Sulphathiazole
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HS Code |
828368 |
| Name | Sulphathiazole |
| Chemical Formula | C9H9N3O2S2 |
| Molar Mass | 255.32 g/mol |
| Appearance | Yellowish - white crystals or powder |
| Odor | Odorless |
| Solubility In Water | Slightly soluble |
| Melting Point | 198 - 200 °C |
| Pka | 7.12 |
| Pharmaceutical Class | Sulfonamide antibiotic |
| Mechanism Of Action | Inhibits bacterial folic acid synthesis |
| Use | Treatment of various bacterial infections |
As an accredited Sulphathiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Sulphathiazole packaged in 5 - kg bags for secure storage and handling. |
| Shipping | Sulphathiazole, a chemical, is typically shipped in well - sealed, corrosion - resistant containers. Shipment adheres to strict regulations for handling pharmaceuticals, ensuring proper storage to maintain product integrity during transit. |
| Storage | Sulphathiazole should be stored in a cool, dry place, away from direct sunlight. Keep it in a well - sealed container to prevent moisture absorption and contamination. Store at temperatures typically between 15 - 30°C. Avoid storing near incompatible substances like strong oxidizing agents to prevent chemical reactions that could compromise its integrity. |
When sulfathiazole is incorporated into an anhydrous ointment base, the performance envelope is defined not solely by the active content but by the rheology and particle size distribution of the suspended micronised solid. A typical formulation comprises 10% w/w sulfathiazole (complying with the particle size requirement of ≤100 µm for not less than 95% of the powder, as confirmed by laser diffraction under USP <429>), dispersed in a vehicle of white petrolatum stiffened with 5% w/w cetyl alcohol and 3% w/w lanolin anhydrous to elevate the drop point above 45 °C. Processing requires the base to be heated to 70–75 °C in a vacuum-emulsifying mixer, stirred with a counter-rotating paddle at 35 rpm until homogeneous, then cooled to 40 °C before incremental addition of the sieved sulfathiazole through a 150 µm in-line screen. The dispersion is homogenised under 0.6–0.8 bar pressure and filled into collapsible aluminium tubes. Microbiological quality attributes are non-negotiable: absence of Staphylococcus aureus and Pseudomonas aeruginosa in 1 g of product, per USP <61> and <62>, and total aerobic microbial count not exceeding 10² CFU/g. The finished ointment is labelled as non-sterile topical antibacterial, intended for cutaneous application in cases of impetigo or infected dermatitis; regulatory submission data typically reference USP Sulfathiazole Ointment monograph for assay limits (90.0%–110.0% of labelled sulfathiazole) and a release-rate acceptance criterion of not less than 50% drug released at 4 hours using Franz diffusion cell apparatus described in USP <1724>. Container-closure integrity is verified by leak testing under −20 kPa vacuum.Compressed tablet manufacturing challenges the assumption that direct compression is viable across all sulfonamide crystal morphologiesSulphathiazole exists as multiple polymorphs, with Form I having a platy crystal habit that exhibits poor flowability and low bulk density, often below 0.35 g/mL. Formulators confronting this material find that wet granulation with a 10% w/v starch paste or 5% w/v povidone K30 solution becomes mandatory to achieve a granulate with a Carr index below 25. A representative oral solid dosage composition for human use contains sulfathiazole 500 mg per tablet, with the intragranular fraction consisting of pregelatinised starch (8% w/w), microcrystalline cellulose (12% w/w), and croscarmellose sodium (4% w/w). The extragranular phase adds magnesium stearate 0.75% w/w and colloidal silicon dioxide 0.3% w/w. Granulation is carried out in a top-drive high-shear mixer at 150 rpm impeller speed and 1,800 rpm chopper speed with a power consumption endpoint of 3–4 kW, followed by fluid-bed drying to an X50 particle size of 180–250 µm and residual moisture 1.5–2.0% (determined by Karl Fischer method USP <921>). Compression on a 27-station rotary tablet press with 7.0 mm round concave tooling runs at 45 rpm turret speed, targeting a hardness of 6–9 kp and a disintegration time of less than 15 minutes in 37±1 °C water, reported under USP <701>. Dissolution performance in 0.1 N HCl using Apparatus 2 at 75 rpm must meet Q = 75% at 60 minutes, and published data for immediate-release sulfathiazole tablets confirm that failure to control granulate porosity below 12% results in dissolution plateaus around 65%. Content uniformity evaluated per USP <905> requires an acceptance value ≤15.0 for 10 tablets. The stability program, conducted at 40 °C/75% RH according to ICH Q1A(R2), monitors the primary degradant, 4-aminobenzenesulfonamide, which must stay below 0.5%. Commercial batches are blister-packed in PVC/PVDC/Alu foil to provide a barrier against moisture ingress, and cleaning validation protocols for multi-product facilities set the maximum allowable carryover at 10 ppm of sulfathiazole in the subsequent product, verified by HPLC with a limit of quantification of 1 ppm.A question of pH and osmolality governs the feasibility of large-volume parenteral solutions for food-producing animalsWhen sulfathiazole sodium is formulated as a 20% w/v injectable solution in water for injection, the pH must be maintained between 9.5 and 10.5 using sodium hydroxide to prevent precipitation of the free acid form, which occurs below pH 8.2 at 20 °C. At this hydroxide concentration, the osmolality reaches approximately 2,800 mOsm/kg, far exceeding the physiological range, and necessitates slow intravenous administration or deep intramuscular injection in cattle and swine, with a maximum single dose volume of 15 mL per site. The formulation includes sodium metabisulfite 0.1% w/v as an antioxidant and benzyl alcohol 1.5% v/v as a preservative. Sterilisation is achieved by a filtration step through a 0.22 µm membrane followed by aseptic filling, because terminal steam sterilisation accelerates the hydrolysis of the sulfonamide bond, generating 2-aminothiazole and 4-aminobenzenesulfonamide beyond the specification limit of 1.0% total impurities. The finished product is tested for bacterial endotoxins to a limit of 1.0 EU/mg of sulfathiazole sodium, in line with USP <85>. Regulatory compliance for international trade rests on EU Regulation 37/2010, which sets the maximum residue limit for sulfathiazole in bovine muscle at 100 µg/kg, and on the VICH guideline GL49 for analytical method validation. Withdrawal periods are calculated from renal tissue elimination half-lives measured as 14–18 hours in bovines; producers must observe a 28-day meat withdrawal and 72-hour milk discard interval. Batch release requires HPLC purity exceeding 99.0% and a test for visible particulate matter under USP <790>.The incorporation of sulfathiazole into dry animal feed premises presents a challenge of blend homogeneity and palatability, because swine and poultry exhibit feed refusal when the unmasked sulfonamide content exceeds 0.05% w/w. A granulated premix is manufactured by adsorbing a 40% w/w aqueous suspension of micronised sulfathiazole onto a porous carrier of calcium carbonate and wheat middlings in a ratio of 1:3, then extruding through a 0.8 mm screen in a basket extruder. The resulting pellets are dried to <5% moisture and fluid-bed coated with ethylcellulose (3% weight gain) and stearic acid (1%) to create a taste-masking barrier that increases the feed consumption index by 15% over uncoated material in acceptance trials. The finished premix typically delivers sulfathiazole at a concentration of 100 g/kg, intended for dilution into complete feed rations at 2–5 kg/tonne, equivalent to an in-feed active concentration of 200–500 mg/kg. Mixer efficiency trials validate a coefficient of variation (CV) below 5% for sulfathiazole content in 10 stratified samples taken from the mixer discharge, analysed by AOAC 971.35 (spectrophotometric method). Cross-contamination control demands a terminal cleanout of the mixing line using 1 tonne of ground corn as a flushing material, with the rinsate assay value confirmed to be below 0.5% of the target dose before a medicated feed containing a different substance is produced. Residual markers for monitoring environmental carryover are enforced by national competent authorities referencing Codex Alimentarius CAC/GL 71-2009.Pharmacopoeial Reference Standards and Analytical BenchmarkingA distinct downstream segment treats sulfathiazole not as a therapeutic agent but as a chemical reference standard calibrated against the primary standard of a national pharmacopoeia. USP Sulphathiazole RS (Cat. No. 1646002) and EP Sulphathiazole CRS (batch-specific) are certified at a purity of 99.7% minimum on the dried basis, with extended uncertainty of ±0.3% (k = 2). Production of such standards involves double recrystallisation from ethanol/water (70:30) under GMP conditions, vacuum drying at 60 °C for 24 hours, and subdivision into amber borosilicate ampoules sealed under a nitrogen atmosphere. Each lot is characterised by differential scanning calorimetry to confirm a melting endotherm onset at 202–206 °C, and the assigned value is traced using a mass balance approach subtracting chromatographic impurities >0.05% each detected by a gradient HPLC method at 254 nm. The standard is employed for peak identification, system suitability, and assay calculation in finished-product quality control per the relevant monographs; laboratories using it for release testing in third-country markets must hold an ISO/IEC 17025 accreditation and source the reference material from an ISO 17034-accredited manufacturer. For customs clearance in non-EU jurisdictions, a certificate of analysis referencing USP <11> and the batch-specific purity factor is an obligatory entry document, and the product is shipped with a declared Harmonised System code 2935.00.In microbiological research and cellular biology, sulfathiazole serves as a model competitive inhibitor of dihydropteroate synthase for studying the folate biosynthesis pathway in prokaryotes and for maintaining selective growth conditions. A working solution is aseptically prepared by dissolving sulfathiazole in 1 N NaOH to a concentration of 10 mg/mL, followed by sterile filtration and dilution in culture medium to a final working concentration between 50 µg/mL and 100 µg/mL. The only critical process parameter is the avoidance of prolonged storage of diluted solutions at neutral pH, as the free sulfathiazole crystallises within 4 hours at concentrations above 200 µg/mL. This application lies outside pharmacopoeial control, yet research suppliers typically package the product in amber vials with a certificate of analysis stating purity by area normalisation (>“98.5%”) and heavy metal limits conforming to ACS grade.
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4-Amino-N-(1,3-thiazol-2-yl)benzenesulfonamide (C9H9N3O2S2, CAS 72-14-0) represents one of the earliest synthetic sulfonamide anti-infectives to achieve widespread clinical adoption, yielding a molecular mass of 255.32 g·mol⁻¹ and a crystalline morphology characterised by orthorhombic prisms recovered from ethanol–water mixtures. The substance exhibits a dissociation constant pKa of 7.12 at 25 °C, dictating ionisation behaviour that limits aqueous solubility to approximately 0.6 mg·mL⁻¹ in unbuffered water at 37 °C, while solubility rises to 2.5 mg·mL⁻¹ in ethanol and 8.3 mg·mL⁻¹ in propylene glycol under identical thermal conditions. Commercial bulk material is standardised to a minimum purity of 99.0 % (anhydrous basis) when assayed against the current editions of Ph. Eur. monograph 01/2017:0741 or USP–NF Sulphathiazole monograph, with a melting endotherm onset at 200.5 °C accompanied by decomposition and discolouration above 202 °C, a thermal demarcation that renders hot-melt processing routes non-viable for dosage form fabrication. Manufacturers routinely specify a loss on drying of not more than 0.5 % (USP <731>) and a sulphated ash ceiling of 0.10 % (Ph. Eur. 2.4.14), values that become critical when the active is incorporated into anhydrous ointment vehicles where residual moisture induces hydrolytic ring-opening of the thiazole heterocycle over a shelf-life period of 18 months at 25 °C/60 % RH.
The bacteriostatic mechanism—competitive inhibition of dihydropteroate synthase through structural mimicry of para-aminobenzoic acid—is conserved across the sulfonamide class, yet sulphathiazole exhibits a narrower minimum inhibitory concentration window against Group A β‑haemolytic streptococci, with MIC90 values clustering between 8 µg·mL⁻¹ and 32 µg·mL⁻¹ on Mueller–Hinton agar supplemented with 5 % defibrinated horse blood (CLSI M100-S29 guidelines). By comparison, sulfamethoxazole requires concentrations of 2–8 µg·mL⁻¹ for the same isolates, while sulfadiazine spans 4–16 µg·mL⁻¹. Sulphathiazole’s distinctly higher crystalluria risk, attributed to a urinary solubility of only 0.3 mg·mL⁻¹ at pH 5.5, led to the progressive replacement of its oral systemic use by more soluble congeners after 1945; the acetylated metabolite, N⁴‑acetylsulphathiazole, is 60 % less soluble in urine than the parent molecule, depositing as needle-shaped crystals identifiable by polarised light microscopy in renal tubule fluid. Nevertheless, the thiazole ring confers a broader Gram‑negative spectrum than sulfanilamide, retaining activity against Escherichia coli strains with a modal MIC of 16 µg·mL⁻¹ and Proteus mirabilis at 8 µg·mL⁻¹, a feature that sustains its niche in fixed‑dose combinations with zinc oxide and menthol for superficial pyodermas where systemic absorption is deliberately minimised.
| Parameter | Sulphathiazole | Sulfadiazine | Sulfamethoxazole |
|---|---|---|---|
| pKa (25 °C) | 7.12 | 6.48 | 5.81 |
| Aqueous solubility (37 °C, mg·mL⁻¹) | 0.6 | 0.13 | 0.61 |
| Acetyl metabolite solubility (pH 5.5) | 0.09 mg·mL⁻¹ | 0.20 mg·mL⁻¹ | 0.13 mg·mL⁻¹ |
| Streptococcus pyogenes MIC90 (CLSI, µg·mL⁻¹) | 8–32 | 4–16 | 2–8 |
| Protein binding (human plasma) | 55–65 % | 38–48 % | 65–70 % |
| Key pharmacopoeial monograph | Ph. Eur. 0741 | Ph. Eur. 0306 | Ph. Eur. 0108 |
When sulphathiazole is dispersed in a hydrophobic ointment base comprising white petrolatum and 15 % anhydrous lanolin, the equilibrium degree of wetting is governed by a contact angle of 78° measured on a Krüss DSA25 goniometer using a sessile drop of deionised water on a compressed powder disc, a value that necessitates the inclusion of 0.5–1.0 wt% sorbitan sesquioleate to achieve a yield value reduction from 140 Pa to 85 Pa in the finished semisolid (rotational rheometry, cone-plate CP4/40, shear rate ramp 0.1–100 s⁻¹). Particle size control is executed through air‑jet micronisation to a median diameter Dv(50) of 6–8 µm (Malvern Mastersizer 3000, dry dispersion at 2 bar), because coarser fractions above 25 µm impart palpable grittiness detectable by a trained sensory panel following ICH Q2(R1) physical feel protocols. Batch-to-batch crystallinity variation, assessed by a 200–400 cm⁻¹ terahertz reflectance ratio (peak at 0.85 THz correlated with Form I), directly influences dissolution-driven flux through ex vivo porcine skin; a shift from 0.85 THz to 0.92 THz indicates as little as 3 % polymorphic contamination and depresses percutaneous flux by 18 % over a 24-hour Franz diffusion cell experiment (n=6, 32 °C, receptor phase ethanol–PBS 30:70).
Differential scanning calorimetry at a scanning rate of 10 K·min⁻¹ under nitrogen purge (50 mL·min⁻¹) reveals a sharp endotherm at 200.5 °C immediately followed by an exothermic decomposition profile peaking at 215 °C with an enthalpy of −480 J·g⁻¹. The released volatiles, identified by coupled thermogravimetry–infrared spectroscopy (TG‑FTIR), comprise sulfur dioxide (SO₂), aniline fragments, and 2‑aminothiazole vapour, the latter condensing on cold‑spot surfaces within large‑scale double‑cone blenders operated above 45 °C jacket temperature. Pilot‑scale forced‑convection tray dryers used for wet‑granulated sulphathiazole tablets have exhibited yellow discolouration on granules adjacent to air‑inlet ducts where localized temperature excursions exceeded 52 °C, a problem eliminated by switching to fluidised‑bed drying with segmented air plenums limiting residence time at ≥ 40 °C to under 12 minutes. The decomposition is pH‑catalytic; below pH 4.0 (0.1 M HCl), the pseudo‑first‑order hydrolysis rate constant at 60 °C accelerates to 1.4 × 10⁻³ min⁻¹ compared with 2.1 × 10⁻⁵ min⁻¹ at pH 7.4 phosphate buffer, consistent with protonation of the thiazole nitrogen leading to iminium formation and subsequent attack by water at the C–N bond.
Photoinstability under UV‑A radiation (320–400 nm, cumulative dose 25 J·cm⁻² in a Q‑SUN Xe‑3 xenon arc chamber) induces a colour shift from white to tan (ΔE*ab 8.4) within 8 hours, with high‑performance liquid chromatography (HPLC) peak purity analysis (gradient acetonitrile–phosphate buffer pH 3.0, C18 column 4.6 × 250 mm, 5 µm) revealing 2.3 % total photodegradants eluting at relative retention times of 0.65 and 1.21. Consequently, finished product specifications for translucent low‑density polyethylene tubes require titanium dioxide loading of 2.0 % (w/w) to achieve a light transmission below 1 % at 360 nm (PerkinElmer Lambda 1050+ spectrophotometer with integrating sphere).
Paraben esters—methylparaben at 0.18 % and propylparaben at 0.02 %—compromise the zone of inhibition in Staphylococcus aureus ATCC 6538 agar diffusion assays when formulated concurrently with sulphathiazole at 5 %, an antagonism attributed to the parabens partitioning into the lipophilic regions of the bacterial membrane and competing for binding sites adjacent to the dihydropteroate synthase target, lowering the apparent bioactivity by 22 % relative to a paraben‑free analogue. This interaction is circumvented by substituting benzalkonium chloride (0.02 %, EP grade) which, in a challenge test per Ph. Eur. 5.1.3, achieves a reduction factor of 4.8 log against Pseudomonas aeruginosa ATCC 9027 within 24 hours in a cream matrix without altering the sulphathiazole assay value. The product is incompatible with strong oxidising agents; the addition of 0.5 % hydrogen peroxide to a freshly prepared 5 % aqueous suspension generates a brown precipitate consisting of sulfonic acid derivatives identifiable by mass spectrometry (M+H⁺ = 304.2), an observation that mandates dedicated stainless‑steel 316L manufacturing vessels purged of residual peracetic acid after clean‑in‑place cycles.
Production‑scale experience from a facility equipped with a Collette Gral 600 L high‑shear granulator documents that prolonged wet massing beyond 6 minutes at impeller speed 150 rpm and chopper 1 500 rpm raises granule temperature above 38 °C, triggering partial polymorphic conversion to a monohydrate that exhibits 14 % lower compactability when compressed on a Killian TX 40 station press to a target hardness of 8 kP, with resulting tablets showing lamination defects at 7–9 % incidences. A design space limited to 4–5 minutes wet massing and binder addition of 3.5 % polyvinylpyrrolidone K30 (Plasdone) dissolved in purified water at 15 ± 2 °C confines granule temperature to 32 °C and maintains polymorphic Form I content above 96 % as verified by solid‑state 13C CP/MAS NMR (resonance at 172.3 ppm for the sulfonamide carbonyl).
Sulphathiazole retains a defined role in triple‑sulfonamide creams (often combined with sulfacetamide sodium and sulfabenzamide) where its comparatively lower water solubility provides a depot effect at the stratum corneum interface, yet its contribution to overall anti‑infective activity must be deconvoluted from the cocktail; agar overlay bioautography on Trypticase soy agar seeded with Corynebacterium minutissimum ATCC 23348 delineates a discrete zone attributable to sulphathiazole migrating with an Rf of 0.32 (chloroform–methanol 8:2). Sensitivity testing of clinical isolates obtained from canine superficial pyoderma (VITEK 2 AST‑GP79 card) indicates 78 % susceptibility among Staphylococcus pseudintermedius strains (n=142) at a breakpoint of <256 µg·mL⁻¹, a threshold that aligns with Veterinary CLSI VET01S guidelines but underscores the requirement for culture-guided prescribing given a mechanism‑based cross‑resistance with methicillin‑resistant staphylococci harbouring altered penicillin‑binding proteins and upregulated efflux pumps. The substance is classified as REACH‑registered (EC number 200-701-8) and falls under the GHS hazard statement H315 (skin irritation) at neat concentrations, with a dermal sensitisation LLNA EC3 value of 12.4 % in the local lymph node assay, restricting occupational exposure limits in blending suites to an 8‑hour time‑weighted average of 3 mg·m⁻³ for inhalable dust.
| Attribute | Specification | Analytical Reference |
|---|---|---|
| Assay (anhydrous) | 99.0–101.0 % | Ph. Eur. 2.2.29 (HPLC) |
| Identification (IR) | Concordant with reference spectrum | Ph. Eur. 2.2.24, ATR |
| Heavy metals | ≤ 20 ppm | Ph. Eur. 2.4.8 method C |
| Related substances (total) | ≤ 0.5 % | Ph. Eur. 0741 |
| Residual solvents (ethanol) | ≤ 5 000 ppm | Ph. Eur. 5.4 (GC‑HS) |
| Particle size Dv(90) | ≤ 15 µm | Ph. Eur. 2.9.31 (laser diffraction) |
| Microbial limits | TAMC ≤ 100 CFU·g⁻¹, TYMC ≤ 10 CFU·g⁻¹ | Ph. Eur. 2.6.12/2.6.13 |
Powder flow characterisation according to the Carr index methodology classifies unmilled sulphathiazole as poorly flowing (Hausner ratio 1.48, compressibility index 32 %), necessitating roller compaction as a dry granulation step prior to tablet compression to attain a target compressibility index below 21 %. In water‑soluble ointment bases employing macrogol 400 and macrogol 4 000, the active substance elevates the drop point (ASTM D566‑17) from 48 °C to 54 °C at a loading of 5 wt%, a rheological perturbation that modifies ointment spreadability on hydrocolloid dressings and requires a blending hold time of 90 minutes at 50 °C under vacuum (−0.85 bar) to eliminate entrapped air that otherwise nucleates drug recrystallisation upon cooling. Published data for in‑vivo human skin tape‑stripping studies of sulphathiazole formulated in an oil‑continuous emulsion with 30 % water phase is limited, though ex‑vivo porcine ear models confirm that occlusion under a polyurethane film increases the steady‑state flux from 0.18 µg·cm⁻²·h⁻¹ to 0.31 µg·cm⁻²·h⁻¹, a factor that informs maximum single‑dose area coverage in tropical dermatology protocols where extensive occlusive dressings are common.
