Vitamin K Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is supplied as menadione sodium bisulfite complex, product code VK3-MSBC-96/VET, with a white to pale-yellow crystalline powder appearance and assay on dried basis not less than 96.0%. The material is manufactured under EU GMP Part II / ICH Q7 and is released with route-specific controls for tablet, capsule, powder, granule, premix, injection, and oral/parenteral solution manufacture. The product differs from feed-grade menadione sources principally in bacterial endotoxin control (≤5.0 EU/mg for oral grades, ≤0.5 EU/mg for injectable grades), residual solvent testing according to Ph. Eur. 2.4.24 / USP <467>, and elemental impurity limits aligned with ICH Q3D Option 1. Water solubility of the sodium bisulfite complex is typically above 50 g/100 mL at 25°C, enabling direct use in aqueous solutions and wet granulation; the free menadione base is practically insoluble in water and is not supplied for aqueous veterinary formulations. The API can be ordered with particle-size targets of D90 ≤150 µm for injectable compounding, D90 ≤250 µm for direct-compression tablet operations, and D90 ≤500 µm for premix and granular feed applications.

What Distinguishes This Veterinary API from Feed-Grade Menadione Sources?

The primary distinction is compendial control of impurities, solvents, and endotoxin rather than the menadione backbone itself. Feed-grade menadione sodium bisulfite powders are often standardised as menadione activity equivalents and can be supplied on mineral carriers with silica, calcium carbonate, or wheat bran; their content uniformity can vary by ±10% relative to label claim at bulk silo discharge. The veterinary API is released as a single chemical entity on dried basis by UV spectrophotometry and HPLC, with total related substances not more than 1.0% for the oral/premix grade and not more than 0.5% for the injectable grade. Residual acetone and isopropanol are controlled below 0.5% w/w total, whereas feed-grade sources may not report solvent residues. Menadione nicotinamide bisulfite or dimethylpyrimidinol bisulfite derivatives are not interchangeable with this sodium bisulfite complex in aqueous injection formulas because their solubility and pH profiles differ. The sodium bisulfite moiety imparts measurable antioxidant capacity in solution, but aqueous preparations remain oxygen-sensitive above pH 6.5. For tablet and capsule manufacture, the crystalline API is typically dry granulated after blending with microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. In production-scale roller compaction, a 0.8–1.2 mm screen and 20–30 kN roll force produce granules with bulk density 0.55–0.75 g/mL; this range reduces segregation and allows consistent filling of hard-gelatin capsules. At 25±2°C and 60±5% RH, blending beyond 60 min can increase fines below 75 µm by 4–7 percentage points, raising capping tendency in tablet compression. Endpoint control should therefore include loss on drying below 1.0% and near-infrared moisture monitoring if the processing area exceeds 60% RH. Direct compression without granulation is possible only when the supplied API particle-size distribution is tight: D10 ≥30 µm, D50 90–130 µm, and D90 ≤250 µm. Drug loading above 25% w/w in a tablet core requires glidant addition at 0.5–1.0% w/w to control electrostatic adhesion on tooling.

When Sterile-Injection Workflows Require Endotoxin Control and API Pre-Treatment

Injectable-grade menadione sodium bisulfite is released with bacterial endotoxins ≤0.5 EU/mg by Ph. Eur. 2.6.14 kinetic chromogenic method. Bulk solutions are compounded at 20–25°C in water for injection, then filtered through 0.22 µm PVDF membrane; dissolution of the API should be complete within 5 min at 200 rpm in a baffled stainless-steel vessel. Terminal steam sterilisation at 121°C for 15 min may produce potency losses of 2–5% if dissolved oxygen exceeds 2 mg/L; nitrogen sparging to ≤0.5 mg/L dissolved oxygen and pH adjustment to 5.0–5.5 with 0.1 M sodium hydroxide generally maintain loss below 1.5%. Phosphate buffering at 10–20 mM is preferred over citrate because citrate can reduce filter flux at low temperature. Solutions containing calcium gluconate or magnesium sulfate require compatibility screening; sulfate/calcium precipitation and pH drifting above 6.5 are the primary failure modes observed in veterinary injectable compounding.

Aqueous Solution Stability and Light-Sensitivity Limits

Menadione sodium bisulfite complex in aqueous solution is light-sensitive and degrades by first-order kinetics under 365 nm ultraviolet exposure. Amber polyethylene terephthalate containers reduce photolytic loss to <2% over 72 h at 25°C; clear borosilicate glass can lose 8–12% in the same period. The pH of a 1% w/v solution should be maintained between 4.0 and 6.5; above 6.5, oxidation accelerates and colour shifts from pale yellow to brown. Disodium EDTA at 0.01% w/v is suitable for metal-catalysed oxidation control in oral solutions; sodium metabisulfite may be used only after pH adjustment because it can depress solution pH below 3.5. For multidose oral solutions, preservatives such as methylparaben at 0.18% w/v and propylparaben at 0.02% w/v are typical, but their partition into plastic dosing syringes should be verified by stability testing per VICH GL3. Strong reducing agents such as sodium thiosulfate are incompatible in aqueous solution because they can reduce the quinone and cause precipitation.

Dry-Granulated Premix Processes Achieve Uniform Carryover Control

For medicated premix and granular feed applications, the API is pre-blended with colloidal silicon dioxide at 0.5–1.0% w/w to reduce electrostatic adhesion and then geometrically diluted into a ribbon blender or paddle mixer. Blend uniformity in a 500 kg batch should be verified by sampling 10 points with a coefficient of variation below 10% according to ISO 6497. Segregation is minimised when the API D90 is within 3–5 times the median particle size of the carrier; milling through a 0.8 mm screen prevents nugget formation. If the premix contains choline chloride or trace mineral salts, direct contact with unprotected API should be avoided because free moisture from hygroscopic carriers can exceed 2.0%, accelerating dimerisation of menadione. In such cases, the API is first adsorbed onto microcrystalline cellulose or silica with moisture content below 1.0%. Cleaning validation after batch completion uses a swab limit of 10 mg/m² for menadione sodium bisulfite, verified by HPLC-UV. In contrast to synthetic phytomenadione (vitamin K1), which remains the molecule used for intravenously administered oil-in-water emulsions, menadione sodium bisulfite complex provides water-soluble dosing without polysorbate-based emulsification. Phytomenadione oral oil solutions typically have viscosity around 25–30 mPa·s at 25°C and may require refrigerated storage in some multidose formulations; the sodium bisulfite complex can be formulated as a clear aqueous solution at 10 mg/mL without organic co-solvents. The pharmacokinetic onset of menadione-derived vitamin K activity is slower than that of phytomenadione in cases of anticoagulant rodenticide poisoning, and veterinary treatment protocols therefore use phytomenadione for acute bleeding emergencies, while menadione sodium bisulfite is used in feed, oral solutions, and preventive supplementation. This product is not a direct substitute for phytomenadione injectable emulsion in emergency anticoagulant reversal. Representative release targets for VK3-MSBC-96/VET by dosage-form route are summarised below.

Parameter	Tablet/Capsule/Powder	Injection	Premix/Oral Solution
Assay, dried basis	96.0–101.0%	97.0–101.0%	96.0–101.0%
Loss on drying	≤1.0%	≤0.5%	≤1.0%
Bacterial endotoxins	≤5.0 EU/mg	≤0.5 EU/mg	≤5.0 EU/mg
Heavy metals, as Pb	≤10 mg/kg	≤5 mg/kg	≤10 mg/kg
Residual solvents total	≤0.5% w/w	≤0.3% w/w	≤0.5% w/w
Particle size D90	≤250 µm	≤150 µm	≤500 µm
Bulk density	0.55–0.75 g/mL	0.60–0.80 g/mL	0.50–0.70 g/mL
Hausner ratio	≤1.25	≤1.20	≤1.30
pH, 1% aqueous solution	4.0–6.5	5.0–6.5	4.0–6.5

Release documentation includes a compliance matrix linking test methods to recognised pharmacopoeial and veterinary standards.

Standard/Method	Application	Representative Criterion
Ph. Eur. 2.6.14	Bacterial endotoxins, injectable grade	≤0.5 EU/mg
USP <85>	Bacterial endotoxins, oral/premix grade	≤5.0 EU/mg
USP <467> / Ph. Eur. 2.4.24	Residual solvents	Class 1 absent, total ≤0.5% w/w
ICH Q3D Option 1	Elemental impurities	Pb ≤5 mg/kg, Cd ≤2 mg/kg, As ≤2 mg/kg, Hg ≤1 mg/kg
Ph. Eur. 2.5.12	Water semi-micro determination	LOD ≤0.5–1.0% by route
EU GMP Part II / ICH Q7	API manufacturing and distribution	Full batch traceability
ISO 9001:2015	Site quality management	Certified quality system

Packaging for the API is route-specific: oral and premix grades are filled into food-grade LDPE bags within fibre drums with desiccant, while injectable grade is double-bagged in LDPE and sealed in aluminium-laminated foil. Storage below 25°C and protection from light maintain potency within 24 months from release when retest intervals follow ICH Q1A guidance. Opened containers should be re-closed under nitrogen if residual moisture ingress exceeds 0.1% per pack; high-humidity sites should add desiccant units and limit open dwell time to 30 min per transfer.