarbonate are avoided because free base precipitation increases content non-uniformity during trituration.
When levamisole hydrochloride is formulated as a 1.5% w/v oral drench for sheep and goats, the critical design factor is not the active concentration but the buffer capacity of the vehicle. A citrate buffer at 0.05 M is prepared from citric acid and sodium citrate to hold the solution at pH 4.6; this prevents the free base from precipitating after the drench enters the alkaline rumen fluid and dilutes. The manufacturing process charges purified water into a 1000 L stainless steel jacketed vessel, then dissolves the citrate buffer, sodium benzoate at 0.2% w/v, propylene glycol at 10% v/v, and finally the levamisole hydrochloride under a low-shear propeller stirrer at 120 rpm. The addition order is fixed because reversing the sequence—adding the API before the buffer—creates a temporary high-pH microzone that produces haze and can reduce potency by 2–3% in scale-up trials. The solution is sparged with nitrogen for 15 min before transfer to a filling line because oxygen uptake in the headspace accelerates sulfite-free browning of the liquid during warehousing.
The drench is packaged in 1 L HDPE bottles with tamper-evident polypropylene caps and a dosing chamber calibrated for the target species. Freeze-thaw testing is part of the release programme; the solution must remain clear after three cycles from -5°C to 25°C, because farm storage in unheated sheds can expose the product to frost. The citrated solvent also protects the active from crystallisation during cold storage. The product line is cleaned with phosphoric acid-based detergents rather than sodium hypochlorite, because hypochlorite residues in the filling circuit degrade the imidazothiazole ring and create a chlorinated oxidation impurity detectable by HPLC at 0.05% area normalisation. The filled drench is sampled according to Ph. Eur. 2.9.35 for delivered volume from the dosing chamber, and the label statement is verified against the actual delivered volume, not the fill volume in the bottle.
Competitive Levamisole 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!
Levamisole hydrochloride, (S)-6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole hydrochloride, CAS 16595-80-5, is supplied as a white to almost white crystalline powder with a molecular mass of 240.75 g/mol. Three physical grades are typically offered under the same chemical monograph: a milled injectable grade for aqueous manufacturing, a direct-compression grade with controlled fines, and a low-dusting premix grade. The grade distinction is based on particle-size distribution, bulk density, bioburden, and endotoxin rather than on chemical assay. The compound is the levorotatory enantiomer of tetramisole; specification of the L-configuration is a release parameter rather than a default identity, because racemic tetramisole exhibits a different host safety and anthelmintic potency profile. Compendial alignment is available through current USP and Ph. Eur. levamisole hydrochloride monographs, with assay, related substances, loss on drying, sulfated ash, residual solvents, and specific optical rotation included in batch release. The API is incorporated into tablets, injectable preparations, capsules, oral powders, granules, medicated premix, and drench or drinking-water solutions. Each application imposes different limits for particle size, bioburden, endotoxin, and processability.
Model differentiation for this API is physical rather than chemical. The milled injectable grade is controlled for low endotoxin, high aqueous dissolution rate, and sub-visible particle load; the direct-compression grade is controlled for sieve retention, bulk density, and flow consistency; the premix grade is controlled for low dusting and carrier adsorption. A batch that fails the injectable-grade endotoxin limit may still be released as a tablet or premix grade only if the endotoxin specification for that route is met and the decision is recorded in the certificate of analysis.
Levamisole acts as a nicotinic acetylcholine receptor agonist at nematode somatic muscle; the L-enantiomer provides the primary anthelmintic effect. The R-enantiomer present in racemic tetramisole is not an inert diluent: it can contribute to off-target receptor effects and requires separate toxicological justification in product dossiers. Enantiomeric control is therefore performed by specific optical rotation in aqueous solution and by chiral HPLC when the API is offered as a substitute for established tetramisole-based formulas. A conventional area-normalisation HPLC assay alone does not detect the R-enantiomer; specific optical rotation according to USP <781> or Ph. Eur. 2.2.7 is therefore run on every batch. The acceptance band is deliberately narrow and negative; deviation toward zero indicates racemisation or contamination with tetramisole. For oral premix, a failed optical rotation test cannot be corrected by blending with compliant material, because chiroptical purity is a safety parameter.
Particle-size distribution for solid dosage grades is normally specified as a sieve retention profile rather than a single d90 value, because levamisole hydrochloride crystals are brittle and can generate fines during pneumatic transfer. For direct-compression tablets, a bimodal distribution with a fraction below 75 µm is often limited to ≤ 35% to prevent feed-frame segregation and die-fill variation on rotary presses. Bulk density and tapped density are measured by USP <616> / Ph. Eur. 2.9.34; flow through an orifice is assessed by USP <1174> / Ph. Eur. 2.9.36. When the fines fraction exceeds the agreed specification, the batch may still be acceptable for wet granulation but not for direct compression. In a high-shear mixer and fluid-bed dryer line, the API is dry-blended with lactose monohydrate, microcrystalline cellulose, and povidone K30 before aqueous granulation; levamisole hydrochloride dissolves partially in granulating fluid and can act as a binder, altering granule hardness and subsequent tablet dissolution. Granule moisture target after fluid-bed drying is commonly 2.0%–3.0%, with endpoint determined by loss on drying at 105 °C rather than by infrared balance only, because residual granulation solvent can interfere with NIR moisture readings.
Batch-to-batch variance in levamisole hydrochloride crystallisation affects downstream performance more than the HPLC assay. Crystallisation from ethanol or aqueous ethanol yields crystals with different aspect ratios; a batch with elongated needles may show higher Carr index and poor flow despite meeting the same sieve specification. Manufacturers of direct-compression tablets therefore compare bulk and tapped density ratios rather than particle size alone. A Hausner ratio above 1.35 typically requires force feeder adjustment or granulation; a ratio below 1.25 is preferred for direct compression. If the API is micronised for oral solutions, the high specific surface area accelerates dissolution but may increase hygroscopic pickup; containers should be resealed under dry nitrogen when RH exceeds 60%.
Release testing for injectable and premix applications combines a common chemical purity platform with route-specific limits. Residual solvents are controlled by headspace gas chromatography against ICH Q3C class limits; levamisole hydrochloride producers using ethanol or methanol in the final crystallisation must report both Class 3 and Class 2 solvents on the certificate of analysis, with methanol restricted to ≤ 3000 ppm and total Class 3 solvents typically justified by Option 2 of ICH Q3C. Elemental impurities are controlled by ICH Q3D; for veterinary injectable products, the parenteral permitted daily exposure for lead is 5 µg/day, for cadmium 2 µg/day, for arsenic 15 µg/day, and for mercury 3 µg/day; these are measured by ICP-MS after closed-vessel microwave digestion according to USP <233> or Ph. Eur. 2.4.20. Bacterial endotoxins are not a default requirement for tablet-grade API, but injectable-grade levamisole hydrochloride must meet a limit derived from the maximum bolus dose and the finished solution limit, commonly an API control of ≤ 0.5 EU/mg when the finished product requires less than 10 EU/mL for a 1 mL/kg dose. Published data for this specific configuration is limited; therefore the exact API endotoxin limit is derived case-by-case using the formula K/M in USP <85>.
| Parameter | Reference method | Acceptance boundary |
|---|---|---|
| Assay (dried basis) | HPLC, USP <621> / Ph. Eur. 2.2.29 | 98.0%–101.0% |
| Specific optical rotation | Polarimetry, USP <781> / Ph. Eur. 2.2.7 | Negative narrow band; L-isomer confirmation |
| Related substances | HPLC area normalisation | Unspecified impurity ≤ 0.10%; total ≤ 0.5% |
| Loss on drying | USP <731> / Ph. Eur. 2.2.32 | ≤ 0.5% |
| Sulfated ash | USP <281> / Ph. Eur. 2.4.14 | ≤ 0.1% |
| Residual solvents | Headspace GC | ICH Q3C Class 2/3 limits |
| Elemental impurities | ICP-MS, USP <233> / Ph. Eur. 2.4.20 | ICH Q3D oral/injectable PDEs |
For compendial release, the HPLC assay is not interchangeable with UV spectrophotometry because related substances can absorb in the same region. The current USP and Ph. Eur. methods use reversed-phase liquid chromatography with UV detection at 215 nm or 220 nm; method transfer between laboratories should include forced-degradation samples to separate the main peak from the principal degradation product. System suitability is run before each sequence; typical acceptance criteria include resolution between levamisole and the closest impurity of NLT 1.5 and tailing factor NMT 2.0. Mobile phase pH must be controlled because the protonation state of the imidazothiazole ring shifts retention time; a pH drift of 0.2 units can shift the main peak by more than 0.5 minutes on a 150 mm × 4.6 mm C18 column.
Premix and granule applications impose a different set of homogeneity constraints. Levamisole hydrochloride is incorporated into veterinary premix formulations at low mass fractions, and the analytical challenge is blend uniformity rather than dissolution. The active is adsorbed onto carriers such as lactose, corncob, or calcium carbonate; electrostatic charging of the API can create dead zones in ribbon blenders if relative humidity is below 30%. Blend uniformity is evaluated by sampling at least 10 locations and assaying for levamisole content with acceptance values of 90.0%–110.0% of label claim and an RSD of ≤ 5.0% for a fully validated mix. When the API is milled to reduce particle size, the resulting fines can increase both hygroscopicity and dust exposure; local exhaust ventilation and dust-tight transfer systems are required because the occupational exposure limit should be established from the safety data sheet and confirmed by industrial hygiene monitoring.
The aqueous solubility of levamisole hydrochloride permits high-concentration injectable solutions without organic co-solvents, but the manufacturing route must remove glass delamination risk, clarify filters, and endotoxin rather than only assay impurities. A formulation batch is typically prepared in Water for Injections, sparged with nitrogen if headspace oxygen exceeds 2 ppm, and adjusted to pH 3.5–4.5 with dilute hydrochloric acid or sodium hydroxide. The solution is passed through a 0.45 µm prefilter and then a 0.22 µm sterilising-grade filter; filter compatibility is confirmed because levamisole hydrochloride at low pH can extract cationic membrane agents from certain nylon membranes, shifting visible particle counts. Final sterilisation may be by moist-heat autoclaving at 121 °C for 15 minutes when the container is a sealed glass ampoule, but the terminal cycle must be validated because levamisole hydrochloride can undergo pH drift under prolonged heating. Sub-visible particulate matter is controlled by light obscuration according to USP <788> Method 1 or Ph. Eur. 2.9.19, with limits of ≤ 6000 particles per container ≥ 10 µm and ≤ 600 particles per container ≥ 25 µm for small-volume parenterals. Insoluble inorganic residues above these limits are often traced to water hardness or stopper interaction rather than the API itself.
Compression of levamisole hydrochloride tablets is more sensitive to moisture than to lubricant concentration. The crystalline powder does not form a stable hydrate under normal warehouse conditions, but surface moisture above 1.0% increases sticking to steel tooling and can produce visually defective tablets on high-speed rotary presses operating above 60 rpm. The API is therefore pre-blended with colloidal silicon dioxide at 0.25%–0.50% w/w and magnesium stearate at 0.50%–1.0% w/w; extended blending beyond 5 minutes after addition of magnesium stearate reduces tablet tensile strength because hydrophobic lubricant films coat the levamisole crystals. Friability is tested according to USP <1216> / Ph. Eur. 2.9.7, with a limit of ≤ 1.0% for uncoated tablets. For capsule filling, a pin-and-disk dosator or tamping machine requires a plug of uniform bulk density; the process is controlled by testing bulk density before encapsulation and by monitoring weight variation at ± 5% of target. Powder blends containing levamisole hydrochloride should not be dried above 60 °C after wet granulation, because higher temperatures can accelerate thermal discoloration and increase the process impurity tracked by HPLC at relative retention time 0.8; if its area exceeds the specification, the batch is rejected because terminal drying cannot remove the degradation product.
In aqueous solution, levamisole hydrochloride is highly soluble, but its stability depends on pH, light, and trace metal ions. Oral drench solutions are commonly buffered to pH 3.0–4.0 because levamisole base precipitates at neutral pH; metallised containers without an internal lacquer are to be avoided because trace copper or iron can catalyse oxidative degradation and form yellow-brown discoloration below the visible threshold. Chelating agents such as disodium edetate are added when raw water hardness exceeds 200 mg/L as CaCO₃; this is an operational boundary rather than a universal requirement. The API should not be combined with strongly alkaline feed matrices or mineral premixes containing free calcium oxide, because local pH at the particle surface can convert the hydrochloride salt to the poorly soluble free base and reduce oral bioavailability. For drinking-water medication, the stock solution is protected from sunlight, and exposure to UV is limited because the thioether-imidazole ring system can undergo photolytic cleavage. Published data for this specific configuration is limited; therefore photostability studies per ICH Q1B are required for any clear multidose plastic container.
Compared with macrocyclic lactone APIs such as ivermectin, levamisole has a narrower therapeutic margin and a different resistance mechanism; it is used in rotation or combination where nematode populations show reduced susceptibility to benzimidazoles. This pharmacological difference does not relax the requirement for residue withdrawal periods under regional marketing authorisations. For solid dosage forms, levamisole hydrochloride is often blended with oxyclozanide or praziquantel in multi-active anthelmintic premixes; in such formulations, compatibility is assessed by binary forced-degradation samples rather than by compendial API release alone, because the secondary amine of levamisole can form adducts with reducing excipients such as lactose under accelerated storage conditions.
