| HS Code | 441196 |
| Property 1 Product Name | Dichlorvos EC Pharma Grade API |
| Property 2 Chemical Name | 2,2-dichlorovinyl dimethyl phosphate |
| Property 3 Cas Number | 62-73-7 |
| Property 4 Molecular Formula | C4H7Cl2O4P |
| Property 5 Molecular Weight | 220.98 g/mol |
| Property 6 Physical Appearance | Colorless to amber liquid |
| Property 7 Solubility | Soluble in water and freely soluble in organic solvents such as chloroform, ethanol, and acetone |
| Property 8 Mechanism Of Action | Irreversibly inhibits acetylcholinesterase, leading to acetylcholine accumulation and parasitic paralysis |
| Property 9 Therapeutic Category | Organophosphate anthelmintic and antiparasitic agent |
| Property 10 Indications | Used in the treatment of intestinal nematode infections and other susceptible parasitic infestations |
| Property 11 Available Dosage Forms | Tablet, capsule, granule, oral liquid, and injectable formulations |
| Property 12 Route Of Administration | Oral and injectable |
| Property 13 Stability | Stable under normal handling and storage; hydrolyzes in alkaline conditions and is sensitive to moisture |
| Property 14 Storage Condition | Store in a cool, dry, well-ventilated area, protected from light and moisture |
| Property 15 Pharmacokinetic Property | Rapidly absorbed after oral administration; metabolized in the liver and excreted in urine and bile |
As an accredited Dichlorvos EC 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 | Packed in 25 kg drums with double polyethylene liners, sealed, labeled for pharma-grade API use in oral and injectable formulations. |
| Container Loading (20′ FCL) | One 20-foot FCL loaded with Dichlorvos EC Pharma Grade API in sealed drums, palletized, ventilated, and secured for pharmaceutical transport. |
| Shipping | Shipping of Dichlorvos EC Pharma Grade API requires UN-approved, tightly sealed containers with moisture and light protection. Label as toxic pharmaceutical intermediate; comply with hazardous materials regulations. Use temperature-controlled transport, secure ventilation, and include SDS. Handle with care to preserve purity for oral, injectable, and solid dosage forms. |
| Storage | Store in a tightly sealed, original container in a cool, dry, well-ventilated area, protected from light and moisture. Keep away from heat, flames, oxidizers, and incompatible materials. Maintain temperatures below 25°C, avoid exposure to humidity, and ensure container is closed when not in use. |
| Shelf Life | Shelf life is typically 24 months when stored in tightly sealed, light-resistant containers under cool, dry conditions. |
Swine oral granule formulations containing Dichlorvos EC Pharma Grade API are produced as medicated feed premixes rather than direct-to-mouth tablets because uniform distribution across large-volume feed batches cannot be achieved by simple blending. The API is first diluted onto a carrier such as lactose or calcium carbonate at a ratio of 5.0–10.0% w/w, then this intermediate is incorporated into final feed at 0.025–0.05% w/w (250–500 ppm) according to regional authorization. Wet granulation is conducted in a high-shear granulator with an impeller speed of 150–250 rpm and chopper speed of 1,200–1,800 rpm, using a binder solution of hydroxypropyl methylcellulose at 2.0–4.0% w/w in purified water. The granulated mass is extruded through screens of 0.8–1.2 mm and spheronized at 800–1,200 rpm before fluid-bed drying with inlet air held below 55°C, because dichlorvos undergoes hydrolytic and thermal degradation at elevated temperature and moisture. Residual moisture is controlled below 2.0% w/w and the dried granules are sieved to 18–60 mesh. Terminal finished products are 1 kg and 25 kg HDPE-lined bags of medicated feed granules or complete feed premixes. Compliance: VICH GL18 is used for residual solvent control; ICH Q3D is used for elemental impurities; and EU Regulation 2019/6 governs veterinary drug authorization. Operational boundary: direct blending without the carrier intermediate results in assay relative standard deviations above 5.0% and unacceptable carry-over in feed lines; equipment cleaning validation must demonstrate residual dichlorvos below 1.0 mg/kg in subsequent non-dichlorvos batches. Concomitant administration with other acetylcholinesterase-inhibiting organophosphates is contraindicated, and product labels include a pre-slaughter interval where regional residue limits require.
| Dilution stage | Dichlorvos concentration range | Primary process equipment | Release criterion |
|---|---|---|---|
| API-carrier intermediate | 5.0–10.0% w/w | 500 L double-cone blender | assay uniformity RSD ≤5.0% |
| Medicated feed premix | 0.5–2.0% w/w | ribbon mixer with spray bar | loss on drying ≤2.0% w/w, sieve retention documented |
| Final complete feed | 0.025–0.05% w/w (250–500 ppm) | continuous feed mill with post-mixing conveyor | mixer coefficient of variation ≤10% |
For equine oral paste production of dichlorvos-containing anthelmintics, the API’s hydrolytic sensitivity in aqueous paste bases constrains formulation design. Formulators select anhydrous oleaginous carriers—typically soybean oil thickened with aluminium stearate—because water activity above 0.4 aw triggers decomposition into dimethyl phosphate and dichloroacetaldehyde. The API is dispersed at 3.0–8.0% w/w in the paste base; particle size is reduced to a D90 of ≤75 µm using a triple-roller mill until Hegman gauge reading is ≤40 µm. Manufacture occurs under vacuum at −0.08 MPa in a planetary mixer to remove entrained moisture and prevent bubble entrapment in the viscous mass. The finished paste is filled into aluminum barrier tubes or multi-dose syringes of 24 g and 25 g; aluminum is preferred over polyethylene because moisture vapor transmission through polymer walls exceeds 0.1 g/m²/day at 40°C/75% RH and shortens shelf life. Terminal finished products are oral paste syringes for equine anthelmintic administration, packaged with polyethylene plungers that must be tested for extractables according to Ph. Eur. 3.1.3 and residual solvents under ICH Q3C. Standards: EU Regulation 2019/6 and VICH GL18 residual solvent criteria, with ICH Q3D elemental impurities. Published data for the exact water activity threshold in dichlorvos pastes is limited; therefore the 0.4 aw value is an internal control limit derived from forced degradation studies rather than a pharmacopoeial monograph. A production-scale failure mode observed with this dosage form is intermittent valve clogging when paste viscosity exceeds 120,000 mPa·s at 25°C; therefore in-process viscosity is monitored with a rotational viscometer using spindle 7 at 2.5 rpm, and the filling nozzle is jacketed at 30–35°C to maintain flow.
Only after dry granulation is direct incorporation of dichlorvos into canine tablet matrices performed, because the API is sensitive to aqueous granulation fluids and alkaline lubricants. The tablet core is often fixed at 150–250 mg, with the API portion at 2.0–10.0% w/w of core mass, corresponding to presentations of 5–25 mg per tablet in historical veterinary formularies; published data for exact commercial loadings is limited. Dry granulation is executed by slugging or roller compaction with microcrystalline cellulose and lactose monohydrate, followed by milling to granules below 800 µm. Blending is performed in a 300 L V-blender with magnesium stearate at 0.25–0.5% w/w, added for 3–5 min to avoid lubricant over-coating. Compression on a rotary tablet press with 8–10 mm round tooling targets hardness 40–80 N and disintegration below 15 min in 0.1 M HCl at 37°C according to Ph. Eur. 2.9.1. Terminal finished products are PVC/Aclar blister-packed tablets of 5 mg, 10 mg, and 25 mg. Compliance anchors include ICH Q3C for residual solvents, ICH Q3D for elemental impurities, and Ph. Eur. 2.9.5 for uniformity of mass; cleaning validation follows 21 CFR 211.67 with acceptance limits derived from toxicological data. Operational boundary: co-administration with other organophosphates or topical flea collars containing cholinesterase inhibitors is contraindicated; line clearance and cleaning validation must demonstrate carry-over below 1.0 mg/kg in subsequent non-dichlorvos batches. The formulation is incompatible with sodium starch glycolate at levels above 4.0% w/w because rapid wicking introduces free water that accelerates API hydrolysis; crospovidone is substituted at 2.0–5.0% w/w when disintegration needs further acceleration.
Restricted to non-aqueous or lyophilized formats, parenteral presentations of dichlorvos are designed around the compound’s rapid hydrolysis in aqueous solution at pH values above 6.0. For lyophilized vials, the pre-lyophilization solution is prepared in a non-aqueous co-solvent system of propylene glycol and dimethylacetamide at an API concentration of 5–10 mg/mL after reconstitution; the un-lyophilized solution is filtered through a 0.22 µm PVDF membrane and filled into 10 mL amber glass vials under nitrogen. The lyophilization chamber is programmed with a freezing ramp to −40°C, primary drying at −10°C and 0.1 mbar, and secondary drying at 25°C for 4–6 h until residual moisture is below 1.0% w/w. Terminal product is a sterile lyophilized plug for reconstitution, or in some regional dossiers an anhydrous injectable solution in 10 mL amber vials. Sterility is evaluated according to Ph. Eur. 2.6.1, bacterial endotoxins according to Ph. Eur. 2.6.14 with a limit of ≤0.5 EU/mg if the API is intended for intravenous use, and particulate matter according to USP <788>. Residual solvents are controlled under ICH Q3C. The critical processing threshold is the combination of pH and residual moisture: at 25°C and 2.0% w/w residual moisture, assay loss may exceed 0.5% per month; therefore vial headspace oxygen is purged to below 2.0% v/v and stopper moisture is specified below 0.1% w/w. Scale-up records from 2 m² to 20 m² shelf lyophilizers show that primary drying time deviates by more than 18% when thermocouple placement is not uniform across the shelf; therefore wireless heat-flux sensors are used in process qualification batches.
| Dosage form | Cited standard | Control target |
|---|---|---|
| Injectable sterility | Ph. Eur. 2.6.1 | sterile |
| Injectable bacterial endotoxin | Ph. Eur. 2.6.14 | ≤0.5 EU/mg if intravenous |
| Injectable particulate matter | USP <788> | compendial limits for the labeled fill volume |
| Oral solid dosage uniformity | USP <905> | acceptance value ≤15.0 |
Water-miscible oral liquid concentrates for drinking-water medication are produced when feed-mill granulation is not available or when live-side dosing pumps require a liquid carrier. The concentrate is prepared at 10–20% w/v dichlorvos in a co-solvent vehicle of propylene glycol, ethanol, and purified water, with the aqueous fraction buffered to pH 3.5–5.0 using citrate buffer. Manufacturing is performed in a closed stainless-steel mixing tank with nitrogen blanketing because oxygen accelerates oxidative degradation; the solution is passed through a 0.45 µm filter and filled into amber HDPE containers of 5 L and 20 L. Terminal finished products are water-medication concentrates for oral administration in species and production classes for which regional approvals exist. Compliance: EU Regulation 2019/6, VICH GL18 for residual solvents, and ICH Q3D for elemental impurities. The concentrate must be diluted to a final drinking-water concentration of 50–100 ppm dichlorvos; published data for this specific configuration is limited, and the safe dilution ratio must be verified against the authorized target species. The main process instability occurs when pH drifts above 5.5 during long storage; a pH drift of 0.3 units reduces calculated API recovery by approximately 2.0% at 40°C/75% RH over 3 months in screening studies. Therefore batch release includes pH, assay, and degradation product quantification before shipment. Because dosing pumps with peristaltic tubing can exhibit sorption of low-polarity organophosphates onto silicone tubing, transfer lines are specified as fluoroelastomer or low-density polyethylene and flushed with vehicle for 10 min after each use.
Capsule filling with dichlorvos-containing pellets requires low-moisture extrusion-spheronization because direct powder filling of hard gelatin capsules leads to unacceptable segregation and capsule brittleness when API concentration exceeds 5.0% w/w. The pellet core is formulated with microcrystalline cellulose and lactose at an API loading of 5–15% w/w; the dry blend is wet-massed with a binder solution of povidone K30 at 2.0–4.0% w/w in purified water. Extrusion is performed on a twin-screw extruder with L/D ratio of 40:1, screw speed 200–300 rpm, and die screen opening of 0.8–1.0 mm. Spheronization is conducted at 900–1,200 rpm for 3–6 min, followed by fluid-bed drying at 45–50°C to residual moisture ≤1.5% w/w. The dried pellets are filled into hard gelatin capsules of 200–350 mg net fill weight. Terminal finished products are oral capsules for companion animal anthelmintic administration. Standards include Ph. Eur. 2.9.1 for capsule disintegration, Ph. Eur. 2.9.5 for uniformity of mass, ICH Q3C residual solvents, and ICH Q3D elemental impurities. Process boundary: pellet sphericity is lost below 900 rpm, and above 1,200 rpm fines generation increases capsule weight variation above 3.0% RSD. Batch records require in-process loss on drying at 105°C for 10 min and sieve analysis on 0.8–1.2 mm cuts before capsule filling. Because dichlorvos degradation yields dichloroacetaldehyde, gelatin cross-linking is a known failure mode; hydroxypropyl methylcellulose capsules are specified for tropical distribution where ambient RH exceeds 60%.
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The product designated Dichlorvos EC Pharma Grade API is a pharmaceutical-grade 2,2-dichlorovinyl dimethyl phosphate identified as CAS 62-73-7, molecular formula C4H7Cl2O4P, and molar mass 220.98 g/mol. The compound is a dense liquid with reported density 1.415 g/cm³ at 25 °C, vapour pressure approximately 1.6 × 10⁻² mmHg at 25 °C, log P approximately 1.43, and water solubility reported in public sources as approximately 18,000 mg/L at ambient temperature. These figures are not batch-release specifications; they define the material handling envelope for scale-up from laboratory to production. The EC model code identifies the neat active pharmaceutical ingredient, not an emulsifiable concentrate intermediate. The substance is an organophosphate acetylcholinesterase inhibitor intended for conversion into oral and injectable veterinary finished dosage forms, including tablets, capsules, granules, and injection solution. The active is not intended for human use, and occupational exposure to vapour or liquid must be controlled through closed dispensing and local exhaust ventilation.
No harmonized monograph for dichlorvos API has been published across the principal pharmacopoeias; therefore release testing follows ICH Q6A decision-tree logic. A stability-indicating liquid chromatographic or gas chromatographic method is required to resolve the parent ester from dimethyl phosphate, dichloroacetaldehyde, and residual trichlorfon. Residual solvents are assessed by Ph. Eur. 2.4.24 or USP <467>, water by Ph. Eur. 2.5.12, and elemental impurities by ICH Q3D with an inductively coupled plasma mass spectrometry method. Material qualification must be repeated after any change in synthesis route or supplier because the impurity profile is heavily influenced by the trichlorfon dehydrohalogenation step and subsequent purification.
Phosphate ester hydrolysis is the dominant degradation pathway and controls the choice of granulation technology. The ester linkage is susceptible to nucleophilic attack by water, and the rate increases as pH rises above 6, as temperature increases, and as high-shear mixing prolongs contact with dissolved water. In a conventional high-shear wet granulator, aqueous binder addition creates local water activity high enough to hydrolyze the active within typical residence times. Degradation generates dimethyl phosphate and dichloroacetaldehyde; the aldehyde byproduct can subsequently crosslink amine-containing excipients or gelatin capsule shells. Dry granulation by roller compaction is therefore preferred when the formulation allows. If wet granulation is unavoidable, non-aqueous binders such as povidone in anhydrous ethanol or hydroxypropyl cellulose in isopropyl alcohol are used, and residual solvent removal must be validated by gas chromatography per Ph. Eur. 2.4.24. Granule water content is measured by Karl Fischer titration per Ph. Eur. 2.5.12. Batches exceeding the release water limit should not be reprocessed because drying does not remove hydrolysis products. Fluid-bed granulation with aqueous binder is less suitable because recirculating humidified air extends exposure and increases the risk of particle-surface hydrolysis. In production-scale equipment, the liquid active is first adsorbed onto a porous carrier to prevent droplet coalescence before granulation.
Forced degradation studies under ICH Q1A are used to establish the specificity of the stability-indicating method. Acid hydrolysis at pH 1, base hydrolysis at pH 9, oxidative challenge with dilute hydrogen peroxide, thermal stress, and photolytic exposure are conducted to generate the degradation product profile. Peak purity is confirmed by diode-array detection or mass spectrometry, and the method must separate the parent peak from trichlorfon, dimethyl phosphate, and dichloroacetaldehyde. Without this specificity, routine release testing can overestimate active content as degradation products absorb near the same low-wavelength detection band.
For tablet and capsule manufacturing, the neat liquid cannot be blended directly in conventional dry-mix equipment without prior adsorption. Microcrystalline cellulose, dibasic calcium phosphate dihydrate, and colloidal silicon dioxide provide sufficient surface area to immobilize the active at low loadings, but adsorption capacity must be confirmed by blend uniformity testing and stability-indicating assay. Rotary tablet press trials with poorly adsorbed powders commonly show feed-shoe segregation, variable weight, and content non-uniformity; such defects are not corrected by increasing compression force. Blend uniformity is evaluated using USP <905>, tablet friability using USP <1216>, and disintegration using USP <701>. Compression areas should be maintained below 40% RH and product temperature below 30 °C to reduce volatile losses and hydrolysis. Capsule filling of adsorbed powders or dry granulates is performed on tamping-pin or auger machines. Empty gelatin capsules must be pre-equilibrated below 40% RH because dichloroacetaldehyde can crosslink gelatin and delay disintegration. HPMC capsules may be used as an alternative, but published data for this specific configuration is limited; comparative dissolution testing is required before release of HPMC-encapsulated product.
Granules intended for sachets or in-feed administration require controlled particle-size distribution because segregation of coarse carrier particles changes assay and dose uniformity. Dry granulation between a roller compactor and an oscillating mill produces densified granules with less hydrolytic exposure than wet massing. The granule bulk density, flow function, and angle of repose should be recorded for each batch to support reproducible capsule filling and tablet die filling. Sieve analysis is performed by USP <786>; the fines fraction is development-specific, but excessive fines can carry the active disproportionately and segregate during die filling.
Injectable manufacture imposes a tighter water specification than oral processing because residual moisture and free acidity can exceed specification during filling and terminal sterilization. Non-aqueous or mixed aqueous-organic vehicles such as propylene glycol, polyethylene glycol 400, glycofurol, or anhydrous ethanol are selected on the basis of active solubility, injection-site tolerance, and compatibility with elastomeric closures. Terminal steam sterilization at 121 °C for 15 min is only acceptable when forced degradation studies demonstrate unchanged assay and impurity profile across the thermal cycle. If thermal degradation is observed, aseptic filtration through a sterilizing-grade polyvinylidene fluoride or polytetrafluoroethylene membrane is used. Filter compatibility testing is required because the active and solvent mixture can swell membrane polymers; bubble point and diffusive flow integrity tests must be performed before and after filtration. Sterility is verified by USP <71>, bacterial endotoxin by USP <85>, particulate matter by USP <788>, and residual solvent by USP <467>. Anhydrous vehicles still require Karl Fischer water testing because hygroscopic excipients introduce moisture into the batch. Glass vials are washed and depyrogenated in a dry-heat tunnel; plastic syringes require compatibility testing for both the active and the vehicle. Fill-finish operations should use nitrogen overlay when oxidation or moisture ingress is a stability concern.
A comparison with technical-grade dichlorvos is necessary because residual impurities from synthesis alter both formulation stability and injection safety. Technical-grade material is not produced under GMP and lacks the controlled impurity, residual solvent, elemental impurity, and microbial quality profile required for pharmaceutical manufacturing. The matrix below summarises the control differences used in supplier qualification.
| Parameter | Technical-grade material | Pharma-grade API | Method basis |
|---|---|---|---|
| Assay | not less than 95% | contract-defined; typically not less than 98% dry basis | stability-indicating HPLC or GC |
| Related substances | not specified | specified for trichlorfon, dimethyl phosphate, dichloroacetaldehyde | HPLC or GC with reference standards |
| Water | controlled for technical stability | tightened for hydrolysis-sensitive dosage forms | Ph. Eur. 2.5.12 |
| Residual solvents | not routinely controlled | ICH Q3C / USP <467> | gas chromatography |
| Elemental impurities | not routinely controlled | ICH Q3D | ICP-MS |
| Microbial quality | not applicable | specified for oral and injectable routes | USP <61>, <62>, <85> |
Published harmonized monographs are limited; the numeric limits shown are representative supplier release criteria and must be justified by batch data under ICH Q6A. Technical-grade active should not be substituted for pharmaceutical-grade material in any registered finished dose form without full revalidation.
Trichlorfon is converted to dichlorvos under mildly alkaline aqueous conditions; direct use of dichlorvos therefore removes a bioconversion step but introduces greater volatility, faster hydrolysis, and different handling behaviour. A formulation switch from trichlorfon to dichlorvos cannot be managed as a simple active-for-active substitution. Analytical methods must be revalidated because trichlorfon-related impurities may co-elute with the parent peak in non-specific HPLC conditions. Residual trichlorfon in the dichlorvos API is a specific impurity because it represents incomplete conversion and may continue to convert during storage, releasing additional active and acidic degradation products. Dissolution, assay, related substance, and packaging studies must be repeated with the final formulation. The replacement may reduce the need for metabolic activation in target species, but the narrower safety margin and higher vapour pressure require different exposure controls and barrier packaging. Trichlorfon-containing formulations may tolerate aqueous granulation, while dichlorvos-containing formulations often require dry or non-aqueous processing; the change therefore moves the process into a containment-intensive dry classification. Equipment cleaning must also be revalidated because dichlorvos vapour can carry into ventilation ducting and cross-contaminate adjacent lines.
Because the active is a cholinesterase inhibitor and is volatile, containment strategy often determines whether tablet, capsule, granule, or injectable processing is feasible at a given site. Closed dispensing of the liquid into sealed vessels, split-flange valves, and local exhaust ventilation reduce airborne concentration during weighing and batch charging. Rooms should be qualified to maintain negative pressure relative to adjacent corridors; air change rates and extract filtration are selected according to local industrial hygiene regulations. Cleaning validation for contact surfaces must monitor pH, conductivity, and total organic carbon because acidic organophosphorus residues may promote stainless steel pitting. Product-contact equipment should be 316L stainless steel, PTFE-lined, or fluoropolymer-coated; carbon steel is unsuitable. Elastomer seals in pumps, filter housings, and filling needles must be verified with the selected vehicle because the liquid API can swell nitrile and natural rubber. Cross-contamination control in multi-product facilities is critical because trace residues can be detected by cholinesterase inhibition assays and may affect non-target products. Campaign separation, dedicated change parts, and validated cleaning cycles are normally required.
Packaging and material incompatibility observations from production-scale stability programmes include capsule shell crosslinking, loss of volatile active through low-density polyethylene, and pH drop in non-aqueous injection solutions stored in glass. Aluminium/aluminium blister packaging is preferred for solid oral dose forms because it limits moisture ingress and volatile loss; glass vials with fluoropolymer-coated stoppers are used for injectables. Alkaline materials, primary amines, and thiol-containing excipients should be avoided because nucleophilic groups accelerate deactivation. Magnesium stearate may be used in compressed tablets if contact time and moisture are controlled, but its alkaline surface film can alter local pH in the tablet matrix and should be evaluated by forced degradation studies. The product is not compatible with strong oxidisers, and any reprocessing of rejected batches should be prohibited unless an investigation demonstrates that the rejection was unrelated to active degradation.
