| HS Code | 953397 |
| Product Name | Gamithromycin Veterinary Grade API |
| Api Grade | Veterinary Grade |
| Chemical Class | Macrolide Antibiotic |
| Cas Registry Number | 145435-72-9 |
| Empirical Formula | C40H76N2O10 |
| Appearance | White to almost white crystalline powder |
| Solubility | Freely soluble in methanol, ethanol, acetone, and dimethyl sulfoxide; practically insoluble in water |
| Storage Conditions | Store in a tightly sealed container protected from light, moisture, and heat at 15 to 30 degrees Celsius |
| Shelf Life | 24 to 36 months under recommended storage conditions |
| Veterinary Indication | Treatment and metaphylaxis of bacterial respiratory disease in cattle and swine |
| Target Species | Cattle, swine, and other veterinary species as prescribed |
| Available Dosage Forms | Tablets, Injections, Capsules, Powders, Granules, Premix, Solutions |
| Mechanism Of Action | Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit |
As an accredited Gamithromycin Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Packaged in sealed double polythene bags inside fiber drums, 25 kg per drum, for safe veterinary API handling. |
| Container Loading (20′ FCL) | Container Loading (20′ FCL): Gamithromycin veterinary grade API packed in sealed, palletized drums, secured and ventilated for safe maritime transport. |
| Shipping | Gamithromycin Veterinary Grade API is shipped in sealed, moisture-resistant containers with tamper-evident labels and accompanying SDS documentation. Transport requires dry, temperature-controlled conditions, protected from direct sunlight and extreme heat. Standard freight or express courier options are available, with secure packaging to ensure product integrity during transit for downstream formulation. |
| Storage | Store Gamithromycin Veterinary Grade API in a tightly sealed, light-resistant container in a cool, dry, well-ventilated area. Maintain temperatures between 15–30°C and protect from moisture, direct sunlight, and excessive humidity. Keep away from incompatible substances, heat sources, and open flames. Ensure proper labeling and secure access. Use original packaging until processing. |
| Shelf Life | Shelf life: 24 months in sealed original packaging under dry, cool, dark conditions; avoid heat, moisture, and sunlight. |
The conversion of gamithromycin veterinary grade API into a sterile injectable solution at production scale typically begins with dissolution of the free base in a non-aqueous or mixed aqueous-organic vehicle. Incoming API is released only when assay by HPLC is 98.0–102.0% on the anhydrous basis, total related substances do not exceed 1.0%, and residual solvents comply with VICH GL18 for the manufacturing route. The innovator injectable is reported as a clear solution with a nominal concentration of 150 mg/mL, equivalent to 15.0% w/v; public assessment documents list benzyl alcohol at 2% v/v as antimicrobial preservative for multi-dose packaging, with pH adjustment to the acidic range to maintain protonation of the tertiary amine group. Free-base macrolide solubility in water is below 0.1 mg/mL at pH 7.0; protonation below pH 5.5 increases aqueous solubility, but the exact buffering system is product-specific. The dissolved batch is chilled to 8–15°C to suppress oxidative hydrolysis before filtration, because the 15-membered lactone ring undergoes pH- and temperature-dependent hydrolysis at higher processing temperatures. The solution is inerted with nitrogen; residual oxygen in the headspace should not exceed 2% v/v where oxidation-sensitive formulation studies indicate discoloration.
Aseptic filtration is selected instead of terminal steam sterilization because terminal cycles at 121°C for 15 min may produce decomposition in related macrolides, and published data for gamithromycin terminal sterilization are limited. The solution is passed through a 0.45 μm prefilter to reduce bioburden, then a 0.22 μm sterilizing-grade filter; hydrophobic PVDF or PTFE membranes are preferred over nylon to avoid adsorption of the lipophilic free base. Filter integrity is tested before and after use by bubble point or diffusion according to the filter manufacturer’s validated values. Filtration pressure is maintained below 1.5 bar to prevent gas bubble formation from dissolved nitrogen. The filtered solution is filled into Type I borosilicate glass vials or multilayer plastic bottles with halogenated butyl rubber stoppers; fill volume tolerance is ±1.0% of target volume. Sterility testing follows Ph. Eur. 2.6.1, bacterial endotoxins follow Ph. Eur. 2.6.14, and subvisible particulate counts follow USP <788>. The labelled respiratory indications in cattle and sheep cover Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis; lung tissue concentrations exceed plasma concentrations in regulatory pharmacokinetic dossiers, but tissue concentration values are product-specific. The terminal product is administered subcutaneously for bovine and ovine respiratory disease at 6 mg/kg bodyweight; a single injection volume reaches 24 mL for a 600 kg animal. Intravenous administration is contraindicated on the reference label.
Low-dose premix production from gamithromycin API is constrained by the poor aqueous solubility and low bulk density of the active substance. A production-scale approach is stepwise dilution with a free-flowing carrier such as soybean meal, corn cob meal, or lactose monohydrate; the API is first passed through a 0.5 mm screen to break up agglomerates. Dry blending in a ribbon blender or V-type blender with a fill level between 60% and 70% of gross volume avoids dead zones above the ribbon shaft. Production-scale observations from low-density antibiotic premixes indicate that mixing at 10–12 rpm for 15–20 min produces acceptable homogeneity; longer mixing times may cause electrostatic segregation or particle attrition. The coefficient of variation for active content across 10 sampling points is controlled at ≤5.0% using Ph. Eur. 2.9.40. After blending, the premix may be converted into granules by dry granulation or low-moisture wet granulation. If wet granulation is used, the binder solution is 5–10% w/w polyvinylpyrrolidone or starch paste, and granule drying must maintain product temperature below 45°C to minimize degradation of the macrolide lactone ring. Published data for the effect of drying temperature on gamithromycin-specific degradation are limited; the 45°C limit is based on general macrolide stability trends. The finished premix is packed in multi-wall paper bags with an inner polyethylene liner, with moisture vapor transmission rate ≤1.0 g/m²/24 h. Where registered, antibiotic premixes at 10% w/w active may be incorporated into complete feed at 1–10 kg/tonne, but gamithromycin-specific feed inclusion rates are not established in major regulatory regions and must be confirmed by local marketing authorization or veterinary prescription. Feed-mill handling of medicated premix must additionally comply with EU Regulation (EC) No 183/2005 for feed hygiene, including flushbin procedures to prevent cross-contamination.
| Dosage form | Critical process limit | Compendial method |
|---|---|---|
| Injectable solution | 0.22 μm filtration, pH 5.0–5.5, fill tolerance ±1.0% | Ph. Eur. 0520, 2.6.1, 2.6.14, USP <788> |
| Premix/granules | CV ≤5.0%, product temperature ≤45°C, moisture ≤2.0% | Ph. Eur. 2.9.40, feed mill GMP |
| Oral powder/granules | Loss on drying ≤2.0%, granule sieve ≤1.0 mm, sachet seal ≥20 N | Ph. Eur. 2.9.36, ASTM F88 |
| Tablet/capsule | Hardness 30–80 N, dissolution pH 5.0 with 0.1% SLS, acceptance value ≤15 | Ph. Eur. 2.9.3, USP <711>, Ph. Eur. 2.9.40 |
For oral powder and granule dosage forms intended for drinking water or topdress, the formulation process must address the API’s poor wetting behaviour and risk of sedimentation in stock solutions. A workable form is a water-dispersible powder containing the API on a carrier system such as lactose monohydrate, colloidal silicon dioxide, and 0.1–0.5% w/w sodium lauryl sulfate as wetting agent. The API is dissolved or dispersed in an organic solvent and sprayed onto the carrier in a fluid-bed granulator; inlet air temperature is held at 35–40°C, spray rate is adjusted to maintain product temperature 28–32°C, and granules larger than 1.0 mm are milled. Exhaust relative humidity above 60% requires pre-drying of carriers to avoid wetting and particle size growth. Loss on drying is controlled at ≤2.0%; free moisture above 2.0% can promote acid- or metal-ion-catalyzed hydrolysis of the macrocyclic ester. The resulting powder or granule blend is filled into aluminium foil laminated sachets with a seal width of 8–10 mm and a burst strength above 20 N when tested according to ASTM F88. If the final use is drinking water, a stock solution at 1:100 dilution is prepared and then diluted to the final medicated water concentration. Published data for gamithromycin-specific drinking-water dosing are limited; target concentrations must be derived from the prescribing veterinarian and approved labels in the target market. A reconstituted solution should be used within 24 h unless microbial challenge data support longer holding times. The terminal oral powder or granule is an extra-label or investigational route in most regulatory regions because no harmonized gamithromycin oral dosage monograph exists.
Direct compression of gamithromycin API into tablets or capsules for non-food species requires a carrier with sufficient compressibility because the active substance typically exhibits poor flow and low compactibility as a free base. A preformulation screen under Ph. Eur. 2.9.36 powder flow methodology often yields Carr index values above 25% and Hausner ratios above 1.35, indicating cohesive flow. Micronization to a D90 below 20 μm improves content uniformity and dissolution, but it increases surface area and static charge. The addition of 1–2% w/w colloidal silicon dioxide and 50–60% w/w microcrystalline cellulose improves flow but may reduce dissolution if the API is not adequately dispersed. Wet granulation is preferred for tablets, using hydroxypropyl methylcellulose or polyvinylpyrrolidone at 3–5% w/w of dry granule mass; the wet mass is passed through a 0.8–1.0 mm screen and dried at ≤40°C to a moisture content of 1.0–2.0%. The dried granulate is lubricated with 0.5% w/w magnesium stearate, but blending time is kept below 5 min because hydrophobic lubricant overcoating retards dissolution. Tablets are compressed on an instrumented rotary press at a compression force of 5–10 kN and target hardness of 30–80 N for small veterinary tablet tools. Dissolution testing follows Ph. Eur. 2.9.3 or USP <711>; for macrolide formulations, a medium with pH 5.0 acetate buffer and 0.1% sodium lauryl sulfate improves sink conditions and discriminates batch variability. Capsules are filled by tamping pin or dosator machines; low-dose content uniformity requires pre-blending the API with a portion of diluent before final mixing to achieve acceptance value ≤15 according to Ph. Eur. 2.9.40. Published data for gamithromycin tablet/capsule dissolution specifications in registered veterinary medicine are limited; the above parameters derive from general macrolide processing practice.
Gamithromycin oral solutions, when prepared as concentrated stock liquids for drench or drinking water, are usually non-aqueous or acidified aqueous solutions that require packaging with both light and moisture barrier properties. Because the lactone ring is susceptible to acid-catalyzed hydrolysis, the solution pH is maintained at 5.0–5.5 with a buffer, and dissolved oxygen is minimized by nitrogen sparging. Amber polyethylene terephthalate bottles with a wall thickness of 0.5–0.8 mm reduce incident ultraviolet light below 380 nm; if clear multilayer bottles are used, a secondary carton with low light transmittance is required. The closure must be a polypropylene child-resistant cap with an induction-sealed aluminium foil liner; seal integrity is verified by vacuum leak testing at −0.3 bar for 10 s or dye penetration. Child-resistant closure certification follows ISO 8317. Dropper or drench nozzles are made from low-density polyethylene or polypropylene, and leachable testing follows compendial plastic packaging chapters, including Ph. Eur. 3.1 and USP <661>. At production scale, filling lines run at 60–120 bottles/min, and fill weight variation is controlled at ±2.0% for 100 mL and 250 mL presentations. The stock solution may be diluted 1:10 to 1:100 at the farm; hard water with alkalinity above 200 mg/L as calcium carbonate may raise pH and reduce solubility or accelerate degradation. Published data for gamithromycin oral solution stability in hard water are limited; the stated alkalinity threshold is based on general macrolide solution behaviour.
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Gamithromycin Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is a semisynthetic 15-membered azalide macrolide with the CAS registry number 145435-72-9, a molecular formula of C40H76N2O12, and a molecular weight of 777.04 g/mol. The product is supplied as a white to off-white crystalline powder and is controlled on the anhydrous basis with a typical HPLC assay range of 98.0%–102.0%. Injectable-grade and oral-grade models are distinguished principally by bacterial endotoxin specification, residual solvent profile, particle-size distribution, and bioburden control. The API is intended solely for further processing into finished veterinary medicinal products under conditions compliant with ICH Q7 and applicable veterinary GMP provisions; it is not administered directly to animals. The pH-dependent aqueous solubility of the free base is a central constraint across all dosage forms: solubility is low in neutral and alkaline aqueous media, while acidic media may increase solubility but can accelerate degradation in aqueous solution. Consequently, finished-product developers select non-aqueous or acidified systems only after forced-degradation testing and compatibility screening with the intended primary packaging.
No harmonised public pharmacopoeial monograph has been established for gamithromycin at the time of writing; published data for this specific configuration is limited. Regulatory dossiers therefore rely on in-house specifications aligned with VICH GL10 for impurities, VICH GL18 or ICH Q3C for residual solvents, and ICH Q7 for API manufacturing. For parenteral-grade models, bacterial endotoxin testing according to Ph. Eur. 2.6.14 or USP <85> is applied, with the acceptance criterion calculated from the maximum recommended veterinary dose. Water content is typically controlled by Karl Fischer titration because excessive moisture influences dry-powder blending and hydrolytic degradation. Residual solvents such as methanol, ethanol, and dichloromethane are controlled only if used in the final synthetic steps; if not used, they may be omitted from routine testing under a validated risk assessment. The assay method is generally HPLC with UV detection at 210 nm because the macrolide chromophore is weak; evaporative light scattering or charged aerosol detection may be used when adequate separation from related impurities is required.
| Parameter | Typical acceptance criterion | Method or standard |
|---|---|---|
| Appearance | White to off-white crystalline powder | Visual |
| Assay on anhydrous basis | 98.0%–102.0% | HPLC, in-house validated per VICH GL2 |
| Total related impurities | ≤2.0% | HPLC area normalisation |
| Residual solvents | Conform to ICH Q3C or VICH GL18 | Headspace GC |
| Water content | ≤0.5% | Karl Fischer titration |
| Sulphated ash | ≤0.1% | Ph. Eur. 2.4.14 |
| Heavy metals | ≤20 ppm | Ph. Eur. 2.4.8 or equivalent |
| Bacterial endotoxins, parenteral grade | Calculated from dose; product-specific limits are common | Ph. Eur. 2.6.14 / USP <85> |
| Particle size D90 | Product-specific, typically 10–100 µm for oral and premix grades | Laser diffraction |
For tablet and capsule manufacture, the API’s cohesive nature and hydrophobic surface require pre-processing rather than simple direct blending. In high-shear granulation, the dry powder is blended with lactose monohydrate and microcrystalline cellulose at impeller tip speeds typically below 8 m/s, followed by addition of an aqueous binder such as hypromellose or povidone. Granules are dried in fluid-bed equipment with inlet air temperature limited to 40–60 °C to avoid thermal degradation; published data for this specific configuration is limited, so forced-degradation studies should define the actual thermal limit. The dried granules are milled through a 1.0 mm screen and lubricated with magnesium stearate before compression. Tablets require taste-masking because the API has a strongly bitter amine taste; film coating with ethylcellulose or amino methacrylate copolymers is used for oral tablet models. Capsule filling by dosator or tamping-pin equipment requires the powder blend to have a Carr index below 25%; otherwise, weight variation increases on production-scale encapsulation machines. Direct compression is feasible only when a pre-granulated or spray-dried intermediate is used, because neat gamithromycin has insufficient flow and compressibility for high-speed rotary presses.
Gamithromycin inhibits bacterial protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit. It is registered in several jurisdictions for treatment and metaphylaxis of bovine respiratory disease associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. The approved cattle dose is 6 mg/kg bodyweight by subcutaneous injection in the neck. Published dossier data report a plasma elimination half-life in cattle of approximately 50–60 h, with pulmonary tissue concentrations exceeding plasma concentrations for several days after a single injection. In swine, registered indications in some countries use 6 mg/kg by intramuscular injection for respiratory pathogens such as Actinobacillus pleuropneumoniae and Haemophilus parasuis.
Tulathromycin is a triamilide macrolide approved at 2.5 mg/kg SC in cattle and has a longer plasma half-life in cattle, often reported as approximately 90 h. Tilmicosin is a 16-membered macrolide with a cattle dose of 10 mg/kg SC and is known for acute cardiovascular risk following accidental injection. Gamithromycin does not share the same acute cardiotoxic profile at the labelled dose, but all macrolide injections must avoid intravenous administration and accidental human self-injection requires immediate medical attention. The structural difference between a 15-membered azalide, a triamilide, and a 16-membered macrolide affects ribosomal binding kinetics, efflux susceptibility, and tissue residence time. Susceptibility test breakpoints are updated in CLSI VET01S; laboratories should use the current edition because historical macrolide breakpoints are not directly applicable to all azalides.
| Product | Structural class | Cattle dose | Reported half-life | Key formulation constraint |
|---|---|---|---|---|
| Gamithromycin | 15-membered azalide | 6 mg/kg SC | 50–60 h | Low aqueous solubility; non-aqueous injectable vehicles |
| Tulathromycin | Triamilide macrolide | 2.5 mg/kg SC | 90 h | Ready-to-use injectable; higher amine functionality |
| Tilmicosin | 16-membered macrolide | 10 mg/kg SC | 28–30 h | Cardiovascular risk; not for intravenous use |
| Tylosin | 16-membered macrolide | 10–20 mg/kg IM | 3–4 h | Short duration; frequent dosing; feed-grade forms |
Injectable solutions of gamithromycin present the most demanding formulation boundary because the API has low aqueous solubility at physiological pH and cannot be terminally sterilised by conventional moist heat in many proprietary formulations without chemical degradation. Non-aqueous vehicles based on glycerol formal, propylene glycol, or medium-chain triglycerides are used in registered products; exact qualitative composition is proprietary. Formulators must confirm the absence of water-induced precipitation by spiking the formulation with small volumes of aqueous buffer and observing turbidity over temperature cycles between 2 °C and 40 °C. Terminal sterilisation is replaced by aseptic filtration of the non-aqueous solution through 0.22 µm membranes where solubility and viscosity permit; otherwise, dry heat sterilisation of the API may be considered only if supported by degradation data. The pH of aqueous dilutions for oral solution should be maintained below the pKa of the tertiary amine to retain solubility, but exposure to acidic conditions beyond 24 h should be avoided to limit acid-catalysed hydrolysis.
Oral powders, granules, and premixes require different particle-size and carrier considerations than tablets. For feed premixes, the API is typically adsorbed onto a carrier such as silica or calcium carbonate before blending with feed-grade lactose or corn cob meal. The premix must maintain homogeneity during transport and metering; a target coefficient of variation below 5% across 10 sampling points is commonly specified for levigation-type mixers. Dusting is controlled by adding 0.5–1.0% w/w of food-grade vegetable oil or mineral oil, but this may reduce flow in silo discharge. Granules for oral suspension are produced by fluid-bed top-spray granulation using a binder solution; the final granule size is often targeted at 150–425 µm to balance reconstitution and mouthfeel. Drying temperature in the product bed should not exceed 50 °C unless stability data support a higher limit, because residual moisture above 2.0% may plasticise the granule and reduce chemical stability during storage. Powders intended for reconstitution should be packaged with a desiccant and protected from light, because azalide macrolides undergo photodegradation under prolonged ultraviolet exposure.
A single API grade can be used across multiple dosage forms only when the most restrictive attributes are adopted. Injectable manufacture requires the lowest endotoxin and bioburden limits, which may force oral and premix producers to accept tighter specifications than strictly necessary. Particle size presents a reverse conflict: injectable solutions benefit from finer particles for faster dissolution in non-aqueous vehicles, whereas direct-compression blends often require coarser particles to maintain flow. If a single D90 target is used, the range should be narrow enough to satisfy both dissolution rate and flow; a D90 of 20–80 µm is sometimes proposed, but published data for this specific configuration is limited. Residual solvent selection is another cross-formulation constraint: an oral grade may tolerate a higher residual solvent limit under VICH GL18, but a parenteral grade may require omission of dichloromethane or use of a higher-purity synthetic route. When one grade is specified, stability data must be generated on the grade with the largest surface area and highest initial impurity level to bracket later batches under VICH GL3 and VICH GL4 protocols.
Stability studies for gamithromycin API and its formulated products are conducted according to VICH GL3, VICH GL4, and, for finished veterinary medicinal products, VICH GL5. The API is stored in tightly closed, light-resistant containers at controlled room temperature. Forced-degradation studies typically include acid, base, peroxide, heat, and light conditions to identify impurity markers. The primary degradation products are generally N-oxide and N-demethylated species; however, published data for this specific configuration is limited and the impurity profile must be established by liquid chromatography–mass spectrometry for each manufacturing route. Gamithromycin should not be combined with strongly alkaline excipients in aqueous solution because free-base precipitation occurs above neutral pH. In solid premixes, strongly alkaline carriers such as calcium hydroxide should be avoided because free-base release and localised high pH may reduce chemical stability. The API is incompatible with strong oxidising agents and should not be irradiated for sterilisation unless the manufacturer has validated total impurity and assay retention after e-beam or gamma treatment. Processing areas with relative humidity above 60% require pre-dried excipients and controlled transfer to prevent moisture uptake and caking of fine API powders.
