| HS Code | 839895 |
| Product Name | Griseofulvina Tablets Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable |
| Inn | Griseofulvin |
| Synonyms | Griseofulvin, Grisactin, Fulvicin, Grifulvin V, Gris-PEG, Griseofulvina |
| Cas Registry Number | 126-07-8 |
| Molecular Formula | C17H17ClO6 |
| Molecular Weight | 352.77 g/mol |
| Chemical Name | (2S,5'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H,4'H-spiro[1-benzofuran-2,1'-cyclohex[2]ene]-3,4'-dione |
| Appearance | White to off-white crystalline powder |
| Odor | Odorless or practically odorless |
| Melting Point | 218-224 °C |
| Solubility | Practically insoluble in water; soluble in dimethyl sulfoxide, dimethylformamide, chloroform, acetone, methanol, ethanol |
| Assay Purity | 98.0% to 102.0% (on dried basis) |
| Pharmacopoeia Grade | Pharma Grade / API Grade |
| Pharmacopoeia Compliance | USP, EP, BP, JP |
| Loss On Drying | ≤ 0.5% |
| Residue On Ignition | ≤ 0.2% |
| Heavy Metals | ≤ 20 ppm |
| Storage Conditions | Store in a cool, dry place, protected from light, in tightly closed containers |
| Shelf Life | 2-5 years if stored properly |
| Packaging | 25 kg fiber drums with double polyethylene bags, or as per customer requirement |
| Dosage Forms | Tablet, Capsule, Granule, Injection |
| Route Of Administration | Oral, Injectable |
| Therapeutic Category | Antifungal antibiotic |
| Mechanism Of Action | Inhibits fungal cell mitosis by interfering with microtubule function and binding to tubulin |
| Pharmacokinetics | Absorption from gastrointestinal tract is variable; half-life approximately 9-24 hours; metabolized in liver; excreted in urine and feces |
| Hs Code | 29419000 |
| Manufacturer | Various GMP-certified manufacturers |
| Country Of Origin | China, India, European Union |
| Regulatory Status | API for pharmaceutical manufacturing; subject to local regulations |
As an accredited Griseofulvina Tablets 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.
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On rotary tablet press lines handling ultramicronized griseofulvin, the first processing constraint is not API chemical instability but the micromeritic profile of the incoming powder: bulk density in the range 0.25–0.38 g/mL, angle of repose frequently above 45° without glidant aid, and electrostatic adhesion to stainless steel contact surfaces when ambient relative humidity falls below 30% RH. The incoming particle-size distribution is therefore monitored at receiving by laser diffraction per ISO 13320, with D90 ≤ 5 µm and D50 ≤ 3 µm acting as internal pass criteria; a shift to D90 > 10 µm correlates with slower dissolution and batch rejection in USP <711> testing. A wet-granulation architecture is used for 125 mg, 250 mg, and 500 mg film-coated immediate-release tablets. The formulation addition ratio for ultramicronized API is maintained at 35–48% w/w, with lactose monohydrate and microcrystalline cellulose as the main diluents, croscarmellose sodium at 2–4% w/w, povidone as binder at 1–3% w/w, and magnesium stearate at 0.5–1.0% w/w. In a 300 L high-shear mixer, the API is pre-blended with lactose and microcrystalline cellulose for 5–8 min at impeller tip speed 5–7 m/s; purified water is metered at 0.8–1.2 kg/min until granule moisture reaches 1.5–2.5% w/w. Exceeding 2.5% w/w moisture produces adhesive granules that collect on the mixer lid and cone-mill surfaces; below 1.5% w/w, the granulation is brittle and generates excessive fines after dry milling. Wet mass is passed through a cone mill with a 1.0 mm grater screen, dried in a fluid-bed dryer with inlet air at 55–65°C to a final loss-on-drying of 0.8–1.2% w/w, and dry-milled through a 0.8 mm screen. Lubrication with magnesium stearate is limited to 3–5 min because extended lubrication beyond 5 min has shown a measurable dissolution slowdown in USP <711> apparatus II at 75 rpm in 0.54% w/v sodium lauryl sulfate. The lubricated blend is compressed on a 45-station rotary press with precompression 5–8 kN and main compression 12–25 kN, targeting hardness 80–150 N and friability ≤0.8% w/w. The core is film-coated in a side-vented pan at exhaust air temperature 55–65°C, with pan speed 2–6 rpm, to a weight gain of 2–4% w/w. Compendial boundaries include the USP Griseofulvin Ultramicrosize Tablets monograph, USP <905> uniformity of dosage units, USP <921> water determination, ICH Q3D elemental impurities, and 21 CFR Part 211. Ultramicronized and microsize grades are not dose-equivalent; the ultramicronized form is generally administered at approximately 66–75% of the microsize oral dose, so tablet strengths must be declared with the particle-size grade on the label.
Micronized griseofulvin capsules are run on dosator-type encapsulators at 40,000–75,000 capsules/h, but the low bulk density of the API—commonly 0.30–0.45 g/mL after milling to D90 5–10 µm measured by laser diffraction per ISO 13320—creates a specific failure mode: high tamping pin speed generates plug density gradients, with the bottom plug segment denser than the top segment, causing content uniformity deviations and delayed capsule shell disintegration. The capsule blend is therefore formulated with 30–45% w/w micronized API, 35–55% w/w mannitol or lactose monohydrate, 5–15% w/w microcrystalline cellulose, 2–4% w/w croscarmellose sodium, 0.5–1.0% w/w colloidal silicon dioxide, and 0.25–1.0% w/w sodium stearyl fumarate. The API is first passed through a 30-mesh stainless steel screen and then blended in a 1,000 L bin blender at 8–12 rpm for 25–40 min; blending times above 50 min can segregate the low-density micronized material toward the top of the bin, producing tail-end weight variability. Tamping pin compression force is maintained between 40–100 N, and plug height is adjusted by pin depth rather than increasing speed. Filled capsules pass through automated weight sorters and metal detectors; compendial controls include USP <905> weight variation, Ph.Eur. 2.9.40 uniformity of dosage units, USP <467> residual solvents, and ICH Q3D elemental impurities. Terminal products are 125 mg and 250 mg hard gelatin and HPMC capsule strengths for oral administration. Where capsule shells are of HPMC rather than gelatin, dissolution testing should account for the slightly longer shell rupture time at 37±0.5°C in 0.1 N hydrochloric acid, because HPMC shells may retain the griseofulvin plug for 2–5 min longer than gelatin.
Pediatric oral granules are manufactured as dry-bottle fill blends that are reconstituted to 125 mg/5 mL griseofulvin oral suspension. Because the suspending vehicle is absent at the blending stage, the API must be distributed in a sucrose-based carrier at 2–8% w/w to prevent high-dose dry pockets that would not redisperse uniformly. The granule component is prepared by initially triturating micronized griseofulvin with a wetting agent such as polysorbate 80 at 0.1–0.3% w/w of the dry blend, then adding that concentrate to sucrose in a ribbon blender at 25–50 rpm for 15–30 min. Xanthan gum or sodium carboxymethylcellulose is included at 0.5–2.0% w/w to control sedimentation volume after reconstitution; sodium benzoate at 0.1–0.2% w/w is used as preservative, with preservative efficacy verified according to USP <51>. The reconstituted suspension pH is controlled between 5.0 and 7.0; alkaline conditions above 7.0 accelerate hydrolysis of the lactone ring. The dry powder is filled into 100 mL or 120 mL HDPE bottles under ≤30% RH ambient humidity, with headspace desiccant where the closure configuration permits. Reconstitution is performed with purified water to a volumetric mark; the final suspension is tested against sedimentation volume ≥0.9 at 24 h and redispersibility within 15 s of shaking. Terminal product types are 125 mg/5 mL oral suspension bottles and unit-dose sachet granules intended for reconstitution by the caregiver. Regulatory references include the USP Griseofulvin Oral Suspension monograph, Ph.Eur. 2.9.40 uniformity of dosage units, USP <921> water determination, and ICH Q3B degradation products. A production-scale failure mode occurs when the API is added directly to the sucrose bed without the wetting-agent premix: electrostatic clumping produces visible yellow aggregates that remain on the bottle wall after shaking.
Parenteral use of griseofulvin has no compendial monograph in USP or Ph.Eur., and no commercial injectable product is listed in the FDA Orange Book or EMA registers. Injectable-grade API offered for development therefore enters preformulation rather than established production. The limiting technical parameter is aqueous solubility, reported as approximately 8.6 mg/L at 25°C; intravenous or intramuscular delivery requires nanonized suspension, cyclodextrin complexation, or co-solvent solubilization. In feasibility batches using hydroxypropyl-β-cyclodextrin or sulfobutyl ether β-cyclodextrin, the API-to-carrier molar ratio is screened between 1:2 and 1:4, with total solids before lyophilization kept at 5–15% w/v to avoid precipitation during sterile filtration. Aseptic processing consists of dissolving the complex in water for injection, filtering through a 0.22 µm PVDF or PES membrane, filling into Type I glass vials, and lyophilizing; primary drying is controlled between −25°C and −20°C, followed by secondary drying at 20–25°C. Terminal product types are lyophilized powder for solution/injection and sterile nanonized suspension for investigational administration; published data for this specific configuration is limited. Compliance for any investigational batch must follow 21 CFR Part 210/211, USP <1> injections, USP <71> sterility, USP <85> bacterial endotoxins, USP <788> particulate matter, ICH Q3D elemental impurities, and ICH M7 where mutagenic impurities are assessed. Because no commercial injection monograph exists, formulation addition ratios must be justified by phase-solubility, filter-compatibility, and stability data rather than compendial precedent.
Veterinary oral use of griseofulvin in equine and companion-animal dermatophytosis is established in several jurisdictions, but the terminal product is not a human oral solid dose. The manufacturing route is a feed premix or oral granule intended for mixing with feed at point of administration. A typical premix contains 1–10% w/w griseofulvin on a lactose monohydrate or ground corn cob carrier; a light coating of vegetable oil or starch at 0.5–1.5% w/w is applied after blending to reduce electrostatic segregation and dust formation. Blend uniformity is achieved in a ribbon mixer at 25–50 rpm for 15–30 min, with moisture controlled to ≤10% w/w and particle size distribution checked to avoid settle-out during transport. Terminal types include 1% w/w and 5% w/w oral granules for equine administration, and lower-strength premixes used by compounding pharmacies to fill veterinary capsules. Regulatory compliance is jurisdiction-dependent; applicable frameworks include VICH GL18, EU Regulation 2019/6 for veterinary medicinal products, and FDA 21 CFR Part 225 for medicated feed manufacturers where the drug is approved for that use. Griseofulvin is not approved for food-producing animals in several regions, so withdrawal periods and in-feed approvals require species-specific verification before commercial distribution.
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Griseofulvina Tablets Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is a fermentation-derived antifungal active pharmaceutical ingredient supplied as a white to pale yellow crystalline powder. The trade name designates a multi-dosage-form grade; it is not a finished tablet or sterile injectable solution. The API is produced from Penicillium griseofulvum fermentation and purified to pharmacopoeial monograph standards. Its molecular formula is C17H17ClO6, with a relative molecular mass of 352.77 and CAS registry 126-07-8. The compound is practically insoluble in water, soluble in dimethylformamide and dichloromethane, and classified as a low-solubility, high-permeability BCS Class II drug substance. Oral solid dose processing requires particle size reduction, while injectable use adds sterility and depyrogenation controls. The product differs from unmicronized, technical, or veterinary grades by controlled particle size distribution, compendial impurity limits, residual solvent profile, elemental impurity data, and microbiological release.
Release documentation for a non-sterile oral grade includes infrared absorption spectrophotometry, a melting range of 218 °C to 224 °C, an HPLC assay of 97.0% to 102.0% on the dried basis, and specific rotation in dimethylformamide between +354° and +364° when tested per USP <781>. Water content by Karl Fischer titration is routinely controlled at ≤0.5%, loss on drying at ≤0.5%, and residue on ignition at ≤0.1%. Residual solvents are determined by headspace gas chromatography under USP <467> and ICH Q3C; elemental impurities are managed by ICH Q3D and measured by ICP-MS under USP <232>/<233>. Related substances resolved by reversed-phase HPLC include dechlorogriseofulvin and dehydrogriseofulvin; total and individual impurity limits follow the current USP, Ph. Eur., and BP monographs. Microbiological examination for oral-grade material is performed by USP <61> and <62>. Powder X-ray diffraction is used to confirm the crystalline polymorph because amorphous or solvated forms can alter dissolution and processing behavior.
Polymorph control is monitored by X-ray powder diffraction and differential scanning calorimetry; griseofulvin exhibits a characteristic endotherm near 218–222 °C. Seed crystals and controlled cooling during recrystallization determine crystal habit and aspect ratio. High aspect ratio needles are more cohesive and less free-flowing than equant crystals. Batch-to-batch variation in particle morphology is a known processing bottleneck; a jet mill with controlled classifier speed and injector gas pressure can normalize particle size but not always particle shape. Incoming material should therefore be evaluated by scanning electron microscopy or dynamic image analysis when flow is critical. Because griseofulvin is produced by fermentation, downstream purification must remove biomass-derived pigments and related fungal metabolites. Recrystallization from solvent systems is used, with solvent classes controlled under ICH Q3C. Process-validation batches should demonstrate solvent clearance below thresholds and absence of mutagenic impurities identified in the ICH M7 risk assessment. The API is light-sensitive and should be packaged in opaque HDPE bags within sealed aluminium laminates.
| Attribute | Oral-grade release criterion | Injectable-grade additional criterion | Test method |
|---|---|---|---|
| Identification | Infrared absorption; melting range 218–224 °C | Same | USP <197>, USP <741> |
| Assay | 97.0–102.0% on dried basis | Same | HPLC per USP <621> |
| Particle size | D90 ≤10 µm; D50 2–5 µm | Suspension-specific; narrower PSD; terminal sterilization impact assessed | Laser diffraction per USP <429> / ISO 13320 |
| Bacterial endotoxins | Not required | Supports final product limit under USP <85> | LAL kinetic chromogenic |
| Sterility | Not required | Final product complies USP <71> | Membrane filtration |
| Elemental impurities | ICH Q3D oral PDE | ICH Q3D parenteral PDE | USP <232>/<233> |
| Residual solvents | USP <467>, ICH Q3C | Same | Headspace GC |
Production-scale experience with jet-milled griseofulvin indicates that triboelectric charging becomes process-limiting when relative humidity exceeds 55–60%; the API should be discharged from the mill and blended in a humidity-controlled room. On rotary tablet presses using 10 mm round tooling at speeds between 40,000 and 80,000 tablets/h, segregation of the micronized API from coarse fillers can produce content uniformity drift if blend hold times exceed 20–30 min or if the blender discharge step induces fines migration. These failure modes are managed with low-shear tumble blending, 0.5% colloidal silicon dioxide, and periodic sampling under USP <905>. A higher surface area is not universally beneficial: highly micronized powder can exhibit lower bulk density, greater electrostatic charge, and re-agglomeration during storage at elevated humidity. Stability studies should monitor particle size, water content, and dissolution after storage at 25 °C/60% RH and 40 °C/75% RH per ICH Q1A. Milling-induced amorphization on particle surfaces can create local disorder that accelerates water uptake; if the X-ray diffractogram remains crystalline, the bulk dissolution advantage is retained.
Griseofulvin has reported aqueous solubility near 8.6 mg/L at 25 °C, so dissolution rather than membrane permeability controls absorption. Micronization increases the specific surface area and decreases the diffusion boundary layer thickness in the Noyes-Whitney model. Jet milling to a volume median diameter of 2–5 µm and a D90 ≤10 µm substantially raises the fraction dissolved in compendial dissolution tests; exact values vary with surfactant type, medium pH, and apparatus. Unmicronized API with D90 >50 µm is unsuitable for direct compression or direct capsule filling because batch-to-batch dissolution variance and content uniformity fluctuations exceed pharmacopoeial acceptance limits. Low-dose tablet and capsule formulations require ordered mixing: the micronized fines adhere to coarser carrier particles, and a narrow span below 2.0 reduces segregation in the tablet press feed frame. Dissolution screening is commonly performed in USP apparatus 2 at 100 rpm with 0.54% sodium lauryl sulfate medium, but the choice of medium must be justified because the API’s wetting is surfactant-dependent.
Ultramicronized griseofulvin is a separate product category with a larger specific surface area and a smaller median particle size than microsize material. The surface area measured by BET nitrogen adsorption is typically reported in the certificate of analysis; values for micronized material differ by milling equipment, feed rate, and classifier setting. On a production-scale spiral jet mill, the final particle size is controlled by nozzle pressure, feed rate, and classifier speed. If mill pressure is too high, surface amorphization and static charging increase; if too low, the D90 ≤10 µm release criterion may not be met. Dry powder blending at high shear may raise product temperature and cause particle aggregation; low-shear blending or inclusion of fumed silica is preferred. These controls are common to poorly soluble micronized APIs and are not unique to griseofulvin. The assay by HPLC typically uses a 250 mm × 4.6 mm octadecylsilane column with UV detection near 291 nm; system suitability requires resolution between griseofulvin and its related substances. API for capsule and tablet manufacture is commonly specified with a bulk density of 0.25–0.45 g/mL after micronization and tapped density consistent with a Hausner ratio below 1.35. These limits are not monograph requirements but are set in quality agreements because flow affects high-speed capsule filling.
When the API is ordered for injectable suspension, the micronization protocol alone is insufficient. Sterility assurance must start at the API or be achieved by terminal sterilization of the formulated suspension; bacterial endotoxin and particulate matter must comply with USP <85> and USP <788> in the final dosage form. Because griseofulvin is practically insoluble and cannot be sterile-filtered as a solution, an injectable route requires either aseptic crystallization to a controlled particle size, sterilization of the dry micronized powder by gamma irradiation or ethylene oxide, or terminal autoclaving of an aqueous suspension after formulation. Published data for production-scale sterile griseofulvin suspensions is limited; each supplier’s injectable grade should be qualified for autoclave cycle stability, container-closure compatibility, particle growth during storage, and endotoxin recovery before process validation.
Griseofulvin acts by binding fungal tubulin and disrupting mitotic spindle formation. Azole antifungals such as fluconazole and itraconazole inhibit lanosterol 14α-demethylase, and the allylamine terbinafine inhibits squalene epoxidase. This mechanistic difference restricts griseofulvin’s spectrum to dermatophyte infections caused by Trichophyton, Microsporum, and Epidermophyton; it is not indicated for Candida albicans or Aspergillus fumigatus. Processing differences are equally sharp: fluconazole is sufficiently water-soluble for intravenous solution preparation, while griseofulvin requires micronization for oral absorption and a suspension or solid-in-oil carrier for parenteral study. Terbinafine hydrochloride has different tablet excipient interactions and is used at lower unit doses. Griseofulvin’s melting range of 218–224 °C provides thermal stability during wet granulation, drying, and film coating, but its particle-size sensitivity is more severe than that of soluble azoles. The narrow-spectrum profile affects formulation strategy: griseofulvin is not suitable for broad fungal coverage in a topical or intravenous product, whereas azoles may be used across Candida and Aspergillus. In contrast to terbinafine, griseofulvin has an established fermentation-derived impurity profile; terbinafine is synthetic.
For granule and tablet intermediate production, wet granulation is used with aqueous or hydroalcoholic binders; because the API is hydrophobic, sodium lauryl sulfate is added at 0.5–1.0% by weight to improve wetting and reduce drug-rich granule formation. Dry granulation by roller compaction is used for water-sensitive formulations; ribbon density is typically controlled between 0.80 and 1.10 g/cm³ to balance tablet hardness and disintegration. Fluid-bed granulation produces granules with lower bulk density and faster disintegration than high-shear granulation, but the fines content can shift particle size distribution. Encapsulation on high-speed dosator machines requires fill weight RSD below 2.0%; preblending with 0.2–0.5% magnesium stearate and 0.5% colloidal silicon dioxide reduces static charge and improves flow. Tablets compressed to hardness 50–80 N and friability below 1.0% under USP <1216> are typical, though final parameters must be set by the formulation.
Compared with veterinary or technical grades, the pharma-grade material is distinguished by a documented ICH M7 mutagenic impurity assessment, ICH Q3D elemental impurity risk summary, residual solvent testing under ICH Q3C, and absence of uncharacterized fermentation co-metabolites above monograph thresholds. It is not interchangeable with unmicronized griseofulvin, because particle size distribution directly affects dissolution, content uniformity, and in vivo bioequivalence. It is also not interchangeable with research-grade griseofulvin, which may not carry a full drug master file or GMP release. For tablet, capsule, granule, and injectable development, the appropriate grade is selected on the basis of particle size target, sterility claim, endotoxin budget, and process-validation support.
