Shiliu granules veterinary grade API is a granulated extract prepared from the dried pericarp of Punica granatum L. and standardized to a declared ellagitannin profile intended for use in veterinary dosage forms. The article is supplied as a free-flowing granulate that supports dry blending, wet granulation, capsule filling, oral powder sachets, feed premix dilution, drinking water reconstitution, and, under restricted conditions, sterile solution development. Values cited in the following application-specific sections are formulation starting points that must be verified against the supplier certificate of analysis and the target-market registration file; published data for certain species-specific configurations is limited.

In swine oral enteric powders and medicated feed premixes, the granulated pomegranate-rind extract is used as an astringent, non-antibiotic adjunct in veterinary-supervised programs. The inclusion rate in final feed is 0.8–2.5 kg/t when the granulated article is standardized to 20% total ellagitannins; manufacturers adjusting to a crude pomegranate rind equivalent of 3–10 g per finishing pig per day should recalculate against the certificate of analysis for each batch because ellagitannin content has been observed to vary from 18% to 24% in production-scale lots. Compliance for a medicated premix follows 21 CFR 225 and 21 CFR 226 in the United States, while EU markets require classification under Regulation (EU) 2019/6 if the finished product carries a therapeutic claim. A feed additive route under Regulation (EC) No 1831/2003 applies only where the target jurisdiction has approved the extract for zootechnical or sensory use; such approval must be checked against the Union Register of Feed Additives and not assumed. Heavy metals are controlled against Ph. Eur. 2.4.8 and residual solvents against VICH GL18 in the API release specification.

The downstream production sequence for swine premixes typically uses a stainless steel ploughshare mixer with a 500 L working volume. The API is pre-dried in a vacuum shelf dryer at 45 °C until loss on drying by USP〈731〉 is ≤6.0%, then screened through an 80 mesh stainless steel sieve and pre-blended with 0.5% fumed silica to suppress hygroscopic caking. Mixing is performed in two stages: a 12-minute high-shear dispersion at 120 rpm, followed by a 6-minute low-shear V-blender homogenization with sampling at the upper, middle, and lower zones of the blender. A content uniformity acceptance criterion of RSD ≤5.0% is applied per 21 CFR 211.110. Terminal products include 100 g oral powder sachets for in-feed top dressing, 1 kg and 5 kg premix pouches, and 20 kg bulk treated feed bags. Equipment contact surfaces should be 316L stainless steel because ferric-ion interaction darkens ellagitannins; uncoated iron or copper must be avoided.

What pH and Water Hardness Limits Govern Poultry Drinking Water Formulations?

The water-soluble powder route is used for broiler and layer enteric programs; however, soluble ellagitannins are sensitive to pH and oxidative chlorine. The finished drinking water is typically diluted to 0.5–1.0 g/L for a granulated API standardized to 20% total tannins, but the exact final concentration must be derived from the registered product dose and the expected daily water intake of the flock. A stock solution is prepared in deionized water at 25 °C in a 50 L stainless steel vessel with an eductor funnel, then dispersed with a high-shear rotor-stator mixer at 3,000 rpm for 15 minutes. The vehicle is acidified with citric acid to pH 4.0–5.5; above pH 7.5, the phenolic hydroxyl groups oxidize and precipitate as dark floc. Hard water with total hardness above 250 mg/L CaCO₃ requires 0.2–0.5% sodium hexametaphosphate as a sequestrant before API addition. Chlorinated municipal water should be dechlorinated by activated carbon or sodium thiosulfate at 0.01% because free chlorine accelerates color change and assay loss. The final solution is filtered through a 100 µm inline screen, held at 4–8 °C, and used within 8 hours to limit microbial proliferation. Terminal products are 100 g sachets of water-soluble powder, 500 g jars for large flocks, and 5 L stock solution containers for proportioning pumps. The nonsterile aqueous solution is released under USP〈1231〉 water quality guidance and USP〈2021〉 microbial enumeration; EU production sites follow Regulation (EU) 2019/6 and WHO GMP for veterinary medicinal products.

Ruminant Tablet Compression Variables and Rumen-Drench Suspension Stability

For ruminant tablets and boluses, the granulated API is incorporated at 10–30% w/w of the tablet core for 1 g and 3 g veterinary tablets. Direct compression of the neat API is generally not recommended because the dry extract exhibits high cohesiveness and variable flow; dry granulation by slugging at 5–10 kN followed by milling through a 1.0 mm ConiWitt sieve produces a free-flowing granulate suitable for rotary compression. The compression blend contains dicalcium phosphate dihydrate as filler, croscarmellose sodium at 2.0% as disintegrant, and magnesium stearate at 0.5% added externally. A 10-station rotary tablet press operating at 16 kN compression force typically yields tablets with friability ≤0.8% under USP〈1216〉 and disintegration time ≤15 minutes in 0.1 N HCl under USP〈2040〉. Uniformity is confirmed by USP〈905〉 with acceptance value ≤15.0.

Rumen drench suspensions require a separate production line because the extract interacts with alkaline buffers and iron-containing minerals. The liquid vehicle is prepared with xanthan gum at 0.25%, citric acid to pH 5.0, potassium sorbate at 0.1%, and purified water; the granulated API is then dispersed under high shear and passed through a 150 µm inline filter to remove undissolved botanical fines. Terminal products include 1 g tablets, 3 g boluses, and 500 mL rumen drench bottles. The oral liquid must not be combined with sodium bicarbonate buffer in the same drench because the resulting pH shift causes ellagitannin-protein precipitation and clogging of balling-gun nozzles. Regulatory release for both tablets and oral liquids follows 21 CFR 210 and 21 CFR 211 for animal drugs in the United States, Regulation (EU) 2019/6 in Europe, and VICH GL18 for residual solvent control in the finished product.

Hard gelatin capsule filling with the granulated API is relatively straightforward when the granulation is dry and free-flowing, but it must not be treated as a universal direct-fill operation because triboelectric charging at low moisture creates weight variation. In a dosator-type capsule machine, the granulated API is dry granulated by slugging at 5–10 kN, sieved through a 1.0 mm ConiWitt sieve, and filled into #3 or #0 hard capsules at 25–45% w/w with lactose monohydrate and 0.5% magnesium stearate. The terminal products are 250 mg and 500 mg veterinary capsules for companion animals, released under USP〈905〉 and USP〈2040〉. Regulatory compliance follows 21 CFR 210 and 21 CFR 211 for animal drugs; if marketed as a non-drug supplement, 21 CFR 507 applies instead. A narrow moisture window of 2.0–5.0% is required because above 5.0% the granulate smears on capsule bushings, while below 2.0% static electricity reduces fill weight consistency.

When Sterile Injectable Solutions Are Required from a Tannin-Bearing Veterinary API

Aqueous injectable presentation is the most process-critical route and should not be attempted with the crude granulated API unless the fraction has been purified to remove high-molecular-weight protein-binding polyphenols and endotoxin. The conditional starting concentration is 1–5% w/v of the purified ellagitannin fraction; the exact injection strength must be supported by compatibility and pharmacological data, and published data for this specific configuration is limited. The formulation vehicle uses Water for Injections with pH adjusted to 5.0–6.0 with acetate buffer because higher pH causes precipitation and lower pH can degrade glycosidic linkages. A 0.1% sodium metabisulfite anti-oxidant may be added, but only after confirming compatibility with container closures.

Processing is aseptic: the solution is prefiltered through a 0.45 µm PVDF membrane, then sterilized by 0.22 µm sterilizing-grade filtration under nitrogen pressure ≤2 bar. Terminal steam sterilization is typically not used because moist heat above 60 °C accelerates ellagitannin oxidation and color shift. Filling is conducted in a Grade A laminar flow unit over Grade B background, and the acceptance criteria for sterility and endotoxin follow USP〈71〉 and USP〈85〉, with a target endotoxin level below 0.5 EU/mg. Terminal products are 10 mL and 50 mL vials; multi-dose vials require an antimicrobial preservative validated by USP〈51〉. This route is not appropriate for crude API due to protein-binding and particulate risk. If terminal sterilization is required by the market, ISO 17665 steam sterilization validation would apply, but the heat sensitivity of the tannin fraction makes aseptic filtration the primary development option.

Horse Oral Paste Rheology Depends on Granulated API Particle Size and Moisture Budget

In equine oral paste formulations, the API is dispersed at 5–20% w/w in a thixotropic base typically composed of 0.5% carbomer, 5% glycerin, and a buffered aqueous phase adjusted to pH 5.0–5.5. The granulated API is first milled through a 0.5 mm screen and pre-dried to ≤5.0% moisture before being incorporated into a high-torque planetary mixer; vacuum deaeration is applied at -0.8 bar for 20 minutes to eliminate air bubbles that cause rheology instability during syringe filling. Particle size influences mouthfeel and syringeability: a D90 above 180 µm produces gritty texture, while a D90 below 50 µm increases yield stress beyond the target range of 800–1,200 Pa·s at shear rate 10 s⁻¹. Terminal products include 30 mL dial-a-dose oral paste syringes, 400 g free-choice granulate buckets, and 50 g single-dose powder pouches. Compliance for equine non-food products requires adherence to 21 CFR 507 if classified as animal food, or 21 CFR 210 and 21 CFR 211 if registered as an animal drug; for performance horses, the finished product should be screened against the FEI Equine Prohibited Substances List for contaminants introduced during raw material handling.