Dasuan Kushen Injection Veterinary Grade API is positioned as a standardised dual-extract powder for downstream formulation in food-producing and companion-animal dosage forms. The material used in the following application profiles is specified as a dry extract with total alkaloids expressed as matrine NLT 1.0% w/w, alliin content NLT 0.3% w/w, loss on drying ≤6.0% w/w, and sulfated ash ≤8.0% w/w. The processing boundaries differ by formulation route: aqueous systems are controlled mainly by dissolved oxygen and pH, dry systems by particle-size segregation and moisture ingress, and feed systems by pelleting temperature and cross-contamination. All application classes below assume that the extract is not sterile and must be subjected to downstream sterilisation or microbial-control steps appropriate to the final dosage form.

Injectable solutions for swine and cattle are compounded at an API loading of 0.5–1.0 g/100 mL, corresponding to 5–10 mg/100 mL matrine and 1.5–3.0 mg/100 mL alliin. The vehicle is prepared by dissolving 0.55 g/100 mL sodium chloride and 0.05 g/100 mL sodium metabisulfite in Water for Injection purged with nitrogen until dissolved oxygen drops below 0.5 mg/L. The API is pre-milled to D90 ≤75 μm and added under high-shear mixing at 12,000 rpm for 15 min. The pH is adjusted to 6.0–6.4 with 0.1 M hydrochloric acid, after which the bulk is clarified through a 0.45 μm polyethersulfone membrane. Thermal sterilisation at 121°C for 15 min is valid only when total extract concentration does not exceed 1.0% w/v; above this concentration, aseptic filtration through a 0.22 μm PVDF membrane is required because alliin degradation exceeds 5% under terminal heat load. Terminal products are 10 mL, 20 mL, and 50 mL amber USP Type I vials for intramuscular or subcutaneous administration. The applicable compliance boundary includes Ph. Eur. 5.1.1 for methods of preparation of sterile products, Ph. Eur. 2.6.1 for sterility testing, Ph. Eur. 2.9.19 for sub-visible particulate matter, VICH GL18(R2) for residual solvent limits, and ICH Q3D for elemental impurities. The formulation is incompatible with strong alkalis, oxidising agents, and prolonged heat above 121°C; autoclave load validation is required when fill volume exceeds 50 mL due to extended core-temperature lag.

For poultry drinking-water lines, the stock solution is compounded as a hydroalcoholic system to prevent precipitation of Sophora alkaloid salts in hard water. The stock solution contains 3.0% v/v of the API, 8.0% v/v ethanol, and citric acid to maintain pH 3.8–4.2. At this pH, hydrolysis of oxymatrine is retarded, and the solution can be held for 72 h at 30°C with an acceptance criterion of ≥98% HPLC peak-area retention. The final drinking-water addition ratio is 0.5–1.0 L stock per 1,000 L of drinking water, giving a nominal API concentration of 150–300 mg/L. Production uses a low-shear compounding vessel with overhead impeller at 80 rpm, a 0.45 μm bag filter, and aseptic filling into 5 L and 20 L HDPE jerry cans. Terminal products are 5 L liquid concentrates and 20 L farm-pack solutions for proportional dosing pumps. Normative references include EU Directive 2001/82/EC as amended for veterinary medicinal products, Ph. Eur. 2.6.12 for microbiological examination of non-sterile products, ISO 6888-1:2021 for coagulase-positive staphylococci, and WHO Guidelines for Drinking-water Quality with respect to residual disinfectant compatibility. Published data for combination stability with chlorinated drinking water above 2 mg/L free chlorine is limited; water-medication formulators should run a 24-h spiked-water challenge before field use.

What Moisture Threshold Keeps Water-Soluble Granules Below Caking Risk?

Water-soluble granules for swine and poultry are produced by fluid-bed top-spray granulation because the extract tends to cake when residual moisture exceeds 3.0% w/w. The dry blend consists of 5.0–10.0% w/w API, 85.0–90.0% w/w glucose monohydrate, and 2.0–3.0% w/w povidone K30 dissolved in purified water. A 250 kg batch is blended in a double-cone blender at 12 rpm for 20 min before transfer to a fluid-bed unit. Granulation operates at inlet air temperature 55–65°C, outlet air 35–40°C, and spray rate 180–220 g/min. Final granules are sized through a 1.0 mm screen to give D50 350–500 μm and are dried to moisture ≤3.0% w/w. The in-use addition ratio is 1.0–2.0 g granules per 1 L of drinking water, producing a metered dose that can be administered through proportioners set at 1% stock dilution. Terminal product types are 100 g, 500 g, and 1 kg HDPE jars and 10 kg bulk bags. Normative references include Ph. Eur. 2.9.31 for particle-size analysis by laser diffraction, Ph. Eur. 2.9.40 for uniformity of dosage units, ISO 4833-1:2013 for aerobic plate count, and USP <795> as a reference for nonsterile compounding limits. The granule form should not be exposed to ambient relative humidity above 60% RH during packaging; unlined paper bags are not acceptable because alkaloid salts migrate and adhere to the surface.

Feed-Mill Premix Stability under High-Fat Extrusion

In feed-mill integration, the API is first diluted into a carrier premix at 10.0% w/w using wheat middlings or calcium carbonate as carrier. The premix is drawn into a 2,000 L ribbon mixer and mixed for 10 min at 20 rpm with a coefficient of variation target of ≤5% for total alkaloid assay. The final feed addition ratio is 1.0–2.0 kg of 10% premix per 1,000 kg of finished feed, equivalent to 100–200 g API per tonne. Because allicin-related markers degrade when exposed to pelleting temperatures above 85°C for more than 30 s, the preferred production process uses post-pellet liquid spray of a filtered hydroalcoholic dilution at 0.1–0.2% w/w of finished feed, applied through a twin-fluid nozzle on the cooler discharge belt. Terminal product types are 25 kg multi-wall paper sacks with inner polyethylene liner and 1,000 kg bulk bags. Compliance references include Regulation (EC) No 1831/2003 for feed additives, Regulation (EU) 2019/4 on medicated feed, ISO 6497:2002 for feed sampling, and FDA 21 CFR 558.4 where the API is classified as an animal drug for feed use. Cross-contamination control must be validated by sequencing this premix after bulk mineral carriers; published carry-over data for this specific botanical extract in high-fat feed lines is limited.

When Immersion Delivery Replaces Oral Dosing in Freshwater Aquaculture

In freshwater aquaculture, immersion treatment is used where oral intake cannot be verified or where the pond population exhibits reduced feeding. The API is pre-solubilised in 10% v/v ethanol and then diluted in a holding tank to 2–10 mg/L total matrine, with aeration maintained above 5.0 mg/L dissolved oxygen as measured by ISO 5814:2012 optical probe. The pH of the bath is held between 6.5 and 7.5; acid conditions below 6.0 precipitate the alkaloid fraction from solution. The contact period is 20–30 min, after which the tank water is flushed through activated carbon before discharge. The terminal product type is a water-soluble sachet of 2 g or 10 g pre-weighed granulate for direct pond-side weighing; the production process for the sachet is dry granulation followed by nitrogen-flushed foil-pouch packing to maintain alliin content above 90% of label for 18 months at 25°C. Normative references include WOAH Aquatic Animal Health Code for prudent use of antimicrobial agents in aquatic animals, ISO 5814:2012 for dissolved oxygen measurement, and ISO 5667-3:2018 for water sampling. Published data for the environmental fate of matrine in pond sediments is limited; regional environmental risk assessment is required before discharge approval.

Tablet and capsule intermediates for companion animals are formulated as non-food-producing-species dosage forms, which removes residue-depletion constraints applicable to meat and milk but increases the demand for palatability and dose uniformity. Tablets are prepared by dry granulation of the API with mannitol, croscarmellose sodium 3.0% w/w, and magnesium stearate 0.5% w/w; the final compression blend contains 50–100 mg standardised extract per 8 mm round flat-faced punch. Compression is run on a 12-station rotary press at 10–15 kN compression force to achieve hardness 50–80 N and disintegration below 15 min in 0.1 M hydrochloric acid. Capsules are filled with 100 mg API pre-mixed with lactose monohydrate at 1:1 w/w; the fill blend is dried to ≤4.0% w/w moisture and filled into hard gelatin capsules of size 3. Terminal products are 30-count, 60-count, and 100-count aluminium/PVC blister packs or HDPE bottles with silica gel desiccant. Compliance references include Ph. Eur. 2.9.1 for disintegration, USP <905> for uniformity of dosage units, VICH GL11 for stability testing of veterinary medicinal products, and Ph. Eur. 5.1.4 for the microbiological quality of non-sterile pharmaceutical preparations. The extract is hygroscopic; direct compression should stop when ambient relative humidity exceeds 60% RH, and the granulation must be sealed within 4 h of drying to avoid hardness drift.