| HS Code | 925651 |
| Product Name | Tetrabasic Zinc Chloride (TBZC) Pharma Grade API |
| Synonyms | Zinc chloride hydroxide; Zinc hydroxychloride; Basic zinc chloride |
| Chemical Formula | Zn5(OH)8Cl2 |
| Molecular Weight | 533.85 g/mol |
| Cas Number | 10105-20-1 |
| Zinc Content | 61.2% (anhydrous basis) |
| Appearance | White to off-white crystalline powder |
| Odor | Odorless |
| Solubility | Practically insoluble in water; soluble in dilute mineral acids |
| Assay | ≥ 99.0% |
| Grade | Pharma Grade API |
| Dosage Forms | Tablet, Capsule, Granule, Injection |
| Route Of Administration | Oral, Injectable |
| Therapeutic Category | Zinc supplement; trace element |
| Heavy Metals | ≤ 10 ppm |
| Loss On Drying | ≤ 1.0% |
| Particle Size | Typical 80-200 mesh or as specified |
| Storage Conditions | Store in a cool, dry place in a tightly closed container; protect from moisture |
| Packaging | 25 kg fiber drum or foil-lined bag, or as per customer requirement |
| Shelf Life | 24 months when stored properly |
| Regulatory Standard | Complies with USP/EP/BP as applicable |
As an accredited Tetrabasic Zinc Chloride (TBZC) 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 | |
| Shipping | |
| Storage |
Direct compression of tetrabasic zinc chloride monohydrate (Zn5(OH)8Cl2·H2O, theoretical zinc content 59.2% w/w) is assessed against the flow and compaction limitations imposed by direct-compression filler systems. The addition ratio is stoichiometrically fixed: a 25 mg elemental zinc target per tablet requires 42.2 mg TBZC, and a 50 mg target requires 84.4 mg. In a 500 mg core, these inputs correspond to 8.4% w/w and 16.9% w/w respectively; in a 250 mg core, the TBZC fraction rises to 16.9% w/w and 33.8% w/w, and direct compression becomes unstable if the Carr index exceeds 25 or the Hausner ratio exceeds 1.35 when measured according to USP <1174>. The process is run on a rotary tablet press with B-tooling, main compression force 12–18 kN, precompression force 6–9 kN, turret speed 25–45 rpm, and dwell time 5–20 ms; capping and lamination are controlled by keeping the blend loss on drying below 1.5% w/w and replacing sodium croscarmellose with crospovidone at 2.0–4.0% w/w when TBZC exceeds 15% w/w. The terminal product forms are uncoated, film-coated, and sugar-coated tablets. Compliance is governed by 21 CFR 210/211, ICH Q3D elemental impurity risk assessment, USP <905>, USP <711> in 0.1 N hydrochloric acid at 37 °C and 50 rpm paddle, and Ph. Eur. 2.9.40.
Dry granulation is required when direct compression is prohibited by segregation risk because TBZC particles have a higher true density than common direct-compression fillers, producing content uniformity drift across batches longer than 200,000 units. The granulation line consists of a loss-in-weight feeder discharging into an Alexanderwerk WP120 Pharma roller compactor with knurled rolls, roll gap 1.2–2.0 mm, specific compaction force 5–12 kN/cm, roll speed 4–10 rpm, and a screen mill with 0.8 mm rasping screen at 100–150 rpm. In a hard gelatin capsule formula delivering 25 mg elemental zinc, TBZC is incorporated at 37.5% w/w of the granulate; the fill weight is approximately 112.5 mg for a size 1 capsule, containing 42.2 mg TBZC plus mannitol, pregelatinized starch, and sodium stearyl fumarate. If the TBZC fraction exceeds 45% w/w, granule hardness increases above 12 N and disintegration exceeds the 15 min limit for uncoated capsules under Ph. Eur. 2.9.1 and USP <701>; crospovidone at 2.0–4.0% w/w is therefore distributed extragranularly. Encapsulation is performed on a dosator or tamping-pin machine at 60,000–80,000 capsules/h; weight variation must meet USP <905> and Ph. Eur. 2.9.40. Dissolution is conducted in 0.1 N HCl at 37 °C and 50 rpm paddle with a release criterion of Q = 75% at 30 min as an internal specification. Terminal product forms are hard gelatin and HPMC capsules, with desiccants specified when equilibrium shell moisture exceeds 13.0% w/w at 25 °C/60% RH.
| Application scenario | Target zinc | TBZC input | TBZC fraction | Critical equipment parameter |
|---|---|---|---|---|
| Direct compression tablet | 25 mg | 42.2 mg | 8.4% w/w in 500 mg core | Main compression 12–18 kN |
| Hard gelatin capsule | 25 mg | 42.2 mg | 37.5% w/w in granulate | Roll compaction 5–12 kN/cm |
| Effervescent sachet | 50 mg | 84.4 mg | 1.69% w/w in 5.0 g fill | Disintegration < 5 min in 200 mL water |
| Parenteral solution | 10 mg/mL | 16.9 mg/mL | Not applicable | Final pH 4.5–6.0 |
| Pediatric dispersible sachet | 25 mg | 42.2 mg | 2.1% w/w in 2.0 g fill | Loss on drying < 2.0% w/w |
| Mucoadhesive lozenge | 10 mg | 16.9 mg | 0.94% w/w in 1.8 g lozenge | Melt granulation 80–90 °C |
Effervescent reconstitution of TBZC in 200 mL water at 15–25 °C is governed by the pH swing generated from citric acid and sodium bicarbonate; this is the critical process variable because TBZC remains largely undissolved above pH 5.5 and releases zinc ions only as the pH drops below approximately 4.5. The addition ratio is again derived from the 59.2% w/w zinc fraction: a 25 mg elemental zinc dose requires 42.2 mg TBZC, while 50 mg requires 84.4 mg. In a 5.0 g single-dose sachet, the TBZC loading is 0.84% w/w for 25 mg zinc and 1.69% w/w for 50 mg zinc; in a 3.2 g effervescent tablet, the loading is 1.32% w/w for 25 mg zinc. The granulation must be nonaqueous to prevent premature reaction; ethanol or isopropanol is used in high-shear granulation, followed by fluid-bed drying at inlet temperature 50–60 °C until loss on drying is below 0.8% w/w. The finalized granulate comprises sodium bicarbonate 45–55% w/w, citric acid anhydrous 25–35% w/w, sorbitol or mannitol 10–15% w/w, and PEG 6000 as a melt lubricant at 1.0–2.0% w/w. Effervescent tablets are compressed on a rotary press with chromium-plated tooling at 10–18 kN; sachets are filled on vertical form-fill-seal lines with a moisture barrier laminate. Compliance includes Ph. Eur. 2.9.1 disintegration in 200 mL water at 15–25 °C within 5 min, USP <711> dissolution in simulated gastric fluid, ICH Q3D, and 21 CFR 211.110 for blend uniformity. Terminal product forms are single-dose sachets and effervescent tablets, with desiccant closure systems required because moisture ingress above 1.5% w/w causes caking and carbon dioxide loss.
Parenteral zinc presentations derived from tetrabasic zinc chloride require an acidification step because the monohydrate is only sparingly water-soluble at neutral pH. The production sequence involves charging 16.9 mg TBZC per mL to Water for Injection for a 10 mg/mL elemental zinc target, adding concentrated hydrochloric acid slowly under nitrogen to reach a clear solution, then adjusting to pH 4.5–6.0 with sodium hydroxide. This acidification introduces chloride and sodium ions, which must be accounted for in the final label concentration and in compatibility with amino acid/dextrose admixtures. The solution is filtered through a 0.22 µm PVDF membrane, filled into Type I borosilicate glass vials or ampoules under nitrogen headspace, and autoclaved at 121 °C for 15 min. Terminal sterilization throughput is constrained by pH drift during autoclaving: if initial pH exceeds 5.8, post-sterilization zinc precipitation may occur as zinc hydroxide chloride species; if pH is below 4.0, container-closure leaching and pain on infusion increase. Compliance requires USP <1>, USP <71>, USP <85>, USP <788>, USP <790>, ICH Q3D parenteral elemental impurity assessment, and 21 CFR 210/211 aseptic-terminally sterilized processing. Published data for TBZC-derived parenteral zinc solutions under commercial registration are limited; any dossier must bridge to a recognized zinc chloride injection monograph or generate a full ICH-compliant development report. Terminal dosage forms are single-dose ampoules, vials, and pharmacy bulk packaging for parenteral nutrition admixtures, with a use limitation against direct subcutaneous or intramuscular injection without isotonicity and pH adjustment.
Dispersible pediatric zinc granules are manufactured by top-spray fluid-bed granulation with TBZC as the zinc source at low mass fractions to minimize metallic taste and gastric irritation. The addition ratio is fixed by the elemental zinc target per 5 mL reconstituted suspension: 25 mg zinc is derived from 42.2 mg TBZC; in a 2.0 g single-dose sachet this equals 2.1% w/w, while reduced mass 0.8–1.0 g sachets for infants contain 5.0–10.0% w/w TBZC. Hydroxypropyl cellulose or povidone K30 at 2.0–3.0% w/w is sprayed as an 8–12% aqueous solution; fluid-bed inlet temperature is 55–65 °C, product temperature 32–38 °C, atomizing pressure 1.0–1.8 bar, and final loss on drying below 2.0% w/w. After granulation, granules between 150 µm and 710 µm are filled into polyethylene-aluminium-polyester laminate sachets at not more than 25% RH. The granulate includes sucrose or maltodextrin, xanthan gum 0.5–1.5% w/w, and sodium benzoate 0.05–0.10% w/w. Reconstitution produces a suspension with pH 4.0–6.0 and apparent viscosity 80–150 mPa·s at 25 °C using a Brookfield RVT spindle at 63 rpm; this viscosity level prevents observable sedimentation of uncomplexed TBZC within 5 min. Compliance includes WHO pediatric dosage guidance, ICH Q3D, USP <701>, Ph. Eur. 2.9.1, and 21 CFR 211.110; release testing covers moisture, microbial enumeration, and zinc assay by complexometric titration or inductively coupled plasma optical emission spectrometry. Terminal product forms are single-dose dispersible granules, oral powder for constitution, and unit-dose suspension sachets.
In oral mucoadhesive lozenge matrices, tetrabasic zinc chloride functions as a slowly ionizing zinc source because its dissolution is accelerated by salivary buffers and organic acids. The addition ratio is determined by the astringency threshold rather than by compressibility: 10 mg elemental zinc requires 16.9 mg TBZC, which in a 1.8 g lozenge corresponds to 0.94% w/w; 25 mg zinc requires 42.2 mg TBZC, equivalent to 2.1% w/w in a 2.0 g lozenge. Loadings above 3.5% w/w produce gritty mouthfeel and a metallic astringency that cannot be fully masked by isomalt, sorbitol, or sodium cyclamate. The manufacturing route is melt granulation at 80–90 °C, followed by molding or low-force compression at 5–10 kN; TBZC remains chemically intact at these temperatures, and no aqueous granulation phase is used. Controlled release is achieved by incorporating hydroxypropyl methylcellulose K100M at 15–25% w/w or carbomer 934P at 5–10% w/w into a maltitol-sorbitol base, with dissolution tested in pH 6.8 phosphate buffer at 37 °C and 50 rpm paddle; the specification is Q = 75% at 30 min as a formulation-specific release limit. Erosion-controlled release approximates zero-order kinetics, but release rate is pH-dependent and published data for TBZC in this exact matrix are limited. Compliance is defined by 21 CFR 211, ICH Q3D, USP <711>, and Ph. Eur. 2.9.3 for dissolution. Terminal product forms are molded lozenges, compressed lozenge tablets, and sugar-free medicated confections; each primary package includes a desiccant when the lozenge base hygroscopicity exceeds 5.0% w/w at 40 °C/75% RH.
Competitive Tetrabasic Zinc Chloride (TBZC) 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!
Tetrabasic Zinc Chloride (TBZC) Pharma Grade API is the hydrated zinc chloride hydroxide described by the formula Zn5(OH)8Cl2·H2O, CAS 12167-79-2, with a molar mass of 535.88 g/mol. The theoretical zinc content is 61.0%, and a pharma-grade release specification normally spans 58.0–62.0% zinc on the dried basis. The material is a white to off-white, low-hygroscopicity powder intended for solid oral dosage forms and for acid-mediated conversion to injectable zinc chloride solutions.
The zinc concentration is the basis for dose conversion. Delivery of 25 mg elemental zinc requires 41.0 mg TBZC, corresponding to a mass conversion factor of 1.639 from elemental zinc to TBZC. This distinguishes TBZC from zinc sulfate heptahydrate and zinc gluconate, where the same elemental dose requires substantially greater excipient mass. The API is not a simple zinc chloride dihydrate and must not be treated as such in formula calculations or in acid-demand assessments.
Commercial pharma-grade designations are not harmonized across suppliers. The two most common trade forms are an unmilled powder with controlled top size and a jet-milled grade for low-dose direct blending. A supplier-specific grade code should be referenced in the regulatory file, but both forms are released against the same chemical identity, zinc content, and elemental impurity profile.
The release panel for a TBZC pharma-grade API is structured around three control objectives: confirmation of the zinc chloride hydroxide phase, control of toxic elements, and particle-size management for downstream unit operations. Where a pharmacopoeial monograph for TBZC is not adopted in the receiving market, zinc and chloride assay methods are validated under ICH Q2(R1); elemental impurities are aligned to ICH Q3D and tested using USP <232>/<233>. Loss on drying is measured by USP <731>, and particle size is measured by laser diffraction with sieving per USP <786>.
| Parameter | Acceptance criterion | Test method |
|---|---|---|
| Description | White to off-white powder | Visual against qualified reference |
| Zinc content | 58.0–62.0% Zn on dried basis | Complexometric titration with 0.1 M edetate disodium after acid dissolution |
| Chloride content | 12.0–14.0% | Argentometric titration after acid digestion |
| Loss on drying | ≤ 5.0% | USP <731> at 105 °C for 3 h |
| Particle size | D50 75–180 µm; jet-milled D90 ≤ 45 µm | Laser diffraction or sieving per USP <786> |
| Elemental impurities | Limits derived from ICH Q3D oral or parenteral daily exposure | USP <232>/<233> |
Because ICH Q3D sets permitted daily exposure rather than a fixed concentration in the API, the elemental impurity acceptance criterion must be calculated from the maximum intended daily dose of TBZC. A fixed limit stated without a dose basis is technically incomplete.
In a direct-compression platform running at 80,000–120,000 tablets/h on a rotary press, a formulation containing 41.0 mg TBZC per 500 mg tablet places the API at 8.2% w/w. At this level the powder flow is controlled mainly by the excipient system. Formulations at 25–35% w/w TBZC remain processable when the blend exhibits a Hausner ratio below 1.35. The unmilled material typically shows bulk density 0.45–0.65 g/cm³ and tapped density 0.60–0.85 g/cm³. Blending in a 100 L bin blender at 15 rpm for 20 min is common, but stratified sampling should confirm blend uniformity with RSD ≤ 5.0% for zinc before compression.
For granule manufacture, a wet granulation step using purified water or 2–4% w/w low-viscosity hydroxypropyl cellulose proceeds without phase changes because TBZC is practically insoluble in neutral water. The liquid addition should be kept below 18–22% w/w to avoid overwetting. Granule drying at inlet air 60–70 °C and product moisture ≤ 2.0% preserves subsequent tablet hardness. Acidic binders such as citric acid solution are not recommended in the same wet granulation because acid-mediated dissolution of TBZC releases zinc ions that can migrate during drying and cause surface enrichment or specking.
For capsule filling, the jet-milled grade with D90 ≤ 45 µm is preferred for low-dose zinc hard gelatin or HPMC capsules. The main process failure is not poor dissolution but segregation and stratification; therefore, the final blend should not be held beyond a validated hold time, frequently 4 h, without blending assurance data. Tablets formulated with TBZC generally disintegrate within 30 min in simulated gastric fluid pH 1.2 per USP <701>. Dissolution testing in pH 1.2 medium is more discriminating than pH 6.8 because the API dissolves by acid neutralization rather than by simple hydration. A discriminating oral solid test may use 900 mL of pH 1.2 hydrochloric acid at 75 rpm paddle speed with sampling at 15 min, 30 min, and 45 min.
For oral granules filled into stick packs, TBZC is dry-mixed with mannitol and low-substituted hydroxypropyl cellulose, then wet-massed with purified water. The granules are dried to moisture ≤ 2.0% and sieved through 0.8 mm mesh. The granule fraction below 150 µm should not exceed 20% w/w to prevent caking in the pack; the fraction above 1.0 mm should not exceed 5% w/w to maintain mouthfeel and reconstitution. Granulation reduces segregation that unmilled powder can exhibit in direct compression when the formulation contains wide differences in particle density.
Injectable manufacture converts TBZC to zinc chloride by reaction with hydrochloric acid. The stoichiometry is Zn5(OH)8Cl2·H2O + 8 HCl → 5 ZnCl2 + 9 H2O. Each gram of TBZC theoretically consumes 0.544 g of anhydrous HCl. In practice the dissolution vessel is charged with cold purified water, TBZC is dispersed with high-shear mixing at 1,500–2,500 rpm, and dilute hydrochloric acid is metered slowly to maintain pH 2.0–3.0. The vessel is blanketed with filtered air if carbon dioxide ingress reduces acid efficiency.
The resulting solution is filtered through 0.22 µm polyvinylidene fluoride or polyethersulfone membranes before steam sterilization at 121 °C for 15 min. pH is checked per USP <791>; values above 5.5 during neutralization or buffer addition generate zinc hydroxide floc that can clog the sterile filter. Phosphate buffers are incompatible because zinc phosphate precipitates even at pH 3.0; sodium chloride is used for tonicity adjustment. The final solution is assayed for zinc content by complexometric titration and must meet 95.0–105.0% of the labeled zinc chloride content. The injectable route requires a high degree of clarity; particle counts should be monitored after terminal sterilization because post-sterilization precipitation is a recognized failure mode in zinc-containing parenterals formulated above pH 4.0.
Comparability among zinc sources is based on elemental zinc content, dissolution dependence, and reaction with common excipients. The table below compares TBZC with zinc sulfate heptahydrate, zinc oxide, and zinc gluconate. The same elemental dose cannot be assumed bioequivalent without dissolution testing and, where required, in vivo data.
| Property | TBZC | Zinc sulfate heptahydrate | Zinc oxide | Zinc gluconate |
|---|---|---|---|---|
| Theoretical zinc content | 61.0% | 22.7% | 80.3% | 14.3% |
| Solubility in neutral water | Practically insoluble | Freely soluble | Practically insoluble | Soluble |
| Dissolution dependence | Acid-mediated | pH-independent | Acid-mediated | pH-independent |
| Hygroscopicity | Low | High | Low | Moderate |
| Mass for 25 mg elemental zinc | 41.0 mg | 110.1 mg | 31.2 mg | 174.3 mg |
| Solution pH behavior | Basic, acid-consuming | Acidic | Basic | Neutral to weakly acidic |
TBZC has a lower hygroscopicity than zinc sulfate heptahydrate, which reduces agglomeration during humid processing, but it is not free-flowing under all conditions. The basic salt character means that acidic vehicles or acidulants must be evaluated for acid demand. In an effervescent or acidic drink powder, TBZC consumes acid and can slow disintegration or raise final pH if the acidulant is not compensated. Avoid combination with amine-based additives in aqueous granulation because zinc can form zinc-amine complexes that alter dissolution and may produce colored species. Direct blending with hygroscopic acidic salts such as ascorbic acid is not recommended unless a protective excipient layer is used.
For shipments crossing tropical maritime routes, TBZC pharma grade is packed in double low-density polyethylene liners inside a sealed HDPE drum with desiccant. The storage boundary is 15–25 °C and relative humidity below 60%; excursions above 75% RH for more than 24 h may cause surface caking, although the hydrate does not deliquesce. Containers should be opened in a 21 ± 2 °C warehouse and resealed under nitrogen if the remaining quantity is to be held beyond 30 days. Stability studies under ICH Q1A conditions of 25 °C/60% RH and 40 °C/75% RH typically monitor zinc assay, chloride content, and loss on drying; published data for this specific TBZC configuration is limited, so supplier stability data should be reviewed against the contract acceptance criteria.
TBZC should not be stored near volatile acids, strong alkalis, or ammonia. Chloride exchange in acidic vapor and formation of zinc-ammine surface species can alter the powder surface and reduce acid dissolution rate. These limitations are material-level incompatibilities and should be captured in the supplier quality agreement rather than inferred from finished-product performance.
The API is manufactured under ICH Q7 conditions; batch records should include identity, assay, elemental impurities, loss on drying, and particle-size release data. Because ICH Q3D sets permitted daily exposure rather than concentration, the elemental impurity limit is converted to an API acceptance criterion using the maximum intended daily dose of TBZC. For a maximum daily TBZC dose of 82 mg delivering 50 mg elemental zinc, a parenteral lead PDE of 5 µg/day yields an API lead limit of 61 µg/g if no other lead source is present. This calculation must be repeated for the registered formulation and route of administration.
The control of the zinc chloride hydroxide phase is supported by X-ray powder diffraction using Cu Kα radiation. Acceptance is made against a qualified reference diffractogram rather than d-spacing alone. Residual solvents are controlled per USP <467>; TBZC produced from aqueous reaction routes typically reports below 0.1% total residual solvents, but process-specific data remain the release basis. Cleaning validation for multipurpose equipment uses rinse conductivity and zinc recovery by atomic absorption or inductively coupled plasma; the acceptance criterion is typically not more than 10 ppm zinc in the final rinse. The absence of animal-origin starting materials supports a BSE/TSE statement, but each site must confirm the raw-material supply chain for the specific product code.
