| HS Code | 753991 |
| Product Type | Trimethoprim (TMP) Veterinary Grade API |
| Chemical Name | 5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine |
| Molecular Formula | C14H18N4O3 |
| Molecular Weight | 290.32 g/mol |
| Cas Number | 738-70-5 |
| Appearance | White or almost white crystalline powder |
| Solubility | Slightly soluble in water, soluble in dilute mineral acids and chloroform, sparingly soluble in ethanol |
| Melting Point | 199-203 degrees Celsius |
| Assay On Dried Basis | 98.0%-102.0% |
| Residual Solvents | Complies with ICH/VICH limits |
| Particle Size | Customizable, typical D50 10-50 micrometers |
| Storage Conditions | Keep in tightly sealed container, protected from light, in a cool dry place |
| Intended Dosage Forms | Tablets, Injections, Capsules, Powders, Granules, Premix, Solutions |
As an accredited Trimethoprime (TMP) 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 | 25kg sealed drum, inner double polyethylene bag, labeled for veterinary-grade Trimethoprim API for diverse dosage forms. |
| Container Loading (20′ FCL) | A 20′ FCL safely loads Trimethoprim Veterinary Grade API in sealed containers, protecting powders, granules, tablets, and premix during transit. |
| Shipping | Trimethoprim veterinary-grade API ships in sealed, UN-approved containers to prevent contamination and moisture exposure. Temperature-controlled logistics and secure cushioning protect powder integrity. Shipments comply with hazardous material regulations, require relevant documentation, and are delivered with tamper-evident seals for safety and regulatory traceability. |
| Storage | Store Trimethoprim Veterinary Grade API in a well-closed, light-resistant container in a cool, dry, well-ventilated area. Protect from excessive heat, moisture, and direct sunlight. Keep away from incompatible substances and food. Ensure container is tightly sealed after use. Recommended storage temperature: below 25°C. |
| Shelf Life | Shelf Life: 3 years from manufacture when stored in original unopened container at controlled room temperature, protected from light and moisture. |
Veterinary oral boluses containing trimethoprim and sulfadiazine at a 1:5 (w/w) potentiation ratio are produced by wet granulation for administration to cattle, sheep and goats. The formulation addition rate places trimethoprim at 20 mg per 1 g bolus and sulfadiazine at 100 mg per 1 g bolus, equivalent to 2.0% and 10.0% w/w respectively. In a 600 L high-shear granulator operating at impeller tip speed 4–6 m/s and chopper speed 1500–3000 rpm, the dry powder blend is wetted with a 5–8% w/w aqueous polyvinylpyrrolidone K30 binder solution to a granulation endpoint of 35–45% w/w water content; the wet mass is passed through a 1.0 mm sieve and dried in a fluid-bed dryer at inlet air 55–60°C until loss on drying is ≤2.0%. Compression on a 27-station rotary tablet press with 20 mm flat-faced bevelled scored tooling is carried out at 12–25 kN to yield hardness 80–150 N and friability <1.0% under Ph. Eur. 2.9.7. Compliance is anchored to Ph. Eur. 2.9.5 for content uniformity, Ph. Eur. 2.9.3 for dissolution, VICH GL18 for residual solvent control, and EU Regulation (EU) No 37/2010, which sets the trimethoprim marker residue at 50 µg/kg in bovine and ovine edible tissues; the sulfadiazine component is assessed under the sum-of-sulfonamides marker residue at 100 µg/kg. Terminal finished product types include scored oral boluses and tablets packed in HDPE jars with desiccant, as well as aluminium/PVC blister strips for smaller ruminant dose units.
Injectable formulations of sulfadoxine and trimethoprim are concentrated aqueous or mixed organic cosolvent systems in which trimethoprim base exhibits a solubility minimum near neutral pH and remains dissolved only through careful pH control or cosolvent loading. The standard addition ratio is 200 mg sulfadoxine and 40 mg trimethoprim per mL, a 5:1 ratio, filled in 100 mL amber type II glass vials. Sulfadoxine is maintained in solution at pH 9.5–10.5, while trimethoprim is held by a propylene glycol/ethanol cosolvent system; the exact cosolvent ratio is batch-specific and verified by HPLC assay because published data for exact proportions across all commercial presentations is limited. During manufacture the API is dispersed in water for injection at 60–70°C, pH is adjusted with sodium hydroxide or hydrochloric acid, and the bulk solution is sterilized by filtration through a 0.22 µm PVDF membrane before aseptic filling under EU GMP Annex 1 conditions. Sterility is verified by Ph. Eur. 2.6.1, bacterial endotoxins by Ph. Eur. 2.6.14, and particulate contamination by Ph. Eur. 2.9.19; residual solvents are controlled under VICH GL18. The primary production bottleneck is precipitation of trimethoprim during temperature cycling; therefore bulk solution temperature is maintained above 25°C until terminal filtration. Terminal finished product types include injectable solution in multidose vials and injectable suspension presentations with reduced cosolvent loading for markets requiring extended action.
Because trimethoprim is practically insoluble in neutral and alkaline water, poultry and swine drinking water formulations are designed around an acidic reconstitution boundary of pH 3.5–4.0. A representative addition ratio is 20 g trimethoprim and 100 g sodium sulfadiazine per 1 kg finished sachet, with 5–10% w/w anhydrous citric acid and 2–5% w/w sodium citrate as buffering carriers. The dry blend is prepared in a 1000 L V-blender at 70–80% fill volume and 20–30 rpm for 15–20 min; blend uniformity is confirmed by near-infrared spectroscopy with active ingredient RSD ≤5.0%. For granulated presentations, a fluid-bed top-spray granulator with inlet air 50–60°C applies a 5% w/w aqueous polyvinylpyrrolidone K25 binder to produce granules between 150 µm and 500 µm. Compliance is anchored to Ph. Eur. 2.6.12 for microbial limits, USP <905> for uniformity of dosage units, VICH GL11 for related substances, and EU Regulation (EU) No 37/2010 for withdrawal period calculation in food-producing species. Terminal finished product types include foil-lined 1 kg sachets, 5 kg pails, and bulk 25 kg drum pack for on-farm dosing pumps.
Canine tablets formulated with trimethoprim and sulfadiazine at a 1:5 ratio require strict content uniformity because the absolute trimethoprim quantity per tablet can fall below 20 mg in the lowest strength. The addition rate for the lowest tablet strength is 20 mg trimethoprim and 100 mg sulfadiazine per tablet, with higher strengths at 40 mg/200 mg and 80 mg/400 mg. Direct compression is not preferred due to API segregation; instead wet granulation with microcrystalline cellulose, lactose monohydrate and pregelatinized starch is conducted in a 200 L high-shear mixer at impeller speed 250–350 rpm and chopper speed 1000–1500 rpm, followed by drying at 50–55°C to LOD ≤2.5%. Compression on a 16-station rotary press using 10 mm round scored tooling at 8–14 kN produces hardness 60–100 N and friability <1.0%. Dissolution testing under USP <711> using Apparatus 2 at 50 rpm in 900 mL 0.1 N HCl at 37 ± 0.5°C applies an acceptance criterion of Q ≥80% at 45 min; content uniformity is assessed by Ph. Eur. 2.9.5 or USP <905>. Regulatory compliance for the United States oral dosage form is referenced to 21 CFR 520.2610, with residual solvents controlled under VICH GL18. Terminal finished product types include scored tablets in aluminium/PVC blister strips and HDPE bottles with child-resistant closures, as well as hard gelatin capsules for compounding pharmacies where permitted.
In equine practice, trimethoprim-sulfadiazine oral paste is produced as a high-viscosity dispersion rather than a solution, because both active substances are present at concentrations that exceed their equilibrium solubility in aqueous vehicles. The paste addition rate places trimethoprim at 6.0% w/w and sulfadiazine at 30.0% w/w, equivalent to 0.6 g and 3.0 g per 10 g paste, maintaining the 1:5 ratio; the paste vehicle contains 10–15% w/w microcrystalline cellulose and 5–8% w/w colloidal silicon dioxide to provide shear-thinning flow. Manufacture uses a vacuum planetary mixer operating at 20–40 rpm under −0.08 MPa to remove entrained air, with the active API pre-blended as a 1:5 trituration through a 0.5 mm screen before addition to the vehicle. Content uniformity is verified by Ph. Eur. 2.9.5 on multiple points along the dosing syringe, and microbial limits by Ph. Eur. 2.6.12; residual solvent status follows VICH GL18. Terminal finished product types include 30 g and 60 g graduated oral dosing syringes, ready-to-use oral paste syringes, and bulk paste for repackaging by veterinary compounding facilities.
For markets where national registration exists, feed premix lines handling trimethoprim and sulfadiazine for swine and poultry are operated as segregated microingredient suites. The premix addition rate is 40 g/kg trimethoprim and 200 g/kg sulfadiazine, intended for dilution into final feed at 2–5 kg/tonne depending on species and withdrawal period requirements. Production uses geometric dilution in a 500 kg ribbon blender with 0.5–1.0% w/w mineral oil added to suppress dust and reduce active migration; cross-contamination carryover is controlled to ≤2.5% of the maximum theoretical carryover under the receiving feed establishment's HACCP plan. Compliance is anchored to EU GMP Part II for active substance handling, VICH GL11 for related substances, and EU Regulation (EU) No 37/2010 for marker residue limits in food-producing species. Terminal finished product types include 25 kg paper bags with PE liner and 5 kg pails for farm use.
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Trimethoprime (TMP) Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is supplied as a crystalline dihydrofolate reductase inhibitor of the 2,4-diaminopyrimidine class. The product is released under four internal designations: TMP-VET-C for direct compression and capsule filling, TMP-VET-M for micronized suspension and wet granulation, TMP-VET-I for sterile injectable and oral solution applications, and TMP-VET-P for medicated premix and granulated feed incorporation. Identity and purity conform to Ph. Eur. 0060 and the USP Trimethoprim monograph. The dried-basis assay window is 98.5–101.0%. Melting point is controlled between 199°C and 203°C, and loss on drying is maintained at ≤0.5%. Production-scale tumble blenders have recorded angle of repose from 38° to 46° for the non-micronized grade at 25°C and 30% relative humidity; this variability requires feed-frame agitation on high-speed rotary tablet presses.
Particle size distribution is the principal variable separating the model grades. Laser diffraction analysis according to ISO 13320:2020 is used with dry dispersion at 0.5 bar. Micronized TMP-VET-M typically shows D90 from 25 µm to 45 µm, which increases surface area for dissolution-limited oral suspensions and wet granulation. TMP-VET-I is controlled to D90 from 10 µm to 20 µm and is jet-milled before release to reduce endotoxin burden and improve filterability in sterile manufacturing. Non-micronized TMP-VET-C with D90 from 120 µm to 180 µm has better flow; however, at residual moisture above 0.5%, cohesive bridges form in hoppers. For direct compression, TMP-VET-C is blended with microcrystalline cellulose and crospovidone. Tablet weight variation remains within ±3% when press speed is below 60 rpm and feed-frame speed is set to 20 min⁻¹. Production-scale rotary press data were recorded at 25 kN precompression and 50 kN main compression force. Above 80 rpm, weight variation exceeds ±5% because of flow limitation, requiring either precompression increment or granulation.
Micronized material presents triboelectric charging at relative humidity below 30%; equipment earthing and humidification to 40–50% are required for consistent capsule filling. Segregation risk in low-shear blenders increases when bulk density differences exceed 0.15 g/mL. TMP-VET-P is therefore manufactured as a densified granule to reduce migration in dry feed premixes; homogeneity in a ribbon blender of 500 kg capacity is verified by sampling 12 points with relative standard deviation below 5%.
| Model | D90 | Bulk density | Endotoxin limit | Dosage form |
|---|---|---|---|---|
| TMP-VET-C | 120–180 µm | 0.42–0.52 g/mL | ≤0.5 EU/mg | Tablets, capsules |
| TMP-VET-M | 25–45 µm | 0.25–0.35 g/mL | ≤0.1 EU/mg | Wet granules, oral suspension |
| TMP-VET-I | 10–20 µm | 0.30–0.40 g/mL | ≤0.05 EU/mg | Injections, oral solutions |
| TMP-VET-P | 90–150 µm | 0.50–0.60 g/mL | ≤0.5 EU/mg | Premix, granules |
Trimethoprim solubility in water at 25°C is approximately 0.4 mg/mL; solubility increases in dilute mineral acid. Oral solution formulations therefore rely on citrate or lactate buffers at pH 3.5–4.5 to maintain concentration. In combination with sulfadiazine or sulfamethoxazole at a 5:1 sulfonamide-to-trimethoprim ratio, sequential inhibition of dihydropteroate synthase and dihydrofolate reductase produces bactericidal activity against susceptible isolates. The sulfonamide component blocks incorporation of para-aminobenzoic acid; trimethoprim prevents reduction of dihydrofolic acid to tetrahydrofolic acid. This combination is described in multiple veterinary monographs, including injectable, oral paste, and tablet preparations for cattle, swine, and companion animals. Published data for residue depletion under VICH GL 49 in minor species remains limited.
Because injectable and oral solution grades cross mucosal or parenteral barriers, low endotoxin is a release criterion. TMP-VET-I is tested by Ph. Eur. 2.6.14 or USP <85> with an internal limit of ≤0.05 EU/mg. Residual solvents are controlled under ICH Q3C; for TMP-VET-I, methanol is limited to 3000 ppm, dichloromethane to 600 ppm, and toluene to 890 ppm. Sterile filtration of aqueous or co-solvent solutions is performed through 0.22 µm polyethersulfone filters; pre-filtration bioburden is maintained below 10 CFU/100 mL. Terminal steam sterilisation at 121°C for 15 min is not generally applied because pH drift and precipitation may occur in buffered solutions; aseptic filtration is the preferred route for parenteral preparation.
Packaging for TMP-VET-I uses double low-density polyethylene liners inside aluminium composite bags under nitrogen; oxygen headspace is below 2%. Pre-drying is required if storage relative humidity exceeds 60%. The material is incompatible with strong oxidising agents and should not be dry-mixed with alkaline sulfonamide salts before pH adjustment. In hard water for oral solutions, high carbonate concentrations may raise pH and reduce solubility; acidification is therefore applied before API addition.
Trimethoprime Veterinary Grade differs from sulfonamide monotherapy in mechanism and resistance selection. Sulfonamides alone inhibit dihydropteroate synthase; trimethoprim alone inhibits dihydrofolate reductase. The combination reduces the emergence of resistant subpopulations when both components remain above the minimum inhibitory concentration throughout the dosing interval. Among related 2,4-diaminopyrimidines, ormetoprim is formulated with sulfadimethoxine primarily in poultry and fish, while baquiloprim has longer tissue retention in cattle and is not approved in all jurisdictions. Pyrimethamine has greater activity against apicomplexan parasites and is not a routine veterinary bacterial therapy. Trimethoprim retains the most extensive pharmacopoeial monograph coverage and residue-control analytical methods, which simplifies regulatory submission. However, published comparative tissue depletion data for minor species under VICH GL 49 is limited.
In vitro, trimethoprim susceptibility should be interpreted according to CLSI VET01S; some enterococci and anaerobes can bypass folate blockade by exogenous thymidine, leading to treatment failure even when the isolate appears susceptible in standard media. This constraint is not shared by most beta-lactam or fluoroquinolone therapies.
Related substances in TMP Veterinary Grade are resolved by HPLC under conditions described in Ph. Eur. 0060 and the USP Trimethoprim monograph. The reporting threshold is 0.05%; specified impurity limits follow the relevant monograph. Sulfated ash is not more than 0.1%. Heavy metals are controlled by Ph. Eur. 2.4.8 with a limit of ≤20 ppm. The API is not sterilised by ethylene oxide, and gamma irradiation is avoided because of radiolytic degradation risk. The following matrix summarises release parameters.
| Parameter | Method/Standard | Limit |
|---|---|---|
| Assay (dried basis) | Ph. Eur. 0060 / USP | 98.5–101.0% |
| Melting point | Ph. Eur. 2.2.14 | 199–203°C |
| Loss on drying | Ph. Eur. 2.2.32 | ≤0.5% |
| Sulfated ash | Ph. Eur. 2.4.14 | ≤0.1% |
| Particle size D90 | ISO 13320:2020 | Model-specific |
| Bacterial endotoxins | Ph. Eur. 2.6.14 / USP <85> | ≤0.05 EU/mg for TMP-VET-I |
| Residual solvents | ICH Q3C | Class 2 Option 1 |
| Heavy metals | Ph. Eur. 2.4.8 | ≤20 ppm |
| Current good manufacturing practice | EU GMP Part II / ICH Q7 | Applicable |
For non-sterile oral grades, total aerobic microbial count is controlled below 100 CFU/g and total combined moulds and yeasts below 50 CFU/g by the supplier. These values align with current good manufacturing practice for non-sterile pharmaceutical starting materials, although the final dosage form monograph or marketing authorisation may impose tighter limits.
Tablet and capsule processing with TMP-VET-C uses direct compression after a 30-minute low-shear blend with lactose monohydrate and sodium starch glycolate. Tablet hardness is maintained between 5 kp and 8 kp for 200 mg tablets; higher compression forces slow disintegration. Wet granulation with TMP-VET-M employs a high-shear granulator with impeller speed 300 rpm and chopper speed 1500 rpm; granule moisture is dried to 1.0–1.5% in a fluid-bed dryer at inlet air 60°C. Dissolution of immediate-release tablets is evaluated in 0.1 M HCl at 37°C with USP <711> apparatus 2 at paddle speed 50 rpm; an internal control of not less than 75% release in 45 min is commonly applied. Medicated premix with TMP-VET-P is diluted with limestone or wheat bran to 20–200 g/kg depending on target species; homogeneity is verified by assay of 10 samples with relative standard deviation below 5%. Injectable solutions are compounded aseptically at pH 3.5–4.5, filtered through 0.22 µm polyethersulfone, and filled under nitrogen. Oral solutions and powders are protected from light in amber HDPE or foil-lined packs because ultraviolet exposure accelerates photodegradation.
