| HS Code | 250663 |
| Chemical Name | Carbon Dioxide |
| Cas Number | 124-38-9 |
| Molecular Formula | CO2 |
| Molecular Weight | 44.01 g/mol |
| Veterinary Grade | Complies with veterinary pharmacopoeial specifications |
| Physical State | Colorless, odorless gas or solid (dry ice) depending on handling |
| Solubility | Soluble in water; forms carbonic acid |
| Purity | Typically ≥ 99.5% (veterinary grade) |
| Sterility | Suitable for parenteral use when formulated as gas or in solution |
| Storage Conditions | Store in tightly sealed compressed gas cylinders or appropriate containers; avoid heat and open flame |
As an accredited Caebon Dioxide 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 | Carbon Dioxide Veterinary Grade API is supplied in tamper-evident, pharmaceutical-grade sealed containers, ensuring purity and stability. Quantity: 10 kg net. |
| Container Loading (20′ FCL) | Carbon Dioxide Veterinary Grade API is stowed as a 20′ FCL, using secure, ventilated packaging to ensure safe, stable transport. |
| Shipping | Ship as a temperature-controlled, sealed veterinary-grade API. Use moisture-resistant, tamper-evident packaging to preserve stability across dosage forms. Comply with all applicable transport regulations for pharmaceutical substances, including proper documentation and labeling. Ensure secure handling, protection from direct sunlight and extreme temperatures, with traceability for quality assurance. |
| Storage | Store Carbon Dioxide Veterinary Grade API in sealed, approved pressure-rated cylinders or cryogenic containers, upright and firmly secured. Keep in a cool, well-ventilated area away from heat sources, open flames, and direct sunlight. Maintain temperature below 52°C and protect from physical damage. Ensure valves are capped and area is dry, clearly labelled, and free from incompatible materials. |
| Shelf Life | Shelf life is 24 months from manufacture date when stored under recommended conditions in sealed original containers; do not use after expiry. |
In veterinary oral powder and premix packaging lines, carbon dioxide veterinary grade API is metered into the nitrogen flush upstream of the horizontal form-fill-seal sealing station. The pack headspace addition ratio is controlled at 10–25% v/v CO₂ in nitrogen, with residual oxygen held below 2.0% v/v and sealing-zone relative humidity below 30% RH at 20–25°C. This prevents oxidative degradation of unsaturated fatty acid carriers and vitamin A, D3, and E premixes during 24-month shelf-life storage. Finished product types include medicated premixes, oral granules, and soluble powders packed in aluminum-foil-lined bags; the CO₂ partial pressure stabilizes the headspace volume and limits carbonyl-amine browning reactions. The gas is blended through calibrated mass flow controllers with ±0.5% full-scale accuracy, and package leakers are rejected by in-line oxygen sensing. The compendial acceptance is anchored to the current USP–NF Carbon Dioxide monograph and Ph. Eur. 0379; packaging operations follow 21 CFR Part 225 for medicated feed premixes and 21 CFR Part 211 for veterinary drug products. At CO₂ concentrations above 30% v/v with residual moisture above 35% RH, carbonic acid formation at foil surfaces can initiate pinhole corrosion; line stops longer than 15 minutes require nitrogen purge before sealing is resumed.
| Finished product type | CO₂ in headspace | Residual O₂ upper limit | Sealing zone RH |
|---|---|---|---|
| Soluble oral powder | 10–15% v/v | 2.0% v/v | 30% RH |
| Medicated premix | 15–25% v/v | 2.0% v/v | 35% RH |
| Oral granules | 10–20% v/v | 1.5% v/v | 30% RH |
Dissolved carbon dioxide concentration in water for injection is governed by partial pressure, temperature, and bicarbonate buffering. In aseptic filling of veterinary injectable solutions, carbon dioxide veterinary grade is passed through a 0.2 µm sterilizing-grade filter and sparged into a jacketed stainless-steel mixing vessel at 0.5–2.0 L/min per 100 L solution until the in-line pH probe records 6.8–7.2 at 20–25°C. The addition ratio is endpoint-controlled rather than fixed by weight, because buffer capacity of the active ingredient and counterions shifts the dissolved CO₂ equilibrium. Over-sparging depresses pH below 6.5, causing precipitation of weakly basic actives; under-sparging leaves headspace oxygen above 1.0% v/v and accelerates oxidation of sulfhydryl-containing compounds. Aseptic filling lines use a CO₂ blanket at 0.5–1.0 L/min per single-head peristaltic filler with in-line pO₂ measurement. Compliance standards include EudraLex Volume 4 Annex 1 for sterile manufacture, USP 71 sterility testing, USP 788 particulate matter, and Ph. Eur. 0379. Terminal products are sterile injectable solutions and oil-in-water emulsions for cattle, swine, and companion animals. Without a heated two-stage regulator, adiabatic expansion at cylinder withdrawal rates above 10 L/min can produce regulator freeze-up and batch pH drift; for drug substances with pKa values above 7.5, carbon dioxide sparging may not reach the target pH without excessive gas use.
Heat-sensitive veterinary APIs with melting points below 120°C are processed by supercritical antisolvent or rapid expansion of supercritical solutions using carbon dioxide veterinary grade at 40–60°C and 100–250 bar. The CO₂-to-drug solution mass ratio is maintained at 10:1–50:1 through a coaxial nozzle with inner diameter 0.2–0.5 mm; drug solution flow rates are 0.5–5.0 mL/min, and CO₂ flow rates are 20–100 g/min. Particle size is controlled by nozzle pressure drop and antisolvent-to-solvent ratio rather than by post-milling sieving alone. Products are collected in a cyclone separator at 40–50°C and residual solvent is reduced to ICH Q3C limits. Compliance standards include USP 429 laser diffraction, USP 811 powder fineness, 21 CFR 211.110 in-process sampling, and the current USP–NF Carbon Dioxide monograph. Terminal finished product types are micronized oral powders, tablet granules, and capsule fills for antiparasitic and anti-inflammatory veterinary actives. Published data for specific veterinary molecule solubility in supercritical CO₂ is limited; pre-screening of solubility and melting point is required before parameter scale-up. The process is not suitable for APIs soluble in supercritical CO₂ above 5 mg/g or for thermolabile actives with degradation onset below 40°C.
Carbon dioxide euthanasia is regulated not as a dosage form excipient but as an active gas; handling falls under occupational exposure and animal welfare statutes rather than pharmaceutical dosage-form GMP. In controlled systems for rodents, carbon dioxide veterinary grade is introduced at a displacement rate of 30–70% of chamber volume per minute until the chamber concentration reaches 70–80% v/v; exposure is maintained for at least 5 minutes after respiratory arrest. For suckling pigs, the chamber is pre-charged to 80–90% v/v CO₂ and exposure time is 100–120 seconds under EU Regulation (EC) No 1099/2009 Annex I Chapter II; poultry applications use two-phase gas mixtures with induction at 40–60% v/v CO₂ in air and terminal exposure at 80–90% v/v CO₂. Gas delivery hardware includes a high-pressure cylinder manifold conforming to ISO 9809-1, a two-stage stainless steel regulator, a thermal mass flow controller, a chamber exhaust scrubber, and continuous CO₂/O₂ analyzers. The addition ratio is not a formulation percentage but a target chamber concentration with displacement rate; batch-to-batch variance is controlled by cylinder changeover and flow verification with a calibrated thermal mass flow meter. Compliance standards include AVMA Guidelines for the Euthanasia of Animals: 2020 Edition and EU Regulation (EC) No 1099/2009 Annex I Chapter II. Terminal application types are controlled atmosphere euthanasia systems for laboratory rodents, poultry, and suckling pigs. Pre-filled chambers are contraindicated for conscious animals where stepwise induction is required by institutional animal care and use protocols; CO₂ concentrations above 70% v/v are aversive and require prior sedation when species-specific protocols mandate it. Operator exposure must remain below 5000 ppm as an 8-hour time-weighted average.
| Species/application | Target CO₂ concentration | Displacement rate | Minimum holding time |
|---|---|---|---|
| Laboratory rodents | 70–80% v/v | 30–70% chamber volume/min | 5 min after respiratory arrest |
| Suckling pigs | 80–90% v/v | pre-fill or 20–30% chamber volume/min | 100–120 s |
| Poultry | 40–60% v/v induction; 80–90% v/v terminal | two-phase ramp | 2–4 min after collapse |
When oxygen-sensitive veterinary actives are filled into hard gelatin or HPMC capsules, carbon dioxide veterinary grade is blended with nitrogen at 5–15% v/v CO₂ and introduced into the hopper and dosing disc zone at 1–3 L/min per station. The objective is to maintain residual oxygen below 1.0% v/v at capsule closure, because turbulent powder displacement can raise headspace oxygen to 8–12% v/v on standard filling lines. Carbon dioxide is denser than nitrogen and accumulates in the lower hopper cone, but it is used as a mixture to avoid excessive moisture displacement from gelatin capsule shells; pure CO₂ at 25°C and 40% RH can cause shell brittleness and cap/body separation. The addition ratio is verified by non-dispersive infrared CO₂ analyzers and electrochemical oxygen sensors at the filler outlet. Compliance standards include 21 CFR 211.94 for drug product containers and closures, 21 CFR 211.110 for in-process sampling, and ISO 8573-1 for compressed gas purity. Terminal finished product types are hard gelatin capsules, oral powders, and granule-filled capsules for companion animal and swine therapeutics. Batch records must record cylinder pressure, flow rate, and O₂ readings at start, middle, and end of the filling campaign.
The bicarbonate buffer system in medicated drinking water is manipulated by injecting carbon dioxide veterinary grade through a static in-line mixer at 0.3–1.2 g CO₂ per liter of finished solution, targeting pH 5.8–6.4 in the distribution tank. This pH window stabilizes acid-labile veterinary actives such as some tetracyclines and reduces free ammonia volatility in poultry houses; however, over-acidification below pH 5.5 can damage galvanized drinker lines and increase corrosion at copper fittings. The injection point is upstream of the medication proportioner, and pH is monitored with a temperature-compensated probe in a bypass loop. Carbon dioxide is delivered from a liquefied gas cylinder through a heated regulator to prevent freeze-up, and a check valve prevents backflow contamination of the water source. Compliance standards include Ph. Eur. 0379 for gas quality, EU Regulation (EC) No 1831/2003 for feed and water additives, and local veterinary prescription requirements for medicated water. Terminal finished product types are acidified drinking water stock solutions and continuously proportioned medicated water for swine and poultry. The process is not appropriate for closed-loop recirculation systems with copper heat exchangers, because long-term carbonic acid exposure at pH below 6.0 accelerates cupric ion leaching; published data for specific line metallurgy is limited.
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Caebon Dioxide Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is supplied as a pharmacopeial-grade liquefied compressed gas. The chemical identity is carbon dioxide, CAS 124-38-9, molar mass 44.009 g mol⁻¹, critical temperature 31.1 °C, and critical pressure 7.38 MPa. The spelling “Caebon Dioxide” is retained from the trade listing; it does not denote a chemical form distinct from carbon dioxide. At standard conditions the substance is a gas, so the tablet, capsule, powder, granule, and premix designations in the product title are not direct solid-form incorporations of CO₂. The veterinary-grade API designation applies to pharmaceutical gas release, cylinder preparation, and use as a gaseous active or process gas in veterinary manufacturing. No universal model number is assigned under Ph. Eur. 0375 or USP Carbon Dioxide; commercial grade codes are producer-specific. Cylinder outlets are normally configured to CGA 320, and transport classification is UN 1013, Class 2.2. The product is not interchangeable with liquid carbon dioxide for fire suppression or beverage carbonation unless the receiving veterinary facility has verified cylinder cleaning and analytical release status.
The release specification for carbon dioxide used in veterinary applications is derived from Ph. Eur. 0375 and USP Carbon Dioxide. A dedicated veterinary monograph does not currently exist; therefore, batch release for the Caebon Dioxide Veterinary Grade designation is performed against the human medicinal gas purity envelope. The assessment of veterinary suitability uses the same chemical purity, water, carbon monoxide, sulfur compound, and nitrogen oxide thresholds, with additional documentation of cylinder preparation and residue testing when the receiving site requires it. The values summarized in Table 1 are quoted from the current edition of Ph. Eur. 0375; confirming against the applicable local pharmacopeial edition is mandatory before release.
| Parameter | Reference method / standard | Acceptance criterion |
|---|---|---|
| Assay | Ph. Eur. 0375 gas volumetric / GC | ≥99.5% v/v |
| Carbon monoxide | Ph. Eur. 0375 | ≤5 ppm V/V |
| Water | Ph. Eur. 0375 | ≤0.05% m/m |
| Sulfur dioxide and other sulfur compounds | Ph. Eur. 0375 | ≤5 ppm V/V |
| Nitric oxide and nitrogen dioxide | Ph. Eur. 0375 | ≤2 ppm V/V |
Analytical release for veterinary receiving sites typically includes gas chromatography with thermal conductivity detection for assay and carbon monoxide, plus colorimetric detector tubes for sulfur and nitrogen oxides. Cylinder-to-cylinder non-volatile residue is assessed by evaporation of a known gas volume through a filter; deviations are typically due to cylinder preparation rather than source gas quality. The certificate of analysis for Caebon Dioxide Veterinary Grade API should list cylinder serial number, filling date, and expiry date under current good distribution practice.
Production-scale withdrawal from high-pressure liquefied cylinders is constrained by latent heat of vaporization. At 20 °C, the equilibrium vapour pressure of liquefied carbon dioxide is approximately 5.7 MPa. Vapour-space take-off is practical only at low demand. Sustained withdrawal from the liquid phase without supplemental heat reduces cylinder pressure below the regulator setpoint and can cause regulator seat freezing. Poultry and swine euthanasia systems operating at continuous flow above 10 L/min therefore require heated regulators, vaporizers, or manifolded cylinders with automatic changeover. Published field data for exact freeze-off thresholds in veterinary piping are limited; cylinder fill density, ambient temperature, and duty cycle control the minimum operating temperature. In rodent chamber use, the AVMA Guidelines for the Euthanasia of Animals: 2020 Edition specify a displacement rate of 10–30% charged chamber volume per minute; rates above this range are described as aversive before loss of consciousness. Carbon dioxide is heavier than air, with vapour density approximately 1.53 relative to air, so low-point extraction is required during cylinder changeover and chamber maintenance.
Cylinder packages for Caebon Dioxide Veterinary Grade API use high-pressure liquefied gas valves with pressure relief devices rated for the cylinder service pressure. The outlet connection is normally CGA 320. Regulator bodies should be constructed from 316L stainless steel or naval bronze with polytetrafluoroethylene or polyimide seats, because carbon dioxide plus trace water forms carbonic acid and accelerates corrosion of unprotected carbon steel internals. Elastomeric seats must be qualified for the minimum temperature encountered during expansion; nitrile rubber seat embrittlement is a documented failure mode in high-flow gas delivery. Check valves and flashback arrestors are not interchangeable with oxygen service. Downstream piping should be selected for a design pressure above 6.0 MPa and a design temperature below −30 °C at the regulator outlet. The gas is not an oxidizer, but it can displace oxygen in confined spaces. Oxygen sensors rather than carbon dioxide detectors are used for personnel protection because hypoxia can develop before carbon dioxide alarms reach the occupational exposure limit in leak scenarios. The OSHA 8-hour permissible exposure limit for carbon dioxide is 5,000 ppm, the NIOSH short-term exposure limit is 30,000 ppm, and the NIOSH immediately dangerous to life or health value is 40,000 ppm.
The tablet, capsule, powder, granule, and premix designations in the product listing are not fulfilled by dry mixing of gaseous CO₂. In these solid dosage forms, carbon dioxide is generated in situ through the acid–base reaction of a carbonate or bicarbonate salt with a food-grade acid, typically citric acid or tartaric acid. The role of gaseous CO₂ is limited to headspace inerting, storage under a protective atmosphere, and vessel blanketing during granulation. In effervescent granulation, the reaction rate depends on residual moisture and the particle size distribution of the acid and carbonate components; published data for veterinary-specific residual moisture thresholds in this configuration are limited. The gas is not a binder, disintegrant, or filler. Dissolved carbon dioxide establishes a carbonic acid–bicarbonate equilibrium with pKa₁ 6.35 at 25 °C; unbuffered aqueous systems saturated at atmospheric pressure approach pH 3.9. This pH is unsuitable for most direct incorporation into tablets or capsules without a buffering system.
Carbon dioxide is not recognized as a therapeutic injectable agent in the major veterinary pharmacopeias. Injectable application is confined to pH modification and headspace filling, where solubility and carbonic acid equilibrium are exploited. The gas dissolves in water at approximately 1.7 g/L at 20 °C and 101.3 kPa. Unbuffered aqueous solutions therefore require buffer capacity to maintain physiological pH 7.35–7.45. When the gas contacts an injectable solution, it must be sterile-filtered through a 0.22 µm hydrophobic membrane before use; filter validation follows the applicable pharmacopeial general chapter. Published data for formulation-specific CO₂ solubility in veterinary injectable matrices containing surfactants and co-solvents are limited.
Carbon dioxide differs from nitrogen and argon in three operational properties: it forms carbonic acid in aqueous systems, it is more water-soluble, and it has a pungent odour that influences animal stress responses. Nitrogen is relatively insoluble and is used for oxygen displacement without pH shift; argon is denser than nitrogen but pharmacologically inert. Neither nitrogen nor argon provides the rapid narcosis and respiratory drive associated with carbon dioxide at high concentrations. Compared with isoflurane, carbon dioxide requires no precision vaporizer, but it is unsuitable for inhalant anaesthesia because its narcotic effect is inconsistent and is preceded by acidosis and dyspnea. Table 2 summarizes these differences. The selection of carbon dioxide for euthanasia or process inerting must be made under institutional animal-use protocols and occupational exposure assessment; it is not interchangeable with anaesthetic vapours.
| Agent | CAS number | Reference pharmacopeial status | Operational difference |
|---|---|---|---|
| Carbon dioxide | 124-38-9 | Ph. Eur. 0375, USP Carbon Dioxide | Forms carbonic acid; pungent; heavier than air; used in controlled euthanasia |
| Nitrogen | 7727-37-9 | NF Nitrogen | Relatively insoluble; no pH shift; used for inerting and oxygen displacement |
| Argon | 7440-37-1 | USP Argon | Denser than nitrogen; pharmacologically inert; limited euthanasia evidence |
| Isoflurane | 26675-46-7 | USP Isoflurane | Requires calibrated vaporizer and scavenging; occupational exposure limit applies |
Storage and incompatibility boundaries for Caebon Dioxide Veterinary Grade API are dominated by the gas’s reactivity with aqueous bases and amines. Closed systems must be protected against backflow of alkaline liquids, because rapid absorption of CO₂ into sodium hydroxide or potassium hydroxide solutions can create subatmospheric pressure and draw liquid into the gas manifold. The gas should be kept from primary and secondary amines in anhydrous systems; carbamate formation can alter pH and generate insoluble degradation products. In tablet and capsule packaging, headspace replacement with CO₂ is limited by the moisture barrier of the package web; moisture ingress dissolves the gas, lowers interfacial pH, and can accelerate hydrolytic degradation of acid-labile actives. Barrier selection should be tested according to ASTM F1249. Carbon dioxide should not be manifolded to the same purge line as oxidizing gases without dedicated check valves and should not be used in unvented storage areas where cylinder leak cross-contamination may create a hazardous atmosphere.
