In breeding-herd feed programmes targeting post-partum urinary function in sows, Rubi Fructus spray-dried extract with a release specification of ≥2.0% ellagic acid by HPLC and ≤6.0% moisture is proportioned at 1.2–2.5 kg per metric tonne of finished lactation and gestation feed. The active is conveyed into a 20 kg intermediate premix of ground rice hulls and calcium carbonate, and this intermediate is then diluted into a 1000-L horizontal ribbon blender at 25 kg per tonne of final premix, a 2.5% w/w incorporation. Batching on a 1200-L trough mixer with a ribbon tip speed of 1.5–2.0 m/s and a fill level of 60–70% requires 8–12 min mixing after final addition; subsequent sampling at 8 positions yields ellagic acid coefficient of variation ≤5.0%. Pre-sieving the spray-dried extract through 40 mesh mitigates cone segregation observed on production lines where the active has a bulk density of 0.28–0.35 g/mL and a Hausner ratio 1.35–1.55. The premix is discharged into moisture-barrier liners with ambient relative humidity controlled to ≤60%; at higher relative humidity, the extract flow function coefficient drops from ff 7.2 to ff 4.0 on a Jenike shear cell, increasing bridging in hopper screw feeders. Compliance is maintained under GMP+ BA2, FAMI-QS Version 6.0, and ISO 22000:2018; the botanical raw material is identified against the Rubi Fructus monograph of the Chinese Veterinary Pharmacopoeia (2020) with heavy metal limits per ISO 17025-accredited methods. Terminal product types include 0.5% and 1.0% sow premixes, pelleted lactation feeds steam-conditioned at 70–80°C through a ring die, and mash concentrates for on-farm dosing.

What Limits the Reconstitution Time of Rubi Fructus Water-Soluble Granules in High-Carbonate Drinking Water?

Reconstitution of Rubi Fructus water-soluble granules in broiler and layer houses is strongly reduced when soluble calcium and magnesium carbonates exceed 200 mg/L total hardness, because catechol-bearing polyphenols in the extract form insoluble metal complexes above pH 7.0. The granulation formulation therefore includes buffered citric acid to hold the made-up stock solution at pH 5.0–5.5; the addition ratio of spray-dried Rubi Fructus extract is 35–45% w/w, with maltodextrin DE 12–15 at 45–55%, citric acid anhydrous at 3–5%, and colloidal silica at 1.0%. In a top-spray fluid-bed granulator, a 120 kg batch is sprayed with water at 80–120 g/min, inlet air 55–60°C, product bed 35–42°C, and exhaust humidity ≤28%; dried granules are passed over a 0.8 mm sieve and a 0.25 mm retention sieve. The resulting granulate shows a bulk density of 0.60–0.70 g/mL and a Carr index ≤15. Reconstitution bench testing with water at 25°C in a 1000 mg/L stock solution achieves ≥95% transmittance after 5 min when pH is kept below 5.5; at pH 7.8, insoluble residue on a 0.45 µm filter exceeds 8% of initial mass. Compliance of the granules as a veterinary premix/feed additive is governed by FAMI-QS Version 6.0, ISO 22000:2018, and VICH GL18(R2) for residual solvents from the extract; the Rubi Fructus marker is quantified by HPLC with a specification of ≥2.0% ellagic acid in the extracted solid. Terminal product types include 100 g and 250 g polyethylene jars, 1 kg multilayer pouches, and stock solution concentrates for proportioner pumps set at 1:1000 delivery into nipple lines.

Companion Animal Capsule and Tablet Compression with 10:1 Native Extract

For companion animal veterinary formulations targeting urinary function, Rubi Fructus 10:1 native extract is incorporated into direct-compression and dry-granulation lines at 15–25% w/w of the core matrix. The extract presents caking and poor flow because it is hygroscopic at relative humidity ≥60% and has a compact angle of repose of 38–44°; roller compaction is therefore preferred over direct compression. In a 200 kg batch, the extract is pre-blended with microcrystalline cellulose PH-102 at 55–65%, croscarmellose sodium 2.0%, colloidal silicon dioxide 1.0%, and mannitol as bulking agent. Roller compaction is run at a gap of 1.2–1.8 mm and a hydraulic pressure of 40–60 bar; the ribbons are milled to granules with ≥80% between 0.5–2.0 mm. Final lubrication with magnesium stearate at 0.5–1.0% for 3–5 min in a 100-L V-blender prevents over-mixing that would slow disintegration. Tableting on a 16-station rotary press at 30–60 rpm with a compression force of 8–14 kN produces caplet cores with hardness 5–8 kp; USP 701 disintegration of the coated tablet remains ≤30 min in 0.1 N HCl. Capsule filling with the same granulate on a dosator machine at 12,000–20,000 units/h uses Size 2 or 3 hard gelatin/HPMC capsules. Compliance for marketed products follows FDA 21 CFR Part 210/211 when the item is registered as an animal drug, and the NASC quality program when sold as a companion animal supplement; the Rubi Fructus extract must conform to the Chinese Veterinary Pharmacopoeia monograph for foreign matter and heavy metals. Terminal dosage units include 100 mg and 200 mg coated tablets and capsules with a label claim of extract 50–100 mg per unit. Storage incompatibility is documented with ascorbic acid above 2%, which accelerates polyphenol color shift from tan to deep brown within 30 days at 40°C/75% RH.

When Rubi Fructus Clarified Polysaccharide Fraction Is Processed by Aseptic Filtration for Parenteral Administration

Aseptic processing of a clarified Rubi Fructus polysaccharide fraction for injectable dosage forms is carried out only where the extract has a documented bacterial endotoxin load below 0.5 EU/mg and a residual ethanol limit below 5000 ppm under VICH GL18(R2). The formulation ratio is 10–20 mg/mL of the clarified fraction in water for injection, with pH adjustment to 6.0–6.5 using dilute sodium hydroxide after the solution is chilled to 4°C for 24 h to flocculate low-solubility tannins. The solution is clarified by depth filtration with a 0.45 µm cellulose/polypropylene plate and then sterile-filtered through a 0.22 µm polyethersulfone membrane in a filling suite meeting ISO 14644-1:2015 Class 5; total particulate matter is checked per USP 788 in the final containers. Terminal sterilisation at 121°C for 15 min is avoided unless forced-hydrolysis studies show ellagic acid recovery ≥90%; otherwise the process is restricted to aseptic filtration. Final product compliance requires USP 71 sterility and USP 85 bacterial endotoxin release with a limit of ≤0.25 EU/mL for large-animal intravenous preparations. The dosed solution is filled into 10 mL and 50 mL Type I glass vials with nitrogen overlay, and the terminal product types are veterinary parenteral solutions for cattle and equine clinical use. Published data for the specific Rubi Fructus polysaccharide parenteral configuration are limited in Western pharmacopoeial databases; therefore each lot requires loss-on-drying, biomarker, and container-closure integrity testing before release.

Following extraction in 60% aqueous ethanol at a plant material-to-solvent ratio of 1:8, the concentration step reduces the Rubi Fructus liquid to a dark-brown viscous syrupy material with total solids 55–65%; this concentrate is used at 10–20% w/w in a high-shear oral drench vehicle for adult ruminants. The vehicle consists of propylene glycol 20%, polysorbate 80 2.0%, potassium sorbate 0.1%, simethicone emulsion 0.2%, and purified water to 100%, with pH adjusted to 4.5–5.0 using citric acid. Mixing is performed in a 500 L in-line rotor-stator homogeniser at 500 rpm for 20 min at 20–30°C; the batch is then passed through a 100 µm in-line stainless steel strainer before filling. The dose rate is 10–15 g of native extract equivalent per animal per day, delivered as 50–100 mL of oral drench per head for adult cattle. Compliance is governed by ISO 22000:2018, GMP+ B1, and VICH GL18(R2) for extraction solvent residues; identity verification and marker quantification follow the Chinese Veterinary Pharmacopoeia Rubi Fructus monograph with ellagic acid specified at ≥2.0% in the concentrate. Filling into 1 L and 5 L high-density polyethylene or aluminium-laminated bottles is conducted under nitrogen flush; sediment formation below 5°C is a documented physical instability, and the product is warmed to 20°C with recirculation for 15 min before use. Terminal product types include oral drenches, liquid premixes for automatic drinking water proportioners at 1:500 dilution, and dosing pump concentrates.