Yupingfeng Granules Veterinary Grade API is a standardised ternary botanical extract granulate prepared from Astragalus membranaceus var. mongholicus root, Atractylodes macrocephala rhizome, and Saposhnikovia divaricata root in the traditional dry-weight ratio of 3:1:1. The material is extracted with 60–70% v/v ethanol-water, clarified by disc-stack centrifugation at 8,000–10,000 rpm, concentrated under vacuum at 55–65°C, and spray-dried with a maltodextrin or soluble starch carrier. The resulting granulate is light yellow-brown to brown, hygroscopic, water-dispersible, and intended for further manufacture into tablets, capsules, oral powders, granules, premixes, oral solutions, and—after additional purification—injectable solutions for veterinary species.

No harmonised international monograph assigns a single model number to this material. Commercial designations are customarily tied to marker content and sieve fraction; representative suffixes are YPF-VET-API-G for granular direct-compression grade, YPF-VET-API-F for fine-milled premix grade, and YPF-VET-API-I for clarified low-endotoxin injectable intermediate. At production scale, spray-dried lots are typically dried on a rotary atomizer dryer with inlet air temperature 170–190°C and outlet air 80–90°C; feed solids are maintained at 25–35% w/v to prevent nozzle blockage and uncontrolled agglomeration. Because the carbohydrate carrier is hygroscopic, material exposed to ambient RH >60% for more than 20 min absorbs moisture and loses flowability. Pre-drying at 50°C for 2 h in a vacuum tray dryer is therefore specified before tablet compression or capsule filling in humid manufacturing facilities. On actual blending lines, a 3-minute high-shear mix at 120 rpm is sufficient for 1% w/w magnesium stearate lubrication, but longer mixing increases granule attrition and fines below 75 µm, causing segregation in hoppers.

Which Marker Compounds Define the Pharmacopoeial Identity of This API?

Marker compounds are used as release criteria because the pharmacopoeial identity of the three-component formula cannot be confirmed by a single chromatographic peak. The primary markers are astragaloside IV, calycosin-7-O-β-D-glucoside, atractylenolide I, and prim-O-glucosylcimifugin. A representative 5:1 granulate sets astragaloside IV at NLT 0.20% w/w by HPLC-ELSD, calycosin-7-O-β-D-glucoside at NLT 0.10% w/w, atractylenolide I at NLT 0.05% w/w, and prim-O-glucosylcimifugin at NLT 0.10% w/w. The four-marker acceptance window is established in the veterinary product dossier and may be tightened to ±10% of the target for injectable-grade material. Quantification is performed on a C18 column (250 mm × 4.6 mm, 5 µm) with a binary gradient of acetonitrile and 0.1% phosphoric acid; astragaloside IV is detected by evaporative light scattering because of weak UV absorption. Identity is also supported by thin-layer chromatography against reference botanical extracts, consistent with the Chinese Veterinary Pharmacopoeia reference for Yupingfeng San. Atractylenolide I is frequently the most variable marker in raw-root lots; roots harvested before the third year may fall below the 0.05% w/w threshold, requiring pre-extraction pooling of botanical raw material before extraction.

Lot-to-lot control therefore depends heavily on raw-material sourcing. Astragalus root from 2–3-year cultivation cycles shows higher astragaloside IV content than younger roots, while Saposhnikovia root marker content varies with harvest region and post-harvest drying. The extraction process should use 60–70% v/v ethanol rather than absolute ethanol because atractylenolide I extraction efficiency drops sharply below 55% v/v ethanol and above 80% v/v ethanol. Concentration must be performed below 65°C to limit degradation of prim-O-glucosylcimifugin; vacuum belt dryers or wiped-film evaporators are preferred over open-pan evaporation. The standardised extract is then blended with a carrier to a target marker content before spray drying, so that variation in the native extract is corrected before final powder handling.

Granular Flow, Sieve Cut, and Residual Solvent Specifications

Particle-size distribution is controlled by laser diffraction according to ISO 13320:2020 and analytical sieving according to USP <786>. For direct-compression grade, the target is D10 ≥ 45 µm, D50 120–180 µm, and D90 ≤ 300 µm; for premix grade, a finer fraction with D90 ≤ 150 µm reduces segregation in multi-component feed premixes. Bulk density and tapped density are measured according to USP <616>; typical bulk density is 0.45–0.60 g/mL, tapped density 0.60–0.75 g/mL, and Hausner ratio 1.25–1.35. Moisture content determined by loss on drying at 105°C according to USP <731> is NMT 5.0% w/w. Extractable water-soluble polysaccharide content, expressed as glucose equivalents after acid hydrolysis, is 15–25% w/w and is monitored because it influences granule dissolution and solution viscosity.

Residual solvent compliance follows ICH Q3C: ethanol is Class 3 with a limit of 5000 ppm. If methanol or ethyl acetate are used during extraction or column purification, they must also be monitored at Class 3 limits. The elemental impurity values shown above align with the oral route limitations in USP <232>; injectable-grade material requires lower cadmium and mercury limits and should be evaluated against the parenteral route table. Pesticide residues are assessed according to USP <561> or European Pharmacopoeia 2.8.13, and aflatoxin B1 is typically controlled at ≤ 2 µg/kg in botanical material for oral use. The granulate is packed in double-layer polyethylene/aluminium foil bags with desiccant and stored at ≤ 25°C and ≤ 60% RH; shelf life is assigned only after long-term and accelerated stability studies on the specific finished dosage form.

When Injectable Solutions Are Prepared from Whole Granules, Which Process Steps Must Be Redesigned?

Direct reconstitution of the granular API in Water for Injection yields a turbid dispersion, not a clear solution, because the maltodextrin carrier and insoluble cell-wall fragments remain. Injectable dosage development therefore requires a dedicated clarified extract or additional separation: dissolution at 50°C, centrifugation at 15,000 × g for 20 min, filtration through 0.45 µm followed by 0.22 µm polyethersulfone membrane, and subsequent lyophilisation or aseptic filling. The carrier is removed or replaced with mannitol or trehalose before terminal sterilisation. The use of standard granular grade in injectable processing is not recommended without this treatment because the starch-based carrier contributes particulate matter and increases the risk of pyrogen load.

Bacterial endotoxin control becomes critical because raw botanical mass may contain high endotoxin burden. The parenteral-grade API must be tested by USP <85>; the final endotoxin limit is dose-dependent, commonly set at ≤ 0.5 EU/mg for veterinary injectable products. Steam sterilisation at 121°C for 15 min may reduce atractylenolide I content through oxidative degradation; published kinetic data for this specific multi-component formulation is limited, so terminal sterilisation should be validated by marker recovery rather than assumed. Avoid amine-based buffers or amino acid solutions because the reducing sugar terminals in maltodextrin can undergo Maillard reactions at pH >7.0 and elevated temperature. Citrate or phosphate buffers at pH 5.0–6.5 are preferred. Sodium metabisulfite is compatible at 0.1% w/w but must be evaluated for colour shift; ascorbic acid lowers pH and may precipitate polysaccharides. pH values below 3.5 cause visible precipitation in aqueous oral and injectable solutions, and high-salt parenteral vehicles above 0.9% w/v sodium chloride can reduce polysaccharide solubility.

Unlike single-marker astragalus extracts, this ternary API requires simultaneous quantification of multiple markers, leading to a higher analytical burden and narrower batch release windows. Compared with levamisole HCl, Yupingfeng Granules Veterinary Grade API is a multi-component botanical product with no single molecular entity; pharmacokinetic bioequivalence cannot be expressed by the AUC of one analyte. Compared with crude Yupingfeng powder, the API has controlled moisture and microbial load and is suitable for direct compression, whereas crude powder may require irradiation or steam treatment, both of which can alter marker profile. Published data on marker recovery after gamma irradiation at 10 kGy for this specific formula remain limited, so irradiation is not a default recommendation. Compared with single-herb Astragalus polysaccharide powders, the ternary API contains triterpenoid saponins and coumarin-type markers that broaden the analytical release profile but complicate forced degradation studies. Compared with yeast beta-glucan immunomodulators, the API contains multiple water-soluble polysaccharide fractions and small-molecule markers; its solution viscosity rises with concentration and is pH-dependent, while beta-glucan dispersions typically exhibit higher gelation tendency.

Dosage-Form Compatibility Is Not Uniform Across Compression and Solvent Conditions

Compression and solution processing place different demands on the API. For tablets, direct compression is preferred over wet granulation because the hygroscopic granulate can form hard agglomerates and reduce marker homogeneity. Main compression force of 10–20 kN on a rotary tablet press is used to achieve tablet hardness 60–80 N; the formulation should include microcrystalline cellulose and croscarmellose sodium, while magnesium stearate should be limited to 0.5–1.0% w/w to avoid delaying disintegration. Tablet friability is controlled according to USP <1216>, disintegration according to USP <701>, and dissolution according to USP <711> using marker release rather than single-entity UV absorption.

For capsules, the powder bed moisture should be maintained at or below 4.5% w/w before filling; filling at 40–50% RH prevents hygroscopic clumping in the dosator. Premix manufacturing requires the API to be blended with feed-grade carrier such as calcium carbonate or precipitated silica to prevent segregation; a ribbon mixer run at 15 rpm for 5 min is typically sufficient for 1–3 kg/tonne inclusion, but recovery must be confirmed by marker HPLC analysis of the finished premix. Oral solutions are filled by volume after hydration and pH adjustment; sedimentation after 72 h at 40°C and 75% RH should be ≤ 1% by volume when the formula is stored upright. The injectable form requires the tightest controls because the raw botanical granulate is not inherently sterile or pyrogen-free; final sterility is tested by membrane filtration according to USP <71> after aseptic processing or terminal sterilisation.

Safety and regulatory status must be established in the final marketing authorisation. The material is for veterinary use only and is not a single chemical entity. Compliance is established against the Chinese Veterinary Pharmacopoeia reference for Yupingfeng San where applicable; elemental impurities follow USP <232>; residual solvents follow USP <467> and ICH Q3C; microbiological quality follows USP <61>, USP <62>, or European Pharmacopoeia 5.1.4 for herbal products for oral use. In food-producing animals, withdrawal periods must be established from tissue depletion studies of the marker compounds or their metabolites, not assumed from the absence of synthetic residues. The API should not be combined with strong oxidising agents because polyphenols and saponins may degrade, and combinations with high-pH amine-based additives are contraindicated for the reasons described in injectable processing.