| HS Code | 101324 |
| Chemical Name | N,N-dimethyl-5-[({2-[(1-methyl-1H-imidazol-5-yl)methyl]sulfanyl}ethyl)amino]furan-2-carboxamide |
| Molecular Formula | C13H22N4O3S |
| Molecular Weight | 314.41 g/mol |
| Cas Number | 66357-35-5 |
| Description | White to off-white crystalline powder, freely soluble in water and methanol, slightly soluble in chloroform |
| Solubility | Freely soluble in water, ethanol, and methanol; sparingly soluble in chloroform |
| Ph Range | pH of 5% aqueous solution is between 4.5 and 6.0 |
| Assay Content | 99.0% to 101.0% on dried basis |
| Storage Condition | Store in tightly closed containers, protected from light, at room temperature 15-30°C |
As an accredited Ranitidine 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 25kg sealed drums with double polyethylene liners, ensuring purity and stability for veterinary pharmaceutical formulations. |
| Container Loading (20′ FCL) | One 20′ FCL container loads palletized, drummed Ranitidine Veterinary Grade API, secured for safe transport of formulations. |
| Shipping | Shipments of Ranitidine Veterinary Grade API are packed in sealed, moisture-proof containers with tamper-evident seals. Transport occurs in ventilated, temperature-controlled vehicles to prevent degradation. Ensure compliance with veterinary drug regulations, proper hazardous material labeling, and secure documentation. Avoid direct sunlight and excessive humidity during transit and storage. |
| Storage | Store Ranitidine Veterinary Grade API in tightly sealed, light-resistant containers in a cool, dry, well-ventilated area below 25°C. Protect from moisture, excessive heat, and direct sunlight. Keep away from oxidizing agents and incompatible materials. Avoid prolonged exposure to air and humidity; use original packaging until dispensing. |
| Shelf Life | Shelf life: 24 months when stored in a cool, dry place, protected from light and moisture, in original sealed containers. |
In tablet compression suites serving companion-animal gastroenterology, ranitidine hydrochloride is formulated at 150 mg or 300 mg active per tablet, corresponding to 30–45 wt% of a 400–650 mg core. The hydrochloride salt is hygroscopic after milling, so pre-drying is required when ambient relative humidity exceeds 60%. The granulation process uses a low-shear planetary mixer with an aqueous povidone K30 binder solution, followed by fluid-bed drying at 45–60°C to residual moisture of 1.5–2.5%. Residual moisture above 2.5% has been associated on production-scale rotary presses with edge capping and lamination; compression force is held between 8 kN and 15 kN to achieve hardness of 5–8 kp and friability below 1.0%. Finished tablet cores are film-coated with HPMC-based coatings and tested against USP <905> for content uniformity and USP <711> for dissolution. Finished-product cGMP requirements fall under 21 CFR 210/211 and EU GMP Part 4; stability testing follows 21 CFR 211.166. Residual solvent limits are governed by VICH GL18, and nitrosamine-specific release testing is applied because ranitidine can form N-nitrosodimethylamine under heat and humectant stress. Terminal product types are scored oral tablets for canine and feline clinics. Formula addition ratio: 30–45 wt% in the tablet core.
Dissolution of the hydrochloride salt in purified water is not the throughput-limiting step, because ranitidine HCl has high aqueous solubility; the main limitations are photodegradation, pH drift, and preservative interaction in multi-dose containers. A 15 mg/mL oral solution corresponds to 1.5% w/v ranitidine HCl. The batch is prepared in a jacketed stainless-steel vessel at 20–25°C with propeller agitation at 300–500 rpm. The API is dissolved first, then citric acid and disodium phosphate are added to hold pH at 5.5–6.5. Sodium benzoate 0.1% w/v or potassium sorbate 0.1% w/v is included as preservative, and preservative efficacy is validated to USP <51> and Ph. Eur. 5.1.3. The bulk solution is filtered through a 0.45 µm polypropylene cartridge and filled into amber PET or type III glass bottles to limit light-induced colour formation. Elemental impurities are controlled under ICH Q3D using USP <232> and USP <233> methods; residual solvents follow VICH GL18. In-process pH is rechecked after a 12 h hold because a shift greater than 0.3 units accelerates colour development. Terminal product types are multi-dose oral solutions for veterinary clinics, equine hospitals, and zoological institutions. Formula addition ratio: 1.5% w/v.
Aqueous parenteral batches are compounded under nitrogen inertion because ranitidine HCl is susceptible to oxidative discoloration and light-catalysed degradation. The standard veterinary injection is formulated at 25 mg/mL ranitidine HCl, equivalent to 2.5% w/v. Water for injection is sparged with nitrogen until dissolved oxygen remains below 1.0% of saturation; the API and phenol 0.5% w/v are then dissolved in a closed stainless mixing vessel at 20–25°C. pH is adjusted to 5.0–6.0 with dilute hydrochloric acid or sodium hydroxide. The solution is passed through a 0.22 µm PVDF membrane and aseptically filled into amber type I glass vials under nitrogen overlay. Published data for terminal sterilisation of this specific veterinary configuration at 121°C for 15 min are limited; aseptic processing is typically retained because thermal exposure can increase N-nitrosodimethylamine formation risk. Sterility is validated to USP <71>, bacterial endotoxin limits to USP <85>, and container closure integrity to USP <1207>. The aseptic filling line operates under EU GMP Annex 1 and 21 CFR 211.167; API quality is maintained under ICH Q7. Terminal product types are multi-dose parenteral solutions for intravenous or intramuscular use in equine and small-animal hospitals. Formula addition ratio: 2.5% w/v.
| Formulation route | API addition ratio | Critical process threshold | Compliance standard |
|---|---|---|---|
| Tablet cores | 30–45 wt% | Granule moisture max 2.5%; hardness 5–8 kp | USP <905>; USP <711>; VICH GL18 |
| Oral solution | 1.5% w/v | pH 5.5–6.5; light-protective filling | USP <51>; Ph. Eur. 5.1.3 |
| Injection | 2.5% w/v | Dissolved oxygen below 1.0%; filtration 0.22 µm | USP <71>; USP <85> |
| Granules/powder sachets | 20–45 wt% | Particle cut 250–500 µm; moisture max 2.0% | USP <795>; VICH GL18 |
| Capsules | 5–20 wt% | Granule size 0.5–1.0 mm; lubricant 0.5–1.0 wt% | USP <905>; 21 CFR 211.110 |
| Premix carrier | 5–10 wt% | Carrier nitrite max 5 ppm; storage max 25°C | USP <795>; VICH GL18 |
For nasogastric acid-suppressive drenches prepared in equine hospital pharmacies, ranitidine hydrochloride granulation begins as a dry pre-blend of lactose monohydrate, microcrystalline cellulose, and povidone K30. The API is added at 20–45 wt% of the dry granulate; a 300 mg ranitidine dose is delivered with 0.7–1.5 g of finished granules. High-shear granulation is followed by fluid-bed drying at 40–50°C to residual moisture below 2.0%, then oscillating sieving retains the 250–500 µm fraction. The lower size cut is not cosmetic: fine particles below 250 µm segregate during sachet filling and the hygroscopic dust sticks to stainless contact surfaces, increasing weight variability and cleaning load. Granules are filled into foil-lined sachets for direct oral administration or reconstituted with purified water in oral dosing syringes at point of care. Nonsterile compounding is governed by USP <795>, residual solvents are controlled under VICH GL18, and blend uniformity is evaluated using USP <905> principles. Terminal product types are oral powder sachets, reconstituted suspensions, and nasogastric drench preparations for equine patients. Formula addition ratio: 20–45 wt% in dry granulate.
When low-dose capsules are required for feline patients below 5 kg bodyweight, direct filling of milled ranitidine HCl without densification produces high weight variability because the API has low bulk density and poor flow. Roller compaction with microcrystalline cellulose and crospovidone is therefore used at API levels of 5–20 wt%. Ribbons are milled through a 1.0 mm screen; the resulting granules have a mean particle size between 0.5 mm and 1.0 mm. Magnesium stearate is added at 0.5–1.0 wt% before filling on dosator or dosing-disc capsule machines. Weight variation is controlled to USP <905> and dissolution to USP <711>. Nitrosamine testing is appended to the release panel because roller compaction generates local frictional heat in the compaction zone, which can promote ranitidine-related N-nitrosodimethylamine formation if nitrite sources are present. Capsule shell size ranges from size 3 to size 1 depending on whether the filled dose is 10 mg, 30 mg, or 75 mg; fill weight is held between 100 mg and 250 mg. In-process sampling complies with 21 CFR 211.110, and residual solvent control follows VICH GL18. Terminal product types are uncoated hard gelatin or hypromellose capsules for canine and feline gastroprotection. Formula addition ratio: 5–20 wt% of granulate.
Premix-type intermediates for in-water administration are manufactured with nitrite-screened carriers to minimise nitrosamine formation during storage and use. Ranitidine HCl is incorporated at 5–10 wt% of a lactose/dextrose dry carrier, equivalent to 50–100 g ranitidine per kg premix. The carrier is screened for nitrite and nitrate and rejected if nitrite exceeds 5 ppm, because acidified drinking water or molasses-based delivery systems can accelerate N-nitrosodimethylamine generation from ranitidine-related impurities. Blending is performed in a V-blender or ribbon blender at 15–25 rpm for 20–30 min; the premix is then filled into foil-lined bags with desiccant sachets and stored below 25°C. Residual solvent testing follows VICH GL18. Where the premix is used as a pharmacy compounding input rather than an approved medicated feed article, USP <795> governs nonsterile preparation and labelling. Terminal product types include dry oral dosage adjuvants, in-water drench intermediates, and carrier-stabilised powders for reconstitution in veterinary teaching hospitals. Manufacturers should confirm national regulatory status for in-feed medicated use, because ranitidine hydrochloride is not uniformly approved as a feed-additive premix across jurisdictions. Formula addition ratio: 5–10 wt% in dry carrier.
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Ranitidine Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is supplied as ranitidine hydrochloride, CAS 66357-35-5, molecular formula C13H22N4O3S·HCl, molar mass 350.87 g/mol. The product identifier commonly includes the base form, salt form, and a manufacturer grade code that differentiates direct-compression particle size, injectable-grade bioburden, or micronized suspension grade. The material is a white to pale yellow crystalline powder with aqueous solubility suitable for liquid dosage forms and pH-dependent stability. Pharmacologically, it is a competitive histamine H2-receptor antagonist that reduces basal and stimulated gastric acid secretion; in companion animal medicine this activity is applied to gastritis, gastric ulcer prophylaxis, reflux esophagitis, and acid-related mucosal injury in dogs, cats, and horses. The API is not a ready-to-administer premix or finished formulation. It is released against compendial monographs and intended for further GMP processing into immediate-release tablets, capsules, oral powders, granules, feed premixes, and injectable or oral solutions. Veterinary-grade documentation is aligned with VICH GL3 and VICH GL4 stability expectations, but the chemical purity and impurity specifications are not automatically looser than those for human-grade material. The main difference is that veterinary supplier dossiers emphasize companion-animal and horse exposure data, stability under veterinary climatic zones, and audit trails appropriate for veterinary marketing authorizations. A veterinary grade API having the same CAS and monograph identity as the human drug substance must still be qualified in each final dosage form, because the excipient matrix and manufacturing process determine finished product stability and bioequivalence. The bulk API is not intended for direct administration to animals; it is a processing input for licensed or pharmacy-compounded finished dosage forms.
Release specifications for the API follow the USP Ranitidine Hydrochloride monograph and the corresponding Ph. Eur. monograph, with additional route-specific controls. The assay limit is 98.0–102.0% on the dried basis by HPLC. Related substances are controlled under ICH Q3A thresholds: reporting 0.05%, identification 0.10%, and qualification 0.15%. Residual solvents are limited under ICH Q3C; ethanol, acetone, and isopropyl alcohol are the most common residual solvents in the final crystallization and are typically controlled to 5000 ppm or lower when present. Water content by Karl Fischer titration is typically ≤0.75%. Elemental impurities are assessed by ICH Q3D, with results expressed for Class 1 and Class 2A elements. For injectable-grade material, bacterial endotoxin is controlled to ≤0.50 EU/mg when the final route is intravenous or intramuscular. Identity is confirmed by IR and HPLC retention time. Crystalline form is monitored by X-ray powder diffraction because ranitidine hydrochloride is polymorphic; an uncontrolled form change can alter solubility, dissolution, and blend behavior in tablets.
Chromatographic purity is performed on a C18 column with a mobile phase consisting of phosphate buffer and methanol or acetonitrile; system suitability includes resolution of ranitidine from related compound A, tailing factor, and relative standard deviation. For residual solvent analysis, headspace gas chromatography with flame ionization detection is used; method sensitivity must comply with the concentration limits in ICH Q3C. The polymorph form is not directly specified in all monographs, but manufacturers control it because powdered X-ray diffraction patterns distinguish Form 1, Form 2, and the amorphous form. For wet granulated or aqueous coated processes, the API lot should be reviewed for crystal habit and residual surface water because crystalline ranitidine hydrochloride can occlude solvent and influence drying endpoints.
| Specification parameter | Typical release criterion | Method |
|---|---|---|
| Assay on dried basis | 98.0–102.0% | HPLC |
| Water content | ≤0.75% | Karl Fischer, USP <921> |
| Residual solvents | ≤5000 ppm for Class 3 solvents used | GC-HS |
| Related substances | individual unspecified ≤0.10%; total ≤1.0% | HPLC |
| Bacterial endotoxin, injectable | ≤0.50 EU/mg | USP <85> |
| Particle size, direct compression | d(0.5) 80–150 µm | laser diffraction |
| Particle size, suspension/premix | d(0.5) ≤50 µm | laser diffraction |
Under accelerated stress conditions, ranitidine hydrochloride can undergo hydrolytic cleavage of the nitroethenediamine side chain and oxidation of the thioether bridge. The degradation products are separated by reverse-phase HPLC with UV detection at 230 nm. Storage therefore requires well-closed, light-resistant containers below 25 °C, with desiccant in climatic zones exceeding 60% relative humidity. Stability is evaluated under VICH GL4 zones, typically 25 °C/60% RH and 40 °C/75% RH for accelerated conditions. For moisture-sensitive API, desiccant quantity is calculated from the moisture vapor transmission rate of the primary package. Aluminum foil or PVdC-coated PVC blisters are used for tablets; HDPE containers with heat-sealed liners are used for bulk API. Bulk containers should be re-sealed under low humidity after sampling, because repeated opening can introduce moisture that increases adhesive aggregation and nitrosamine formation risk.
Nitrosamine control has become the decisive quality parameter for this molecule. Ranitidine can generate N-nitrosodimethylamine, NDMA, through a self-degradation pathway accelerated by heat and moisture, and finished-product stability must include a validated LC-MS/MS method capable of quantitating NDMA at or below 96 ng/day acceptable intake. This control aligns with USP <1469> and applicable regional guidance. Veterinary grade API manufacturers therefore supply a nitrosamine risk assessment and batch-specific LC-MS/MS data. Material with NDMA above the regulatory limit is rejected; blending of non-conforming API is not permitted. Published data for long-term NDMA formation in some veterinary premix matrices is limited, so formulators should conduct matrix-specific stability studies rather than extrapolate from neat API data.
In tablet and capsule manufacture, direct compression of ranitidine hydrochloride is feasible only when the particle-size distribution, bulk density, and flow are matched to the press. Powder flow is characterized by Hausner ratio and Carr index; a Hausner ratio above 1.40 typically requires a flow aid or granulation. Low-dose tablet strengths below 15 mg require geometric dilution in a bin blender or V-blender with intensifier bar, followed by compression on a rotary tablet press equipped with forced feeder. Segregation is reduced when the API d(0.9) is controlled relative to the filler d(0.5). Dry granulation by roller compaction is preferred over wet granulation because residual water can accelerate ranitidine degradation. Roller compaction parameters such as roll force, roll speed, and screen size affect granule porosity and tablet tensile strength; overly dense ribbons produce hard granules that reduce tablet strength, while friable ribbons produce high fines and weight variation. Granules are milled to a target particle size appropriate for the tablet press and lubricated with magnesium stearate at 0.25–0.75 wt%, with lubrication over 5 min avoided to prevent overlubrication. Dissolution testing uses USP <711> apparatus II at 50 rpm in 900 mL dissolution medium; Q values are defined in the individual finished product monograph, not in the API monograph. Capsule filling requires attention to powder bridging and flow, particularly at fill weights below 100 mg; tackiness can be reduced by keeping the relative humidity below 45% in the filling suite.
Excipient compatibility is not assumed. Ranitidine hydrochloride can interact with reducing sugars in the presence of moisture through Maillard-type discoloration, so formulations for chewable tablets or palatable oral powders should avoid prolonged wet contact with lactose or dextrose unless protective coating is used. Microcrystalline cellulose, dibasic calcium phosphate, and pregelatinized starch are commonly evaluated as dry binders. Compressibility of ranitidine hydrochloride itself is moderate; it is rarely processed as a neat compact. The blend is compressed to hardness 5–10 kp for tablets depending on diameter and disintegration requirement, while friability is kept below 1.0% under USP <1216>. Tablet hardness should not be raised to improve elegance at the expense of dissolution; the development report for each strength must link hardness, disintegration, and dissolution profiles.
For carrier-based premixes and granules intended for feed or oral administration, the main technical risk is non-homogeneous distribution of a potent API in a large-volume carrier. Ranitidine hydrochloride is soluble in water, which supports deposition by spraying onto lactose, dextrose, or microcrystalline cellulose carriers in a fluid-bed granulator. The API solution is sprayed at 10–20% solids with inlet air at 40–60 °C, because higher temperatures accelerate degradation. Alternatively, gentle blending in a ribbon mixer or ploughshare mixer can be used when the API is pre-blended with a fine diluent and then extended stepwise. Content uniformity in premixes is evaluated by taking 10 samples from different locations and calculating relative standard deviation; a target RSD of ≤5.0% is common for high-potency premixes. Carryover and rinse-down between batches must be assessed because ranitidine hydrochloride is water-soluble and can leave residues in stainless steel equipment. Cleaning validation limits are calculated from the lowest therapeutic dose, batch size, and maximum allowable carryover in the next product. If the premix is incorporated into pelleted feed, the API must survive conditioning at 70–85 °C for 30–60 s; this requires a pre-conditioning stability study. Use in food-producing species is not authorized in many jurisdictions; veterinary formulators must verify MRL status and withdrawal periods before combining this API into medicated feed for animals intended for human consumption.
Because injectable solutions require low bioburden, controlled endotoxin, and particulate matter that are not relevant to dry premix use, the API grade must be selected at the outset. Ranitidine hydrochloride is dissolved in Water for Injection at 25 mg/mL or 50 mg/mL and buffered to pH 6.5–7.5 before terminal sterilization by autoclaving at 121 °C for 15 min. The solution is filled into Type I glass vials and tested for subvisible particulates under USP <788>. The API must pass bacterial endotoxin limits under USP <85>; endotoxin reduction before compounding is not a substitute for low-endotoxin API. Solutions diluted in 0.9% sodium chloride or 5% dextrose should be used within 24 h at room temperature unless the admixture has been shown stable for longer by endpoint analysis. Polyvinyl chloride and polyolefin containers are generally compatible, but contact studies are required if the final product is stored in plastic ampoules or prefilled syringes.
Oral solutions and suspensions made from the same API require a preservative system, such as sodium benzoate 0.1% or potassium sorbate 0.1%, and a pH below 5.0 if chemical stability permits. High pH increases the free-base precipitation risk; low pH accelerates degradation, so the formulation pH is typically held at 4.5–5.5 for oral liquids. Protective packaging is required because ranitidine hydrochloride is light-sensitive. Terminal sterilization of multi-dose injectable vials containing a preservative should be validated in the final container, because the API can interact with phenolic preservatives at elevated temperature. Nitrogen flushing of headspace and chelation of trace metals in solution can further reduce oxidative color formation during storage. For oral powders and granules intended for reconstitution, the powder blend must be free-flowing and readily dispersible; the reconstituted suspension should be evaluated for dose delivery from the supplied measuring device, not only for chemical stability.
Ranitidine HCl is a furan-ring H2 antagonist. Cimetidine is an imidazole derivative and inhibits CYP1A2, CYP2C9, and CYP3A4; ranitidine has lower CYP affinity and fewer drug interactions. Famotidine, a thiazole derivative, is more potent on a molar basis and has a longer duration of action in dogs when dosed at lower milligram quantities. Omeprazole is a proton-pump inhibitor acting at the H+/K+-ATPase pump; it inhibits acid more completely but has delayed onset and requires enteric protection in oral forms. These differences affect formulation: cimetidine has a bitter taste requiring substantial masking; ranitidine HCl is bitter but available as coated tablets; famotidine is low-dose and requires high-shear mixing for content uniformity; omeprazole is acid-labile and requires enteric coating or buffering. In dogs, ranitidine is used at oral doses of 1–2 mg/kg every 8–12 h; in horses, 6.6 mg/kg every 8 h is sometimes cited in clinical literature. These doses generate a wide range of tablet strengths, from 15 mg to 300 mg, and support the need for multiple API particle-size grades. Ranitidine does not require the enteric protection of omeprazole and is less likely than cimetidine to alter the clearance of co-administered drugs. It is not interchangeable with proton-pump inhibitors on a milligram basis, and veterinarians must not substitute famotidine doses without adjusting for potency and dosing interval.
| API | Chemical class | Relative H2-receptor potency | CYP inhibition | Veterinary formulation implication |
|---|---|---|---|---|
| Cimetidine | imidazole | 1 (reference) | CYP1A2, CYP2C9, CYP3A4 | bitter taste; multiple daily dosing; higher interaction risk |
| Ranitidine | furan | 4–10× cimetidine | weak | tablet, injection, oral liquid; nitrosamine control required |
| Famotidine | thiazole | 20–50× cimetidine | negligible | low-dose; content uniformity challenges; longer duration |
| Omeprazole | benzimidazole proton-pump inhibitor | not H2-competitive | CYP2C19 | acid-labile; enteric coating or buffered oral form; delayed onset |
