In piglet starter feed, the Wuwei Jianpi Mixture veterinary-grade API is incorporated through a two-stage carrier dilution to avoid segregation caused by particle-size mismatch between the botanical extract powder and ground maize. The API is first blended with defatted rice bran at a ratio of 1.0 part API to 9.0 parts carrier (w/w) in a 250 L plow mixer with a chopper speed of 1,440 rpm for 6 minutes; the pre-blend is discharged through a conical screen fitted with a 425 µm mesh to break agglomerates. This pre-blend is then metered into the main feed stream at 5.0 kg per 1,000 kg finished ration, resulting in a final nominal API inclusion of 0.5 g/kg. Mixing is performed in a 1,000 L single-shaft ribbon mixer at 18 rpm for 12 minutes after addition of 2.0% soybean oil as a dust suppressant and binder. Homogeneity is verified by sampling at 10 points according to ISO 6497:2005 and analyzing the marker peak area by high-performance liquid chromatography at 270 nm; the relative standard deviation across all sampling points is required to remain below 5.0% for three consecutive production lots. Moisture in the finished feed is tested by ISO 6496:1999 at 103°C ± 2°C and is maintained below 4.5% to prevent mold growth. Microbial limits are checked by ISO 4833-1:2013 for total aerobic count and ISO 6579:2017 for Salmonella absence in 25 g. The terminal product can be delivered as a meal or formed into 3.0 mm pellets after conditioning at 68°C for 20 seconds, followed by cooling to 25°C; pellet durability index is evaluated by ASAE S269.5 only for pelleted presentations. The finished product is packaged in 25 kg multi-wall paper bags lined with polyethylene.

A 1:7.5:1.5 Dry Blend for Poultry Drinking Water Delivery

The water-soluble powder for poultry is prepared by dry blending the API with glucose monohydrate and anhydrous citric acid at a ratio of 1.0:7.5:1.5 by weight, respectively; the citric acid both adjusts pH and reduces microbial growth during the standing period in open drinker systems. The blend is passed through a stainless steel sieve of 200 µm (74 mesh) to remove coarse particles, because particles retained above 200 µm exceed 5.2% of total blend mass and settle visibly in 500 L stock tanks. Reconstitution at 1.0 g powder per liter is performed in a 500 L polyethylene tank with a 0.55 kW stainless steel paddle agitator operating at 140 rpm for 10 minutes. The resulting solution pH is maintained at 4.2–5.0; solution clarity is checked with a nephelometer and is rejected when turbidity exceeds 10 NTU, since excess turbidity clogs in-line medicator diaphragms and nipple drinker restrictors. Total aerobic plate count after 24 h at 25°C is determined by ISO 4833-1:2013 and must remain below 1.0×10⁴ CFU/mL, while Salmonella is tested by ISO 6579:2017 and must be absent in 25 mL. Dosing pump calibration is performed against a graduated cylinder at 0.5 L/min, 1.0 L/min, and 2.0 L/min; flow variation greater than 5.0% between settings triggers pump replacement before flock treatment. The terminal finished products are a 10 g/L in-use solution delivered through closed-loop drinking lines, or a pre-weighed water-soluble sachet for tiered dosing.

When the Extract Powder Is Added at 2.5 kg/t to a Ruminant Total Mixed Ration

When the Wuwei Jianpi Mixture API is added at 2.5 kg/t to a ruminant total mixed ration, the carry-in vehicle must compensate for the botanical powder’s high affinity for moisture and its tendency to attach to mixer walls. A practical operating sequence begins with the preparation of a 1:9 pre-blend of API in ground oat hulls or limestone carrier (<250 µm) using a double-ribbon mixer with L/D ratio 2.0:1 and jacket temperature 30°C. The pre-blend is then metered through a screw feeder at 250 kg per batch into 10,000 kg of TMR while the vertical two-auger mixer operates at 19 rpm; this corresponds to a final API level of 2.5 kg/t dry matter equivalent. Mixing continues for 20 minutes after the last pre-blend addition, and TMR samples are drawn from 12 points using the square-section probe specified in ISO 6497:2005. Moisture is measured by ISO 6496:1999 and held below 5.0%; the carrier’s moisture absorption is controlled by pre-drying at 45°C for 90 minutes if ambient relative humidity exceeds 60%. Heavy metal limits for the finished premix are verified by inductively coupled plasma mass spectrometry against the limits in GB 13078-2017 for lead, cadmium, arsenic, and mercury. The terminal finished product is either a meal TMR for beef cattle or a compacted 6 mm pellet for sheep; pellet quality is assessed by ASAE S269.5 with a minimum 95.0% durability for pelleting lines using a 3.0 m retention time in the conditioner.

What Prevents Terminal Sterilization of the Injectable Presentation Without Loss of Marker Recovery?

Sterile aqueous injections of the Wuwei Jianpi Mixture API are processed by aseptic filtration rather than terminal steam autoclaving because the polysaccharide-rich fraction forms a brown precipitate when held at 121°C for 15 min in a standard pass-through autoclave. The manufacturing sequence begins with dissolving the API in Water for Injection at 35°C ± 5°C at 20 g/L; pH adjustment to 5.8–6.5 is made with 0.1 M sodium hydroxide or 0.1 M hydrochloric acid, and the solution is stirred for 30 minutes in a jacketed glass-lined vessel. Clarification is performed through a 0.45 µm polyethersulfone membrane followed by a 0.22 µm PVDF final filter; filter integrity is evaluated by bubble point testing according to the filter manufacturer’s protocol before and after the batch. The filtrate is filled into 10 mL amber Type I glass vials under ISO 14644-1 Class 5 laminar airflow with an aseptic filling line operating at 60 vials/min. Endotoxin is analyzed by gel clot limulus amebocyte lysate assay aligned to USP <85>; the release limit is set at <0.25 EU/mL for this parenteral preparation. Sterility is tested according to USP <71> by membrane filtration using fluid thioglycollate medium and soybean-casein digest medium. The terminal product is a 10 mL single-dose injection containing 20 g API per 1,000 mL, corresponding to 200 mg API per 10 mL vial; the vial is nitrogen-flushed to a headspace oxygen content below 1.0% and sealed with a 20 mm bromobutyl rubber stopper and aluminum flip-off cap.

Wet Granulation Endpoint and Tablet Ejection in Calf Oral Boluses

Tablets are produced by wet granulation because the API has a Carr index above 25 and an angle of repose above 40°, making direct compression on a rotary press unworkable. The dry blend contains 30.0% API, 55.0% microcrystalline cellulose, 10.0% sodium starch glycolate, and 5.0% povidone K30; binder solution is 12.5% w/w povidone K30 in 50% ethanol and is added at 15% of the dry powder mass. Granulation endpoint is reached when a sample pressed by hand breaks cleanly without releasing free powder and the wet mass passes through a 12-mesh screen without extruding into strings. The granules are dried in a fluid-bed dryer at 45°C until loss on drying is ≤4.0%, measured by ChP General Chapter 0831. After drying, granules are sized through a 20-mesh screen and lubricated with 0.5% magnesium stearate and 1.0% crospovidone for 5 minutes in a V-blender. Tablets are compressed on a 16-station rotary press using 12 mm round flat-faced beveled tooling at 15 kN compression force; average hardness is 80–100 N measured by a Schleuniger hardness tester, and friability remains below 1.0% according to USP <1216>. Disintegration time in water at 37°C is ≤15 min by ChP 0921. The terminal finished product is a 1,500 mg calf oral bolus containing 450 mg API per bolus, packaged in aluminum-PVC blister packs to limit moisture ingress.

For hard capsule filling, the Wuwei Jianpi Mixture API is pre-dried at 40°C under 0.08 MPa vacuum for 90 minutes and then dry-blended with microcrystalline cellulose and colloidal silicon dioxide at a ratio of 1.0:1.0:0.02 by weight. The pre-dried blend is filled into size 1 hard gelatin capsules at a target fill weight of 505 mg per capsule, equivalent to 250 mg API, 250 mg microcrystalline cellulose, and 5 mg colloidal silicon dioxide; a Zanasi LZ-64 intermittent-motion capsule filler with 12,000 capsules/h operating speed is used. Weight uniformity is measured by gravimetric analysis of 20 capsules according to USP <905>; acceptance requires not more than 2 capsules outside ±10% of average fill weight and none outside ±20%. Moisture uptake after 24 h at 40°C/75% RH is monitored by an MB120 moisture analyzer and controlled below 6.0%; packaging therefore consists of 60 mL HDPE bottles with a desiccant canister and an induction-sealed liner. The terminal product is a botanical hard capsule for oral administration; disintegration is checked by ChP 0921 and must be ≤20 min in 900 mL water at 37°C.

Can Extrusion-Spheronization Improve Granule Uniformity in Top Dressing Applications?

Extrusion-spheronization is selected for top dressing granules because it yields a narrow particle-size fraction that resists segregation and dust formation during hand mixing into feed. The granulation charge is composed of 25.0% API, 65.0% microcrystalline cellulose, and 10.0% lactose monohydrate; purified water is added at 35% of dry mass in a planetary mixer until a stiff dough forms. The wet mass is extruded through a dome extruder equipped with a 0.8 mm screen at 45 rpm, then spheronized at 900 rpm for 4 min on a 0.4 mm cross-hatch friction plate. Spheroids are dried at 45°C in a fluid-bed dryer to a loss on drying ≤4.0%, then classified by sieve analysis using a vibratory sieve shaker; the target fraction is 500–850 µm and must account for ≥90% of the batch. Bulk density is measured by a Scott volumeter according to USP <616> Method I; the target bulk density is 0.55–0.65 g/mL, and tapped density gives a Hausner ratio between 1.15 and 1.25. Marker compound recovery is determined by HPLC at 270 nm after accelerated storage at 40°C/75% RH for 30 days; recovery below 95.0% relative to initial is grounds for reformulation with reduced lactose. The terminal product is a top dressing granule for calves or lambs packed in 2 kg laminated foil pouches.

For ready-to-use oral solutions, the Wuwei Jianpi Mixture API is dissolved in a mixed solvent system consisting of purified water 50.0%, sorbitol 70% solution 40.0%, and propylene glycol 10.0% by volume, with potassium sorbate 0.1% w/v as a preservative. The batch is heated to 60°C for 15 minutes in a jacketed stainless tank under a propeller agitator at 120 rpm to reduce viscosity and accelerate dissolution; the solution is then cooled to 25°C and filtered through a 50 µm polypropylene bag filter. The target concentration is 20.0 g API per liter, yielding 100 mg API per 5 mL dose; pH is adjusted to 4.5–5.5 with citric acid before final filtration. Clarity is checked visually and with a nephelometer, with acceptance at ≤15 NTU; sediments are quantified after 72 h at 25°C by a centrifugation method at 3,000 rpm for 10 minutes, where sediment volume ≤0.5% of total volume is required. The solution is filled into 1 L high-density polyethylene bottles under normal ambient conditions, using a peristaltic pump calibrated to ±1.0% fill volume. Microbial enumeration is performed by ISO 4833-1:2013; total aerobic count must remain below 1.0×10³ CFU/mL after 30 days at 25°C. The terminal finished product is a ready-to-use oral solution for calves and small ruminants.