| HS Code | 471235 |
| Product Name | Ceftizoxime Sodium (Sterile) Pharma Grade API |
| Chemical Name | (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid sodium salt |
| Cas Number | 68401-81-0 |
| Molecular Formula | C13H12N5NaO5S2 |
| Molecular Weight | 405.38 g/mol |
| Appearance | White to pale yellow crystalline powder |
| Solubility | Freely soluble in water; slightly soluble in methanol; practically insoluble in most organic solvents |
| Sterility | Sterile, pyrogen-free, and suitable for aseptic pharmaceutical processing |
| Pharmaceutical Grade | High-purity active pharmaceutical ingredient (API) meeting pharmacopoeial standards |
| Storage | Protect from light, moisture, and heat; store below 25°C in an airtight original container |
| Intended Dosage Forms | Tablet, capsule, granule, and sterile injectable formulations for oral and parenteral routes |
| Pharmacological Class | Third-generation cephalosporin antibiotic |
| Mechanism Of Action | Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to bactericidal activity |
As an accredited Ceftizoxime Sodium (sterile) 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 | Sterile Ceftizoxime Sodium API packed in sealed double polythene bags with aluminum foil, 25 kg per drum, suitable for oral and injectable dosage forms. |
| Container Loading (20′ FCL) | 20′ FCL loading of sterile Ceftizoxime Sodium API in sealed drums, palletized and secured, ensures safe transport for oral/injectable pharmaceutical use. |
| Shipping | This sterile Ceftizoxime Sodium API is shipped in temperature-controlled containers (20–25°C), protected from light and moisture. Packed in sealed double polyethylene bags with desiccants inside tamper-evident drums, it includes full batch documentation and safety data, ensuring GMP-compliant, secure handling for all pharmaceutical formulations. |
| Storage | Store in sterile, tightly sealed, light-resistant containers in a cool, dry place below 25°C. Protect from moisture, heat, and direct sunlight. For sterile Pharma Grade API, maintain integrity of the container and avoid contamination. Use immediately after opening; if repacking is necessary, perform under aseptic conditions. |
| Shelf Life | Shelf life is 24 months from manufacture date when stored in original container under recommended temperature, protected from moisture and light. |
Aseptic powder filling lines hold bulk density and crystal habit as primary variables; ceftizoxime sodium is filled as a neat powder on such lines only when both are controlled. Most sterile ceftizoxime sodium batches are white to pale yellow crystalline solids obtained by solvent precipitation and vacuum drying; the particle size distribution is often controlled at d10 ≥ 10 µm, d50 45–180 µm, and d90 ≤ 500 µm to balance reconstitution time against powder flow. Powders in this range, especially those with needle-like or plate-shaped crystal habits, can exhibit angle of repose values above 40°, Hausner ratios above 1.25 when bulk and tapped density are measured per USP <616>, and flow function coefficients below 5 when tested by shear cell in accordance with ASTM D6773. Volumetric auger and vacuum-drum filling equipment operating under ISO 14644-1 Grade A conditions must therefore be mapped for fill weight drift when bulk density shifts by as little as 0.05 g/mL. A 1 g vial fill weight acceptance of ±2% is routinely monitored by in-line checkweighers and offline USP <905> uniformity testing; sustained drift above this zone triggers fill depth adjustment and hopper refill validation. In-process temperature and relative humidity are held at 18–22°C and 20–40% RH because the sodium salt is hygroscopic enough to change water activity on open exposure; electrostatic adhesion to 316L electropolished stainless steel and polymer contact surfaces becomes the dominant yield-loss mechanism below 30% RH. Aseptic filling operations for this product are governed by 21 CFR 211.113(b), and media fill simulation must support a contamination rate below 0.1% at the 95% confidence interval per ISO 13408-1.
Residual water in sterile ceftizoxime sodium powder acts as a reaction medium for β-lactam ring opening. Karl Fischer titration per USP <921> Method Ia is generally used for certifying moisture in the sterile API; the assigned release limit must be derived from ICH Q1A stability data rather than from a fixed compendial tolerance. When exposed to room air at 60–70% RH, the powder surface can adsorb sufficient moisture within 10–15 min to raise water content by 0.2–0.5% w/w, depending on crystal surface area and amorphous content. Amorphous domains generated by excessive micronization or high-shear wet granulation are particularly reactive because they lack the lattice energy barriers of crystalline drug substance; even a small amorphous fraction can produce a lowering of the glass transition temperature of the wet mass and accelerate solid-state degradation. Dry powder filling lines therefore avoid wet granulation, fluid-bed drying, or terminal steam sterilization. Humidity monitoring inside the hopper and under the filling head is recorded continuously; excursions above 40% RH trigger batch segregation and retesting for moisture, assay, and related substances. Dissolution of the filled powder during reconstitution is also affected by particle size and moist agglomeration; if the powder forms cakes from moisture uptake, reconstitution time with Sterile Water for Injection can increase to more than 2 min and produce visible particulates that fail USP <790>.
Autoclaving at 121°C for 15 min is not used for sterile ceftizoxime sodium because aqueous hydrolysis of the β-lactam ring proceeds rapidly at neutral-to-alkaline pH; dry-heat depyrogenation above 160°C introduces discoloration and assay loss. Instead, the sterile API is obtained by aseptic crystallization from a solution that has been passed through a sterilizing-grade 0.2 µm filter. Filter integrity testing must be performed before and after filtration by bubble point or diffusion flow according to the filter manufacturer’s validated values; post-use integrity failure invalidates the batch. Aseptic solvent precipitation, washing, and vacuum drying are carried out in closed systems under Grade A air or isolated conditions; any transfer into the fill line uses alpha-beta ports or rapid transfer ports that have been validated for surface decontamination. Environmental monitoring at the crystal drying and discharge points includes active air sampling, settle plates, contact plates, and particle counting under ISO 14644-1; the microbiological alert and action limits are based on historical data and PIC/S recommended limits. Since the drug substance is a sterile cephalosporin, bioburden reduction before filtration is controlled to a maximum pre-filtration count of 10 CFU/100 mL; this is a common starting point for aseptic filtration validation, though the exact limit must be justified by process capability. The absence of terminal sterilization places the entire batch acceptance on sterile API release testing: USP <71> sterility, USP <85> bacterial endotoxins, and USP <788>/<790> particulate matter. Each lot is also evaluated for identity and assay by HPLC using the official ceftizoxime sodium monograph conditions; retention time and resolution requirements must be met with the working standard lot.
The choice of infusion diluent changes the hydrolytic exposure window. Ceftizoxime sodium reconstituted with Sterile Water for Injection typically yields a solution with pH in the 6.0–8.0 range; this is the region of maximum stability for the β-lactam core. Transfer into 5% Dextrose Injection shifts the admixture toward the acidic range because dextrose solutions carry a pH specification commonly between 3.2 and 6.5. In this lower-pH environment, the rate of β-lactam ring opening increases; the magnitude depends on final drug concentration, storage temperature, and the actual measured pH of the admixture. Pharmacy compounding of intravenous solutions must therefore record the diluent lot pH and control hold time at 2–8°C where extended storage is required. 0.9% Sodium Chloride Injection has a pH nearer neutrality and is generally preferred when the infusion will hang for more than 6 h at room temperature. Visual inspection before administration is mandatory under USP <790>; any haze, precipitation, or color change indicates chemical degradation or incompatibility. Aminoglycoside antibiotics must not be mixed with ceftizoxime sodium in the same container or Y-site line because β-lactams can chemically inactivate aminoglycosides in vitro; separate infusion access or adequate flushing is required. The final admixture concentration is usually selected within the range of 10–40 mg/mL for intermittent IV infusion, but the upper limit is dictated by solubility and osmolality rather than by a fixed pharmacopeial requirement.
Compounding sterile ceftizoxime sodium into conventional oral tablets, capsules, or dry granules does not overcome the molecule’s poor oral drugability. The free carboxylate group and the ionized sodium salt produce low passive permeability across the intestinal epithelium, while the β-lactam ring undergoes acid-catalyzed hydrolysis at gastric pH 1.2. Published data for the oral bioavailability of ceftizoxime sodium are limited; no USP-NF tablet, capsule, or oral granule monograph exists for this compound. A direct compression tablet would require dry binder, disintegrant, and lubricant, but the formulation process itself—especially wet granulation—can introduce heat and moisture that accelerate lactam degradation. Enteric coating of multiparticulates could in theory protect the drug from gastric acid, but protection from gastric acid does not create adequate permeability; the carboxylate would still hinder passive diffusion across the ileal and colonic mucosa. Moreover, the high aqueous solubility of the sodium salt means a coated multiparticulate could burst-release in the small intestine and produce local high osmolarity with uncertain absorption. For oral cephalosporin therapy, marketed options rely on ester prodrugs with lipophilic side chains that increase intestinal uptake; ceftizoxime sodium is not supplied in such a prodrug form. Repurposing the sterile injectable API for oral granule filling is therefore not supported by pharmaceutical development data and would fail the bioavailability-based claim requirements of 21 CFR 320 unless a complete clinical bridging program was conducted.
Because β-lactam sensitization is a serious immunologic risk, the facility segregation decision for ceftizoxime sodium begins with containment engineering rather than only cleaning. In a facility that handles this sterile API, all product-contact surfaces, air handling, and personnel flow must be designed to prevent carryover of cephalosporin residues into other products. Dedicated suites with single-pass air and negative pressure are standard for cephalosporin powder processing; in contrast to penicillin, the regulatory expectation for non-penicillin β-lactams is risk-based, but most sites apply the same containment philosophy. Cleaning validation uses swab and rinse samples analyzed by a stability-indicating HPLC method capable of quantifying ceftizoxime sodium above a limit of quantification of 0.02 µg/swab to 0.1 µg/swab, depending on instrument sensitivity. Acceptance limits are calculated from the maximum allowable carryover of 10 mg/kg to the next product, the daily dose of the next product, and the batch size; the resulting swab limit is often below 1 µg/25 cm². Equipment train design should include polished 316L stainless steel with Ra finish not exceeding 0.8 µm, minimal threaded connections, and dismantling of rotary valves, vacuum lines, and filter housings before cleaning. In addition to visual cleanliness, rinse water samples should be checked for conductivity and total organic carbon per USP <643>. Personnel protection typically requires isolators, split-butterfly valves, and validated garment change procedures because dry powder can become aerosolized during docking and discharge. A documented matrix of product changeover, including the maximum time dirty equipment is held before cleaning, must be maintained under 21 CFR 211.67(b).
For vials sealed with Type I borosilicate glass and halogenobutyl elastomer closures, container closure integrity testing must detect leaks that could admit microorganisms, moisture, or oxygen during shelf life. USP <1207> classifies CCI methods as deterministic or probabilistic; vacuum decay, laser-based headspace oxygen analysis, and pressure decay are preferred because they generate quantitative pass/fail limits. The method selected should be qualified with positive controls using glass micropipettes or laser-drilled defects in the range of 2–10 µm; detection probability above 95% at the chosen defect size is expected. Dye ingress tests are simple but lower in sensitivity and are best used for initial package selection rather than release testing. Moisture ingress is a critical variable for ceftizoxime sodium because even small increases in vial water activity can shorten the retest period; headspace moisture analysis or near-infrared spectroscopy may be used on stability to track this parameter. The capping process must be validated for residual seal force—values in the range of 20–40 N for 13 mm elastomer closures are often cited in packaging engineering literature, though equipment-specific values must be established by compression set studies. Every lot should be checked for visual closure defects, loose caps, and cracked glass before labeling; 100% in-line optical inspection is increasingly used for high-speed parenteral lines. Storage stability testing follows ICH Q1A at 25°C/60% RH long-term and 40°C/75% RH accelerated conditions; water content, assay, related substances, sterility, and pH of reconstituted solution are the stability-indicating parameters.
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Ceftizoxime Sodium (sterile) Pharma Grade API is supplied as a sterile crystalline or lyophilized sodium salt with molecular formula C13H12N5NaO5S2, CAS registry number 68401-81-0, and relative molecular mass 405.4 g/mol. The material is specified against the current USP monograph for Ceftizoxime Sodium, with corresponding pharmacopoeial alignment to Ph. Eur. and JP where a monograph exists. The term “model” is not a pharmacopoeial identifier; procurement specifications use the monograph name, salt form, sterility grade, and manufacturer material code. In finished-dosage manufacturing, the API is intended primarily for sterile injectable preparations, including dry powder for reconstitution, lyophilized injection, and bulk solution admixtures. Although the task specification lists tablet, capsule, and granule applications, the oral route is constrained because ceftizoxime sodium exhibits β-lactam susceptibility to gastric acid and limited oral bioavailability; published data for this specific oral configuration is limited. An unmodified oral solid dosage form is therefore not typically manufacturable from the sterile sodium salt, and alternative oral cephalosporins are preferred unless a validated enteric delivery platform is used. Primary packaging for the API normally comprises a low-density polyethylene inner liner inside an aluminium laminate barrier with a desiccant sachet; the product is not intended for direct administration without validated reconstitution or filtration.
The sodium salt is a third-generation cephalosporin carrying a 2-aminothiazolyl methoxyimino side chain. This side chain contributes to resistance against certain gram-negative β-lactamases, but it does not confer universal β-lactamase stability. The sterile grade is manufactured from a depyrogenated solution by aseptic crystallization or lyophilization, followed by aseptic micromilling and packaging under ICH Q7 conditions. Release potency is expressed on an anhydrous, solvent-free basis; the fill weight of a finished injectable is calculated from the batch assay result.
Release of sterile ceftizoxime sodium is controlled by compendial sterility testing according to USP <71>, bacterial endotoxins according to USP <85>, and sub-visible particulate matter according to USP <788> for the finished injectable. The API is processed in an aseptic environment meeting ISO 14644-1:2015 Class 5 or better under EU GMP Annex 1, with depyrogenation of contact equipment by dry heat at 250 °C for not less than 30 min or an equivalent validated cycle. Production-scale sterile dry-powder filling uses barrier isolation or restricted-access barrier systems to close critical Grade A zones; terminal moist-heat sterilization is generally unsuitable because cephalosporin sodium salts undergo β-lactam ring opening at elevated temperatures. Equipment cleaning and sanitization are performed in accordance with FDA 21 CFR 211.67; stainless-steel contact parts are passivated and dried before use.
| Release Attribute | Standard Reference | Technical Purpose |
|---|---|---|
| Sterility | USP <71>; Ph. Eur. 2.6.1 | Confirms absence of viable microorganisms in the aseptically processed API |
| Bacterial endotoxins | USP <85>; Ph. Eur. 2.6.14 | Limits pyrogen burden for parenteral administration |
| Sub-visible particulate matter | USP <788>; Ph. Eur. 2.9.19 | Controls particulate load after reconstitution |
| Water content | USP <921>; Ph. Eur. 2.5.12 | Prevents hydrolysis and flow deterioration |
| Residual solvents | USP <467>; Ph. Eur. 5.4 | Limits solvent-derived impurities from crystallization |
| Assay by HPLC | USP Ceftizoxime Sodium monograph | Quantifies anhydrous, solvent-free potency |
| pH after reconstitution | USP <791>; Ph. Eur. 2.2.3 | Controls solubility and injection-site compatibility |
| Particle-size distribution | ISO 13320:2020 | Controls reconstitution time and fill-weight uniformity |
Environmental monitoring during aseptic processing includes settle plates, active air sampling, and contact plates; Grade A active air action limits are set at 1 CFU/m³ under EU GMP Annex 1. Personnel gowning, training, and aseptic technique are qualified before campaign start and requalified at least annually. Growth promotion of sterility media includes Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, and Aspergillus brasiliensis; test validity is assessed according to USP <71>. Endotoxin limits are product-specific and expressed in EU/mg; they are derived from the maximum bolus dose per kilogram and the patient population specified in the marketing authorization.
Batch-to-batch variance in residual water content is monitored by Karl Fischer titration following USP <921>, and residual solvents are controlled under USP <467> for solvent-derived impurities. Failure modes observed on actual transfer lines include electrostatic adhesion of micronized powder to isolator gloves and non-laminar pockets in split butterfly valves; these are mitigated by room relative humidity control in the range 20–40% and use of conductive flooring. In lyophilized injection manufacturing, bulk solution is sterile-filtered through 0.22 µm PVDF or polyethersulfone membranes, filled into vials, and freeze-dried. The lyophilization cycle is developed with controlled shelf-temperature ramp rates and chamber pressure; collapse of the cake occurs if the product temperature exceeds the collapse temperature during primary drying. Residual moisture after freeze-drying is verified by Karl Fischer and must remain below the dossier-specified limit. Filter integrity is tested by bubble point, diffusive flow, or water intrusion before and after use; test methods follow manufacturer technical bulletins and ASTM F838-20 or equivalent. Depyrogenation tunnel validation includes endotoxin challenge vials containing not less than 1000 EU per vial; the required temperature and belt speed are established to achieve not less than 3 log reduction.
For dry-powder injection presentation, ceftizoxime sodium is controlled-crystallized or micronized to suit high-speed filling. Particle-size distribution is measured by laser diffraction according to ISO 13320:2020; tapped bulk density and flow character are assessed by USP <616> and USP <1174>. High-shear milling is limited because local frictional heating can generate amorphous domains, increasing hygroscopicity and reducing chemical stability. On rotary filling machines, powder bridging or segregation can produce fill-weight variation outside ±5% of target; conditioned stainless-steel hoppers and low-vibration transfer lines are used. Micronization with nitrogen-cooled opposed-jet mills reduces thermal stress; the milled powder may be conditioned in a double-cone blender under controlled humidity. Bulk density is measured by USP <616>; Hausner ratio and Carr index are calculated as flow descriptors, with a Hausner ratio below 1.25 and a Carr index below 25 generally indicating passable flow for rotary fillers. Electrostatic charge is measured by Faraday pail; antistatic additives are not allowed in a sterile injectable API, so humidity and equipment grounding are the primary controls.
Reconstitution time in sterile water for injection is measured under controlled vortex mixing; the sodium salt is freely soluble, yielding a clear to slightly straw-coloured solution. pH is determined after reconstitution by USP <791> using a calibrated pH meter. No universal pH acceptance criterion applies to the API alone; finished-product pH is fixed in the marketing-authorization dossier. In lyophilized presentations, cake density and residual moisture influence reconstitution; porous cakes with low residual moisture reconstitute faster than dense or collapsed cakes, and fill-line operators should reject vials with visible cake defects. Powder flow in dosator or vacuum-drum filling systems is further influenced by bulk density and particle-size distribution; in-process fill-weight checks are performed at defined intervals and monitored by statistical process control.
Direct compression of unmodified sterile ceftizoxime sodium into tablets or capsules without enteric coating is unlikely to provide reliable systemic delivery because the β-lactam carbonyl is acid-labile in the fasting stomach and the sodium salt is hygroscopic. Granule formulations intended for extemporaneous oral suspension would require buffering agents, desiccant packaging, and possibly a taste-masking layer; however, published data for this specific configuration is limited, and regulatory precedent favours alternative oral cephalosporins such as cefixime or cephalexin for oral solid dosage forms. If an oral granule blend is processed, the granulation equipment should be dedicated to β-lactam production to prevent cross-contamination and must be validated for cleaning per FDA 21 CFR 211.67. Enteric coating of the sodium salt would require organic-solvent or aqueous barrier coating; the high aqueous solubility of the salt can cause migration into the subcoat during spraying, and no pharmacopoeial dissolution monograph exists for ceftizoxime sodium oral tablets. Any development batch intended for oral use would require dissolution testing per USP <711> against an internally validated method, but published data for this product configuration is limited.
In third-generation cephalosporin portfolios, ceftizoxime sodium differs from cefotaxime sodium by the absence of the C-3 acetoxymethyl substituent; this reduces ester hydrolysis and desacetyl metabolite formation in the finished preparation. Ceftazidime pentahydrate carries a pyridine-based C-3 substituent and is selected for anti-pseudomonal coverage, whereas ceftizoxime sodium is not typically designated for Pseudomonas aeruginosa coverage. The sodium load per 1 g of ceftizoxime sodium is 56.7 mg of sodium; this is a formulation constraint in sodium-restricted patient populations. Compared with ceftriaxone disodium, ceftizoxime sodium has lower protein binding and a shorter elimination half-life; the clinical dosing interval is generally shorter. The sterile API is stored in sealed low-permeability containers at 2–8 °C; excursions above 25 °C should be minimized because moisture ingress accelerates β-lactam hydrolysis. The sodium salt should not be combined with strong oxidizing agents or alkaline buffer salts during bulk solution preparation; concentrated acidic diluents may also cause precipitation or rapid degradation. Ceftazidime pentahydrate is not a direct sodium salt and requires sodium carbonate for reconstitution, whereas ceftizoxime sodium is a direct sodium salt; this difference influences compounding workflows in hospital pharmacy and outsourced admixture units.
| Product | CAS Registry Number | Molecular Formula | Sodium Content per Gram | Typical Finished Form |
|---|---|---|---|---|
| Ceftizoxime sodium | 68401-81-0 | C13H12N5NaO5S2 | 56.7 mg/g | Sterile dry powder or lyophilised injection |
| Cefotaxime sodium | 64485-93-4 | C16H16N5NaO7S2 | 48.2 mg/g | Sterile dry powder injection |
| Ceftazidime pentahydrate | 78439-06-2 | C22H32N6O12S2 | 0 mg/g as pentahydrate; sodium carbonate is added for solution | Sterile dry powder or solution for injection |
Process capability comparisons across cephalosporin sodium salts show different drying and crystallisation behaviour due to variations in hydrate form. Published solid-state data for ceftizoxime sodium hydrate is limited; storage and handling must therefore be controlled by sealed container integrity and moisture vapour transmission rate rather than assumed hydrate stoichiometry. Residual solvent profiles also differ: cefotaxime sodium and ceftazidime pentahydrate may carry different crystallisation solvents; ceftizoxime sodium API must meet the same USP <467> residual solvent criteria, but the specific solvent list is dossier-defined. The sterile API is not interchangeable with ceftriaxone sodium on a gram-for-gram basis in compounding, because the molecular structures, sodium loads, plasma protein binding, and elimination half-lives differ. Formulators preparing a bulk solution for intravenous infusion must use the specific potency and density data for ceftizoxime sodium; published density data for bulk crystalline powder is product-specific. The material should not be blended with other cephalosporin sodium salts in a single vial.
Stability studies for sterile ceftizoxime sodium use storage conditions defined by ICH Q1A(R2) for climatic zones I–IV; long-term storage at 25 °C/60% RH and accelerated storage at 40 °C/75% RH are used only for unopened commercial containers in development. Because the sterile API is hygroscopic, re-sealing of partially used containers is not recommended. Container closure integrity of the sterile API is verified by vacuum decay or helium leak methods according to USP <1207>. Analysis of batch release data from continuous production typically identifies water content and assay as the most sensitive quality attributes; process capability indices above 1.33 are maintained for these attributes in routine manufacture. Cleaned equipment is verified for residual cephalosporin allergens by validated swab and rinse sampling according to FDA 21 CFR 211.67 and applicable occupational exposure limits.
