| HS Code | 699004 |
| Product Name | Sulphadimidine Pharma Grade API |
| Chemical Name | 4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide |
| Molecular Formula | C12H14N4O2S |
| Molecular Weight | 278.33 g/mol |
| Cas Number | 57-68-1 |
| Appearance | White to off-white crystalline powder |
| Solubility | Sparingly soluble in water; soluble in acetone; slightly soluble in ethanol; freely soluble in dilute mineral acids and alkali hydroxides |
| Melting Point | 176-180 degree Celsius |
| Assay Purity | 99.0% to 101.0% on dried basis |
| Storage Conditions | Store in well-closed containers, protected from light and moisture, at controlled room temperature |
| Dosage Form Suitability | Suitable for tablet, capsule, granule, oral, and injectable formulations |
As an accredited Sulphadimidine Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Supplied in 25 kg drums, double polythene-lined, tamper-evident sealed, with labels for pharmacopoeial API for oral tablets, capsules, granules, and injectables. |
| Container Loading (20′ FCL) | A 20′ FCL contains Sulphadimidine Pharma Grade API, packed in sealed drums/cartons, palletized, secured, labelled, and documented for pharmaceutical use. |
| Shipping | Sulphadimidine Pharma Grade API ships in sealed, light-resistant, moisture-proof packaging to maintain purity. Transport under dry, temperature-controlled conditions, avoiding extreme heat. Ensure compliance with pharmaceutical shipping regulations and provide complete documentation, including COA and MSDS. Suitable for oral and injectable formulations with secure, tamper-evident delivery worldwide. |
| Storage | Store Sulphadimidine Pharma Grade API in a cool, dry, well-ventilated area, protected from light, moisture, and excessive heat. Keep the container tightly closed when not in use and away from incompatible substances, oxidizers, and foodstuffs. Ensure proper labeling and use suitable personal protective equipment during handling. Follow manufacturer’s guidelines for expiry and temperature range. |
| Shelf Life | Shelf life is 36 months from manufacture when stored in tightly sealed containers, protected from light, moisture, and heat. |
Sulphadimine (4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide) is received as a white to off-white crystalline powder. Unprocessed material frequently exhibits a needle-like crystal habit and electrostatic behaviour. Direct compression of high-dose veterinary tablets is therefore limited to API batches with a median particle size d50 75–150 µm. A typical direct-compression matrix contains microcrystalline cellulose 20–35% w/w, anhydrous dibasic calcium phosphate 10–20% w/w, croscarmellose sodium 2–5% w/w, colloidal silicon dioxide 0.5–1.0% w/w, and magnesium stearate 0.5–1.0% w/w. On a rotary tablet press operating at 10–25 kN compression force, 500 mg tablets are produced at a hardness of 60–100 N. Lubrication time with magnesium stearate beyond 5 minutes reduces tensile strength by over-lubricating the fillers. Compression speed above 30 rpm can induce capping if the formulation contains entrapped air. Uniformity of dosage units is assessed by Ph. Eur. 2.9.40 or USP <905>. Disintegration is measured by Ph. Eur. 2.9.1 with water at 37 °C and a limit of 15 minutes for uncoated tablets. Dissolution testing for high-dose tablets uses 900 mL of phosphate buffer at pH 6.8 and a paddle speed of 50 rpm. If dissolution fails because of the poor intrinsic solubility of the free acid, the formulation is shifted to wet granulation with sodium bicarbonate or the API is milled to d90 ≤50 µm. Terminal products include 500 mg, 1000 mg, and large-animal 5 g bolus tablets.
When capsule formulations exceed 60% w/w sulphadimine, the direct fill blend tends to segregate and flow poorly. High-shear granulation with polyvinylpyrrolidone 3–5% w/w dissolved in purified water converts the API into dense spherical granules. The wet mass is passed through a 1.0–2.0 mm screen and dried in a fluid-bed dryer to a loss on drying ≤2.0% w/w. Extragranular microcrystalline cellulose 10–15% w/w and crospovidone 2–4% w/w are added before encapsulation. The resulting granule size is controlled to 0.2–0.8 mm. Capsule filling on a dosator or tamping-pin machine is set to a fill weight variation ≤±5% from the mean. Hard gelatin or hypromellose capsules of 250 mg or 500 mg sulphadimine are then filled. The dissolution test uses 900 mL phosphate buffer at pH 6.8 and basket speed 100 rpm. The endpoint is not less than 75% dissolved at 45 minutes unless a pharmacopoeial monograph specifies an alternative Q value. Moisture ingress above 2.5% in the capsule shell may lead to brittle fracture, so primary packaging is specified to maintain relative humidity below 60%.
For drinking-water medication, sulphadimine is formulated as an effervescent or dispersible granule rather than a plain physical mixture. The granule contains anhydrous citric acid and sodium bicarbonate in a stoichiometric ratio that yields a solution pH of 6.5–7.5 after complete effervescence. A wetting agent such as sodium lauryl sulfate at 0.05–0.2% w/w reduces particle surface agglomeration. Polyvinylpyrrolidone at 2–4% w/w acts as the binder in a fluid-bed top-spray granulation. Inlet air temperature is maintained at 50–70 °C, product temperature at 30–40 °C, and final loss on drying at ≤1.5% w/w. The dried granules are sieved to 0.2–0.8 mm. A single sachet is expected to disperse in 1 L of water at 25 °C within 3 minutes with gentle stirring. The resulting solution is intended for oral administration via drinking water and should be consumed within 24 hours. Prolonged standing in hard water can reduce dissolved potency through precipitation of poorly soluble salts. Uniformity of mass for single-dose sachets is tested by Ph. Eur. 2.9.5 or USP <905>. HPLC assay after reconstitution confirms that the solution contains the declared content of sulphadimine. Terminal products include 10 g, 100 g, and 1 kg sachets or tubs for group treatment in pigs and poultry.
Injectable sulphadimine is prepared as a sterile aqueous solution of sulphadimine sodium. The free acid is dissolved in water for injections by pH adjustment with sodium hydroxide, with a final target pH of 9.0–10.5. At pH below 8.5 the ionised fraction decreases and visible precipitation of the free acid can occur during temperature cycling. At pH above 10.5 alkaline hydrolysis of the sulphonamide linkage accelerates and generates sulphanilic acid-related impurities. A typical formulation contains sulphadimine sodium equivalent to 33.3% w/v sulphadimine base, sodium metabisulphite 0.1% w/v as antioxidant, disodium edetate 0.01% w/v as chelator, and water for injections up to volume. The solution is sparged with nitrogen until dissolved oxygen is <1 mg/L. It is then filtered through a 0.22 µm sterilising-grade membrane into amber Type I glass ampoules or vials. Terminal sterilisation is performed in a saturated steam autoclave at 121 °C for 15 minutes, with a target F0 value not less than 12 minutes. Headspace oxygen is excluded by nitrogen flushing before closure. The finished injection is tested for sterility by Ph. Eur. 2.6.1, bacterial endotoxins by Ph. Eur. 2.6.14, and sub-visible particulate contamination by Ph. Eur. 2.9.19. Visible particles are controlled by inspection against a black-and-white panel. The final product is intended for intravenous, intramuscular, or subcutaneous use in cattle, pigs, sheep, and goats when prescribed by a veterinarian.
| Process variable | Acceptable range or limit | Monitoring method | Observed failure mode |
|---|---|---|---|
| Final solution pH | 9.0–10.5 | Potentiometric pH meter | Precipitation below 8.5; impurity increase above 10.5 |
| Dissolved oxygen before filling | <1 mg/L | Optical DO sensor | Oxidative colour formation in amber glass |
| Sterilising filter integrity | Bubble point per membrane manufacturer | Diffusion or bubble point test | Breach leads to sterility failure |
| Autoclave F0 | ≥12 minutes | Thermocouple and biological indicator | Insufficient lethality |
In oral suspension manufacture, micronised sulphadimine is dispersed in a preserved aqueous vehicle. The API is milled to a particle size d90 ≤20 µm to reduce sedimentation and improve resuspendability. Wetting is achieved with polysorbate 80 at 0.1–0.5% w/w. Suspension structure is provided by xanthan gum at 0.3–0.5% w/w. Sodium benzoate at 0.1–0.2% w/w serves as the preservative. The pH is adjusted to 4.5–5.5 with citric acid or sodium hydroxide to reduce chemical hydrolysis while maintaining rheological stability. High-shear homogenisation is conducted at 3000–5000 rpm for 15–30 minutes. The final viscosity is controlled to 500–1500 mPa·s using a Brookfield viscometer at 25 °C. Sedimentation volume ratio is specified as >0.9 after 24 hours. Redispersibility after gentle shaking must be complete. This format is used when animals cannot tolerate tablets or when precise body-weight-adjusted dosing is required. Terminal products include oral suspension 100 mg/mL and drench paste packaged in multi-dose bottles or dial-a-dose syringes.
Fixed-dose combinations of sulphadimine and trimethoprim are formulated at a 5:1 weight ratio because the sequential blockade of bacterial folate synthesis is most frequently described at this ratio. A representative tablet contains 400 mg sulphadimine and 80 mg trimethoprim. Direct blending of the two APIs is not sufficient for content uniformity because trimethoprim is a low-dose component with poor compressibility and may segregate. Each active is therefore granulated separately. Sulphadimine is granulated with polyvinylpyrrolidone 3–5% w/w; trimethoprim is wet-massed with lactose monohydrate and maize starch. The two granulates are combined in a tumble blender for 15 minutes. Magnesium stearate 0.5–1.0% w/w is added for the final 3–5 minutes only. Tablets are compressed at 12–20 kN to a hardness of 70–110 N. Wet granulation of trimethoprim at pH below 4.0 should be avoided because trimethoprim dissolves and may recrystallise as hard agglomerates during drying. The finished tablets are tested for both actives by HPLC. The dissolution test uses 900 mL of phosphate buffer at pH 6.8 and paddle speed 50 rpm; both components are quantified at the same sampling time. Terminal products include 400 mg/80 mg tablets and 200 mg/40 mg oral suspension.
| Quality attribute | Method | Specification |
|---|---|---|
| Uniformity of dosage units | Ph. Eur. 2.9.40 | AV ≤ 15 |
| Dissolution | Ph. Eur. 2.9.3 | Q = 75% at 45 minutes |
| Disintegration | Ph. Eur. 2.9.1 | ≤15 minutes |
| Related substances | HPLC pharmacopoeial monograph | Individual unknown ≤0.2%, total ≤1.0% |
| Water content | Karl Fischer | ≤1.5% w/w |
A further downstream application is the production of pharmaceutical granules for in-feed medication. The granules are designed to be blended into compound feed at a mixer coefficient of variation ≤5%. Granule size between 250 µm and 500 µm reduces segregation against ground maize and soybean meal. Dry granulation by roll compaction is preferred when the API is heat-sensitive. Wet granulation is used only if the drying step can be held below 70 °C. During pelleted feed processing, temperatures above 80 °C increase the risk of sulphadimine degradation, although published data for prolonged residence time in commercial pellet mills is limited. The finished premix is assayed by HPLC after milling and blending to confirm that the declared sulphadimine content is maintained throughout the batch. Terminal products include 10%, 20%, and 50% w/w sulphadimine premixes for authorised veterinary use.
Competitive Sulphadimidine Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
Sulphadimidine Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is supplied in two principal chemical forms: the free base and the sodium salt. The base is identified chemically as 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide, CAS 57-68-1, molecular formula C12H14N4O2S, relative molecular mass 278.33. The sodium salt is the water-soluble derivative used for injectable liquid formulations. Compendial monographs include Ph.Eur. and BP Sulfadimidine and USP Sulfamethazine; the monograph for the sodium salt applies to the injectable grade. The base appears as a white to yellowish-white crystalline powder, is practically insoluble in water, soluble in acetone, and soluble in dilute mineral acids and alkali hydroxides. The sodium salt dissolves freely in water, forming an alkaline solution that is processed under pH control.
The supplied model designations are the base compendial grade, the micronized base grade for oral solid dosage forms, and the injectable sodium salt grade for parenteral liquids. The base and sodium salt are not interchangeable in production; conversion of the base to the sodium salt requires a separate validated salification and drying step. For solid oral dosage forms, the manufacturer assigns particle size grades according to the intended granulation route and the finished-product content uniformity requirement.
Release testing covers identity, purity, water content, sulphated ash, related substances, residual solvents, elemental impurities where required, and assay. The values in the accompanying table are representative general pharmacopoeial limits for the base; the exact limits must be confirmed against the current monograph version in the relevant territory because pharmacopoeial revisions change limit tables over time. For the injectable sodium salt grade, additional release specifications are added for bacterial endotoxins, bioburden, colour of solution, and particulate matter after dissolution.
| Parameter | Acceptance criterion | Reference method |
|---|---|---|
| Appearance | White or yellowish-white crystalline powder | Visual examination |
| Identification | Infrared spectrum concordant with chemical reference substance; TLC concordant | Ph.Eur. 2.2.24, 2.2.27 |
| Loss on drying | ≤ 0.5% | Ph.Eur. 2.2.32, 100–105 °C |
| Sulphated ash | ≤ 0.1% | Ph.Eur. 2.4.14 |
| Assay (dried basis) | 99.0–101.0% | Monograph titrimetric or HPLC method |
| Related substances | Individual impurity and total impurity limits per current monograph | Ph.Eur. 2.2.29 |
| Heavy metals or elemental impurities | ≤ 20 ppm where specified; ICH Q3D option if applied | Ph.Eur. 2.4.8 / 5.20 |
Residual solvents are controlled by Ph.Eur. 5.4 or ICH Q3C. In practice, a manufacturer using ethanol in the final crystallisation must demonstrate ethanol below the permitted concentration for the finished drug product, not merely for the API. The injectable sodium salt grade is tested for bacterial endotoxins using Ph.Eur. 2.6.14, with the limit derived from the intended maximum parenteral dose.
For tablet, capsule, and granule manufacture, the particle size distribution of the base is a critical material attribute because sulfadimidine has poor aqueous solubility. A milled grade with d90 below 150 µm and d50 between 50 µm and 90 µm is generally suitable for wet granulation in high-shear mixers or fluid-bed granulators. In direct compression and low-dose capsule blends, a micronized grade with d90 below 25 µm is typically required to achieve content uniformity under Ph.Eur. 2.9.40. The trade-off is flow: micronized sulfadimidine can exhibit increased cohesion and may require colloidal silicon dioxide at 0.2–0.5% w/w and microcrystalline cellulose as a dry binder to maintain acceptable die filling on rotary tablet presses.
Wet granulation with purified water or an aqueous binder solution is possible because the base remains chemically stable in water at neutral pH, but the granulation endpoint is sensitive to overwetting due to the hydrophobic surface of the crystalline powder. In production-scale high-shear granulators with impeller tip speeds of 5–10 m/s and chopper speeds of 1500–3000 rpm, excessive water addition produces dense granules that require prolonged disintegration. Granule moisture before drying is typically held at 1–3% to avoid overcompression; dried granule loss on drying is returned to ≤ 0.5%. Fluid-bed drying inlet air at 60–70 °C is used while the product temperature is maintained below 50 °C to prevent yellowing.
Tablet compression of sulfadimidine granules is usually run at hardness values of 50–80 N for conventional immediate-release tablets, with sodium starch glycolate or croscarmellose sodium at 2–4% w/w as disintegrant. Capsule filling uses granulated material with bulk density in the range 0.45–0.55 g/mL; variation in bulk density across API lots requires adjustment of fill volume or slugging precompression. Dissolution testing follows Ph.Eur. 2.9.3 or USP 711. Because dissolution of the free acid is pH-dependent, the selection of buffered media should be justified by the product’s intended release site. Roller compaction of sulfadimidine base for dry granulation can be performed, but published data for this specific configuration is limited; ribbon density and granule porosity should be established on production-scale equipment because the narrow particle size distribution of micronized API can segregate during die filling.
Sulphadimidine sodium is used in injectable manufacture because the free base cannot produce a therapeutically relevant concentration in aqueous media at physiological pH. The sodium salt is freely soluble in Water for Injections, and the resulting solution is alkaline; pH is adjusted into the acceptable range with dilute hydrochloric acid. In aseptic manufacturing, the API is dissolved in pre-sterilised Water for Injections, passed through a 0.22 µm sterilising-grade membrane filter, and filled under Grade A conditions. For terminally sterilised ampoules, the solution is autoclaved at 121 °C for a defined F0; the stability of the finished solution under autoclaving must be confirmed because sulfadimidine sodium solutions can discolour in the presence of oxygen.
Bacterial endotoxins are tested by Ph.Eur. 2.6.14; the acceptable limit is calculated from the intended maximum parenteral dose and is not a single universal value. Particulate matter in finished injections is checked by Ph.Eur. 2.9.19. Container compatibility studies should include Type I glass ampoules and low-extractable rubber stoppers. If antioxidants such as sodium metabisulfite are used, the addition should be evaluated for pH shift and for any effect on assay by HPLC.
The sodium salt is hygroscopic. During weighing and solution preparation, exposure to ambient moisture above 60% relative humidity should be limited to avoid clumping and inaccurate potency calculation. Nitrogen blanketing of the solution holding vessel is applied when prolonged holding is required to reduce oxidative discolouration.
In comparison with other sulfonamide APIs, sulfadimidine is a short-acting sulfonamide with relatively rapid renal elimination after N4-acetylation. The acetylated metabolite is less soluble in acidic urine than the parent, which creates a crystalluria risk during high-dose oral treatment; this is managed by alkaline diuresis. Sulfamethoxazole is more frequently administered with trimethoprim in human medicine, whereas sulfadimidine is used in a range of veterinary and regional human preparations. Sulfadiazine has a different pyrimidine substitution pattern and a different dissolution and recrystallisation profile; direct substitution is not permitted without bioequivalence and stability data.
The sulfonamide N-H pKa lies close to 7.4, so small changes in urine or solution pH significantly alter the ionised fraction. In injectable formulation this pH sensitivity requires buffering near the target pH before terminal sterilisation. In oral solid dosage forms, the same pH-dependent ionisation affects dissolution in compendial test media and in gastrointestinal compartments. This behaviour differs from sulfamethoxazole formulations that are commonly buffered at higher pH or co-formulated with trimethoprim to broaden antibacterial coverage.
| Property | Base | Sodium salt |
|---|---|---|
| Water solubility | Practically insoluble | Freely soluble |
| Primary dosage route | Tablet, capsule, granule, oral suspension | Injection, concentrated oral solution |
| pH of aqueous dispersion/solution | Near neutral | Alkaline, requires pH adjustment |
| Critical additional control | Particle size, flow, blend uniformity | Bacterial endotoxins, particulate matter, colour stability |
| Typical processing step | Wet granulation or dry blending | Dissolution, 0.22 µm filtration, aseptic fill or autoclave |
The base and sodium salt therefore follow separate validation pathways; a change from one to the other is not a simple mill or sieve change. For oral solid dosage form development, batch-to-batch variance in crystal habit and specific surface area is controlled by X-ray powder diffraction and laser diffraction; changes in these properties across API lots can alter dissolution even when the assay remains within specification. The API user should set incoming particle size and specific surface area ranges in the quality agreement.
The base is stored in well-closed, light-resistant containers at controlled room temperature below 25 °C and protected from moisture. The sodium salt requires resealable containers and is handled under nitrogen where prolonged holding of a prepared solution is required. Sulfadimidine is incompatible with strong oxidising agents and with strongly acidic conditions that may precipitate the free base from sodium salt solutions. Drug-excipient compatibility screening should specifically evaluate aldehyde-containing flavour systems because the primary aromatic amine can participate in condensation reactions. In dry blends, contact with strong mineral acids should be avoided to prevent salt formation that alters dissolution.
