| HS Code | 134070 |
| Chemical Name | Ethylene Diamine |
| Cas Registry Number | 107-15-3 |
| Molecular Formula | C2H8N2 |
| Molecular Weight | 60.10 g/mol |
| Grade | Veterinary Grade API |
| Appearance | Clear, colorless to slightly yellow liquid with characteristic ammonia-like odor |
| Solubility | Miscible with water; soluble in ethanol; slightly soluble in ether |
| Specific Gravity | 0.899 at 20°C |
| Melting Point | 8°C |
| Boiling Point | 118°C |
| Ph 1 W V Aqueous Solution | Approximately 11.3 |
| Assay Purity | Minimum 99.0% w/w on anhydrous basis |
| Storage Conditions | Keep in tightly closed, light-protected containers in a cool, dry, well-ventilated area; avoid contact with moisture, air, acids, and oxidizing agents |
| Compatible Dosage Forms | Tablets, Injections, Capsules, Powders, Granules, Premix, and Solutions |
As an accredited Ethylene Diamine 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 | Available in 25 kg sealed drums with moisture-proof lining, ensuring safe handling and stability of veterinary-grade Ethylene Diamine API. |
| Container Loading (20′ FCL) | 20′ FCL: Ethylene Diamine Veterinary Grade API packed in sealed drums, palletized, securely braced, with proper ventilation and containment. |
| Shipping | Shipping of Ethylene Diamine Veterinary Grade API requires compliance with hazardous material regulations. Pack in sealed, moisture-proof containers with clear labeling. Ensure temperature-controlled transport to prevent degradation. Include Material Safety Data Sheets and documentation for customs. Protected from light and extreme conditions to maintain purity and stability for subsequent pharmaceutical manufacturing. |
| Storage | Store in a cool, dry, well-ventilated area at controlled room temperature, ideally 15–25°C. Keep tightly sealed in original, light-resistant containers, protected from moisture, heat, and direct sunlight. Avoid contact with acids, oxidizers, and metals. Ensure proper labeling and segregation to prevent cross-contamination. Maintain good manufacturing hygiene throughout shelf life. |
| Shelf Life | Shelf life is 24 months from manufacture date when stored unopened in a cool, dry place, protected from light and moisture. |
In aqueous parenteral aminophylline manufacturing, veterinary-grade ethylene diamine functions as the solubilizing counterion for theophylline, not as an inert diluent. Theophylline solubility in water at 25°C is approximately 8.3 mg/mL; formation of the theophylline–ethylene diamine complex displaces the equilibrium enough to make 25 mg/mL solutions feasible without ethanol, propylene glycol, or other co-solvents. Bulk aminophylline used for injection is controlled under the USP Aminophylline monograph, which sets ethylenediamine content at 13.5–15.0% on the anhydrous basis, corresponding to the stoichiometric 2:1 theophylline-to-ethylene diamine complex and a theoretical ethylenediamine content of 14.3%. During compounding, water for injection is sparged with nitrogen to dissolved oxygen below 0.5 mg/L, aminophylline is dissolved at 30–35°C, and the pH is adjusted to 8.2–9.0 with additional ethylene diamine or dilute hydrochloric acid. pH values above 9.0 accelerate theophylline degradation and increase venous irritation upon administration; pH values below 8.0 risk theophylline precipitation as the ethylenediamine ionizes and the free acid form partitions out of solution. The solution is passed through a 0.22 µm PVDF cartridge filter and filled into amber Type I glass vials under nitrogen overlay; if terminal moist-heat sterilization is selected, cycle validation at 121°C for 15 min is typical. Finished presentations include 25 mg/mL aminophylline injection in 10 mL, 20 mL, and 50 mL single-dose vials, used by intravenous administration in equine, canine, and feline patients. Compendial release testing includes pH by USP <791>, bacterial endotoxins by USP <85>, and particulate matter by USP <788>. Equipment surfaces should avoid aluminium or copper alloys because primary amines and alkaline filtrates can strip metal ions into the solution and form visible precipitation on accelerated storage.
For oral solid dosage forms, ethylenediamine is not a neutral filler; its concentration governs local surface pH during disintegration and dissolution. A 100 mg aminophylline tablet contains approximately 84.0–87.4 mg theophylline and 13.5–15.0 mg ethylenediamine, and the counterion release rate directly affects the wetting of hydrophobic theophylline particles in gastric fluid. Tablet formulations for veterinary use typically begin with wet granulation of aminophylline and microcrystalline cellulose (PH-102) using isopropyl alcohol as the granulation liquid; water-free processing prevents premature hydration of the ethylenediamine salt and avoids the sticky dihydrate transition. Drying in a fluid-bed dryer at 45°C to a moisture endpoint below 2.0% w/w is required to prevent ethylenediamine migration to the tablet surface, which otherwise causes mottling and increases friability. Granules are lubricated with magnesium stearate at 0.5% w/w and compressed on a 16-station rotary tablet press at 8–14 kN; target hardness is 5–9 kp and friability is maintained below 1.0%. Over-lubrication above 1.0% w/w magnesium stearate delays disintegration beyond 15 min and reduces dissolution in 0.1 N HCl because the hydrophobic lubricant film blocks ethylenediamine release. Dissolution testing under USP <711> with paddle speed 50 rpm in 900 mL of pH 1.2 simulated gastric fluid is used to verify release; failure commonly traces to granule overwetting or excess fine particles generated during milling. Ethylene diamine-bearing formulations should avoid lactose monohydrate if direct compression is attempted because the primary amine can react with reducing sugars and produce brown discoloration during storage. Finished oral solids include 50 mg, 100 mg, and 200 mg film-coated veterinary tablets, as well as compounded capsules in gelatin or HPMC shells for dose titration in small animals.
| Application | Standard or monograph | Critical numeric requirement | Test method |
|---|---|---|---|
| Aminophylline bulk | USP Aminophylline | Ethylenediamine 13.5–15.0%; theophylline 84.0–87.4% | Gas chromatography; liquid chromatography |
| Aminophylline injection | USP Aminophylline Injection | pH 8.2–9.0; particulate matter USP <788> | pH USP <791>; light obscuration |
| Ethylenediamine dihydroiodide feed powder | 21 CFR 573.420 | Iodine equivalent 80.3% theoretical; assay ≥98.0% | Redox titration; argentometric titration |
| EDDI mineral premix | AAFCO Official Publication | Iodine homogeneity CV ≤5.0% in finished blend | ICP-MS after alkaline digestion |
Ethylene diamine-derived ethylenediamine dihydroiodide, commonly abbreviated EDDI, is one of the permitted iodine sources for livestock feeds. The synthesis consumes 1 mol ethylene diamine (60.10 g/mol) and 2 mol hydriodic acid; the resulting salt has molecular mass 315.92 g/mol and a theoretical iodine content of 80.3%. In production, hydriodic acid (57% w/w technical grade) is fed into a glass-lined reactor containing veterinary-grade ethylene diamine under jacket cooling at 10–20°C, because the neutralization is strongly exothermic and high local adiabatic rise can volatilize iodine. Vacuum evaporation at no more than 60°C crystallizes the salt; the crystals are washed with acetone, dried at 50°C to a moisture specification below 0.5% w/w, and milled through 60–80 mesh. The feed-additive listing under 21 CFR 573.420 and the AAFCO Official Publication requires an EDDI assay of 98.0% or higher on the anhydrous basis. For premix manufacture, crystalline EDDI is adsorbed onto calcium carbonate or silica carriers; a typical micro-premix is targeted to 1.0% w/w iodine, and inclusion of 0.5–2.0 kg of this premix per tonne of complete feed yields 5–20 mg iodine per kg, depending on species-specific formulation limits. Finished product types include pure EDDI crystalline powder, spray-dried granular EDDI, mineral premixes, free-choice salt mixes, and lick-block concentrates. Because EDDI is water-soluble and oxidizes under prolonged exposure to light and metal ions, lined storage and nitrogen-purged packaging are standard.
Compounded and registered aminophylline oral solutions for companion animals use the same ethylenediamine–theophylline complex but require different pH control than parenteral products. In a typical aqueous oral solution, aminophylline is dissolved in purified water warmed to 35°C; the ethylenediamine component is present at 13.5–15.0% of the aminophylline mass, so a 500 mg aminophylline load contributes 67.5–75 mg ethylenediamine. The pH is adjusted with dilute hydrochloric acid or additional ethylene diamine to a target of 8.2–8.8, high enough to maintain theophylline in its ionized, soluble state but low enough to avoid excessive bitter taste and mucosal irritation during oral administration. Nitrogen purging is performed before the solution is filtered through a 0.45 µm polyethersulfone membrane and filled into amber PET bottles or unit-dose syringes. Compounded oral solutions prepared under USP <795> follow default beyond-use dating of 14 days at 2–8°C unless a preservative system is validated. Freezing must be avoided because the temperature dependence of ethylenediamine ionisation reduces the equilibrium solubility of theophylline and can produce crystal growth on thawing; storage at 2–8°C is standard. Terminal product forms include a 105 mg/5 mL oral solution and compounded feline oral syringes in the 10–25 mg/mL range. Appearance testing is performed at release and after accelerated storage at 40°C/75% RH for 4 weeks; crystal-free clarity is the primary physical stability criterion.
The limiting process variable in EDDI premix use is not iodine content but spatial homogeneity in the final total mixed ration. EDDI crystals are fine, with typical D50 between 75 µm and 150 µm; they adhere to ground limestone carriers (40–80 mesh) only when a binder such as vegetable oil is applied at 0.5–1.0% w/w in a ribbon mixer. Without binder, air entrainment and vibratory settling during pneumatic conveying can segregate EDDI from the mineral fraction, producing iodine coefficient of variation values above 10% in grab samples. The preferred sequence is to pre-blend EDDI with 10 kg calcium carbonate per 1 kg EDDI in a V-blender for 10 min, then discharge this pre-mix into the main ribbon mixer for a further 8–10 min; the finished mineral pack should have an iodine assay CV below 5.0%. Premix addition is typically 0.5–2.0 kg per tonne of complete feed for a 1.0% iodine premix, yielding 5–20 mg/kg iodine in the final ration. Terminal products include pelleted concentrates, coarse granules, free-choice mineral blocks, and TMR delivery systems in dairy and beef operations. Feed hygiene compliance follows EU 183/2005 or regional equivalents; iodine assay in finished feed is performed by ICP-MS after alkaline digestion.
Synthesis of calcium disodium edetate injection from ethylene diamine feedstocks illustrates a downstream application in which the veterinary-grade material is consumed as an upstream intermediate rather than as a formulation excipient. The Mannich condensation uses 1.0 mol ethylene diamine, 4.0 mol sodium cyanide, and 4.0 mol formaldehyde under alkaline conditions to form tetrasodium EDTA; after acidification and chelation with calcium carbonate, the product is crystallized as calcium disodium edetate. The injectable product is typically formulated at 200 mg/mL calcium disodium edetate in water for injection, adjusted to pH 6.5–8.0, filtered through 0.22 µm sterilizing filters, and terminally sterilized at 121°C for 15 min. Compendial control follows USP Calcium Disodium Edetate Injection; bacterial endotoxin testing under USP <85> and particulate matter testing under USP <788> apply. The key process limit is residual free ethylene diamine; it is monitored by derivatization HPLC, and published data for a universal residual limit in veterinary formulations is limited because specifications are set by individual marketing authorizations. Finished products are used in companion-animal heavy-metal toxicosis protocols when regional veterinary drug legislation permits the use of human-registered chelation products under prescription. This application does not use ethylene diamine as a direct tablet or premix additive; the ethylene diamine feedstock purity determines the impurity profile of the final injectable chelating agent.
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Ethylene Diamine Veterinary Grade API (CAS 107-15-3; empirical formula C₂H₈N₂; relative molecular mass 60.10 g/mol) is released as a clear, colourless to pale-yellow hygroscopic liquid with an ammoniacal odour. The material is intended for use as a formulation intermediate, pH regulator, stabiliser, and counter-ion donor in veterinary dosage forms encompassing tablets, injectable solutions, capsules, powders, granules, premixes, and oral solutions. Standard supply configurations include EDA-VET-0500 (0.5 kg amber glass bottle, nitrogen-purged), EDA-VET-0250 (25 kg high-density polyethylene drum), EDA-VET-1000 (100 kg 316L stainless steel drum), and EDA-VET-BULK (1000 kg composite intermediate bulk container with nitrogen overlay). Release is performed under a veterinary API control strategy aligned with 21 CFR 211 and ICH Q7; batch documentation includes certificate of analysis, safety data sheet, and retained sample traceability. The material is not a lower-purity industrial amine, and the following sections define the specification set, processing constraints, and points of divergence from technical and alternative amine materials.
The veterinary API-grade material is controlled not only by assay titration but also by the impurity classes that affect dosage-form stability and animal exposure. Release specifications typically include assay ≥99.5% w/w by anhydrous acid-base titration, water content ≤0.30% w/w by Karl Fischer titration (Ph. Eur. 2.5.12), residue on ignition ≤0.05% w/w (Ph. Eur. 2.4.14), heavy metals ≤10 mg/kg (Ph. Eur. 2.4.8), related substances total ≤0.30% area by gas chromatography (Ph. Eur. 2.2.28), and residual solvents restricted to Class 3 solvents ≤0.50% w/w (Ph. Eur. 2.4.24). Technical-grade material may contain water up to 1.0% w/w and variable amounts of ammonia and higher-boiling oligomeric amines; these components increase the likelihood of colour development in aqueous solutions and extractables formation in sterile packaging. For injectable manufacturing, the API-grade impurity profile reduces particulate risk during terminal steam sterilisation at 121°C for 15 min and improves compatibility with multi-dose rubber stoppers.
| Parameter | Release Limit | Method |
|---|---|---|
| Assay, anhydrous | ≥99.5% w/w | Ph. Eur. 2.2.20 |
| Water content | ≤0.30% w/w | Ph. Eur. 2.5.12 |
| Residue on ignition | ≤0.05% w/w | Ph. Eur. 2.4.14 |
| Heavy metals | ≤10 mg/kg | Ph. Eur. 2.4.8 |
| Related substances, total | ≤0.30% area | Ph. Eur. 2.2.28 |
| Residual solvents | Class 3, ≤0.50% w/w | Ph. Eur. 2.4.24 |
| Ammonia | ≤0.05% w/w | in-house headspace GC |
| pH, 100 g/L aqueous solution | 11.0–12.5 | Ph. Eur. 2.2.3 |
Dry blending of free-base ethylene diamine into tablets, capsules, and powders follows an adsorption principle rather than conventional liquid dispersion. Direct introduction of the free base into a bin blender at levels above 2.5% w/w can generate localised wet films on microcrystalline cellulose or dibasic calcium phosphate, causing content uniformity failure and amine volatilisation during subsequent processing. The preferred method is to pre-adsorb the amine onto colloidal silicon dioxide at an amine-to-silica mass ratio of 1:2 to 1:4 under nitrogen, then transfer the adsorbate to a low-shear tumble blender operating at 15–25 min−1 for 10–15 min. Granulation with an ethylenediamine acid addition salt, rather than the free base, reduces vapour loss in high-shear mixers; wet mass moisture endpoint is commonly held at 8%–15% w/w before fluid-bed drying at inlet air 45–55°C. Final loss on drying for capsule mixtures is set at ≤1.5% w/w because residual moisture accelerates gelatin shell embrittlement and amine migration into the shell matrix. Tablet lubricant selection is restricted; magnesium stearate is used at ≤0.75% w/w because higher levels can retard dissolution of the acid addition salt in aqueous media. Content uniformity is assessed against Ph. Eur. 2.9.40; an acceptance value ≤15 is applied.
Capsule filling of ethylenediamine salt granulates is preferably conducted on a dosator machine or tamping pin machine with relative humidity ≤45% RH. Gelatin, hydroxypropylmethylcellulose, and pullulan shell options are acceptable only when fill moisture is below 1.0% w/w; higher moisture promotes shell embrittlement and pinhole formation. Tablet compression is carried out with a main compression force of 8–18 kN on a rotary press; ethylenediamine dihydrochloride granulates exhibit adequate compressibility when blended with microcrystalline cellulose and crospovidone at 2%–5% w/w. Tablet hardness is maintained at 60–100 N for immediate-release formulations, while disintegration testing is performed according to Ph. Eur. 2.9.1; a disintegration time ≤15 min is expected for film-coated tablets containing the acid addition salt. For dry powders intended for reconstitution, the acid addition salt is milled and sieved to a particle size not more than 150 µm; this particle size prevents caking. The powder is then filled under nitrogen with a desiccant sachet.
Ethylenediamine is used in injectable solutions primarily as a pH regulator, buffering component, or counter-ion source, but free-base addition to a near-neutral parenteral matrix is not recommended without a controlled acid addition step. The molecule has two conjugate-acid pKa values near 10 and 7, placing its buffer capacity across the pH 7.0–10.0 region. A 10% w/v aqueous solution can exceed pH 11.0; lowering the pH to 5.0–6.0 requires two molar equivalents of hydrogen chloride per mole of ethylenediamine, forming ethylenediamine dihydrochloride (molecular mass 133.02 g/mol). The neutralisation is exothermic and is carried out in a jacketed 316L vessel with acid addition at 2.0–5.0 mL/min per kg batch, jacket temperature 15–25°C, and continuous nitrogen sparging at 0.5–1.0 L/min. Uncontrolled addition can produce local temperature excursions above 60°C, accelerating oxidative colour formation and reducing assay recovery. The resulting dihydrochloride solution is stable under acidic pH but will absorb atmospheric carbon dioxide if held unsealed; carbamate or carbonate adducts may then form, producing pH drift and visual haze. For terminally sterilised products, the bulk solution is filtered through a 0.22 µm polyvinylidene fluoride membrane before autoclaving at 121°C for 15 min. Compatibility with chlorobutyl stoppers must be verified because residual amine can accelerate mercapto-compound leachables. Sterile filtration of an unbuffered free-base solution above pH 9.0 is not recommended because elevated pH can promote Type I borosilicate glass delamination during long-term storage. Published data for the specific stopper formulation and fill volume should be generated for each container closure system.
Because the free base has sufficient vapour pressure to produce nuisance odour at processing temperatures, high-shear mixing of open tanks is avoided above 30°C. Closed handling with local exhaust ventilation and real-time ammonia monitoring at ≤10 ppm is used in manufacturing suites; operator exposure limits are enforced according to local worker exposure standards. Ethylenediamine dihydrochloride is preferred for injectable formulations because it is a crystalline solid with lower volatility and a defined melting range, but it is hygroscopic and must be stored in sealed containers below 40% RH.
Oral solutions, drinking-water concentrates, and premix powders use the acid addition salt more frequently than the free base because free-base ethylenediamine produces an objectionable odour and raises pH beyond the stability range of many antibiotic and vitamin combinations. For solution concentrates, the dihydrochloride salt is dissolved in purified water at 25–35°C; pH is adjusted to 4.5–6.5 with hydrochloric acid; sodium metabisulfite is added at 0.05%–0.20% w/v only where oxidative degradation data support its use. The solution is filtered through a 0.45 µm membrane and filled under nitrogen. In medicated premix powders, the amine-containing component is dry-coated onto lactose or dextrose monohydrate before addition to the bulk mixture to limit hygroscopic bridging in silos. Ethylenediamine-containing premixes are incompatible with acidic carriers without prior neutralisation because the free base reacts with acid excipients and releases heat, creating localised moisture uptake.
Because ethylenediamine is corrosive and can provoke dermal and respiratory sensitisation, equipment cleaning after batch use is a critical parameter in shared veterinary manufacturing facilities. Visible clean is insufficient because thin amine films on stainless steel remain odorous below 1.0 µg/cm². Swab sampling from 316L tanks, granulator bowls, and tablet press feed frames is assayed by ion chromatography or gas chromatography after derivatisation. A common acceptance criterion is ≤5.0 µg/cm² on product-contact surfaces, with rinse water conductivity not more than 2.0 µS/cm above feed-water conductivity. Ethylenediamine residues are alkaline and can reduce the dissolution rate of pH-sensitive veterinary formulations; therefore, cleaning validation includes pH measurement of the final rinse fraction. Published data for a specific facility and product sequence are limited, and site-specific carryover calculations are required on the basis of the lowest permitted daily exposure of the next product.
Compared with monoethanolamine, ethylenediamine has two primary amine groups, permitting mono- or dihydrochloride salt formation and stronger transition-metal complexation; however, monoethanolamine is less hygroscopic, and published stability data for veterinary oral solutions may be more extensive. Compared with piperazine, ethylenediamine offers a wider aqueous pH-modifying range and can be used in premix acid addition salts, but piperazine is a crystalline solid and exhibits lower vapour loss during dry blending. These differences are summarised in the following comparison.
| Attribute | Ethylene Diamine Veterinary Grade | Monoethanolamine | Piperazine |
|---|---|---|---|
| Physical state at 20°C | Hygroscopic liquid | Hygroscopic liquid | Crystalline solid |
| Amine groups per molecule | 2 | 1 | 2 |
| Primary pH-modifying range | 7.0–10.0 | 8.5–10.5 | 4.0–6.0 and 8.5–10.0 |
| Hygroscopicity | High | Moderate | Low |
| Veterinary API release controls | Water ≤0.30%, heavy metals ≤10 mg/kg, residual solvents Class 3 | Water ≤0.20%, heavy metals ≤10 mg/kg | Water ≤0.50% w/w for crystalline grade |
| Preferred dosage-form use | Acid addition salt solutions, premixes, granules | pH adjustment in topical preparations | Anthelmintic active intermediate, solid dosage forms |
Bulk handling of ethylene diamine veterinary grade requires nitrogen blanketing in tanks and drums to exclude carbon dioxide and moisture. Carbon dioxide absorption forms carbamate salts that appear as white turbidity in aqueous systems and can reduce assay. During transfer from bulk storage to day tanks, a closed loop with dry nitrogen at 0.1–0.3 bar overpressure is used; rotary lobe pumps with PTFE seals are preferred over centrifugal pumps because slip flow at high differential pressure can increase the liquid temperature and odour release. The product has a flash point near 38°C (closed cup); therefore, pumping is conducted in electrically classified areas according to local zone classification. For granulation, the liquid is introduced through a peristaltic pump into the high-shear mixer at a rate not exceeding 0.5% w/w of dry batch mass per minute to avoid overwetting. Drying end-point is verified by loss on drying at 105°C for 10 min; a final moisture content ≤1.5% w/w is targeted for tablet compression, while capsule filling may require ≤1.0% w/w. Sieve analysis of the dried granulate is checked against Ph. Eur. 2.9.12 to ensure the fraction below 75 µm is not more than 25% w/w, because excessive fines increase amine odour and dust exposure.
Storage and handling constraints apply across all dosage-form sequences. Ethylenediamine is hygroscopic and reacts with atmospheric carbon dioxide; therefore unopened containers are stored at 15–25°C under nitrogen and used within 24 months from release. Once opened, a drum is resealed under nitrogen and consumed within 7 days when storage is in high-humidity environments exceeding 60% RH. Pre-drying of excipients is required when relative humidity exceeds 60% during dry blending. The liquid should not be combined with nitrites, aldehydes, acid anhydrides, acyl chlorides, or oxidising acids because these can generate hazardous reaction products. Equipment contact surfaces should be 316L stainless steel or high-density polyethylene; carbon steel is avoided because amine-catalysed corrosion can release iron into the formulation.
