| HS Code | 491921 |
| Product | Idarubicin Pharma Grade API |
| Chemical Class | Anthracycline antibiotic |
| Molecular Formula | C26H28ClNO9 (hydrochloride salt) |
| Molecular Weight | 533.96 g/mol |
| Cas Number | 57823-29-1 (hydrochloride); 58957-92-9 (base) |
| Description | Orange-red to red crystalline powder |
| Solubility | Soluble in water; sparingly soluble in methanol; practically insoluble in acetone |
| Purity | 98.0% to 102.0% by HPLC on an anhydrous basis |
| Storage | Store at 2-8°C in a tightly closed container, protected from light and moisture |
| Shelf Life | Typically 24 months from date of manufacture |
| Indication | Used as an antineoplastic agent for the treatment of acute myeloid leukemia and other cancers |
| Mechanism | DNA intercalation and topoisomerase II inhibition, thereby blocking DNA replication |
| Dosage Forms | Suitable for tablet, capsule, granule, oral and injectable dosage forms |
| Routes Of Administration | Oral and intravenous (injection) |
As an accredited Idarubicin 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 | Packaged in sealed, light-protective containers, Idarubicin Pharma Grade API available in 100 mg quantity for oral and injectable dosage forms. |
| Container Loading (20′ FCL) | 20′ FCL loaded with palletized, temperature-controlled drums of Idarubicin Pharma Grade API for oral and injectable dosage forms. |
| Shipping | Idarubicin Pharma Grade API ships in temperature-controlled, tamper-evident, hazardous-material-compliant packaging. As a cytotoxic compound, it requires sealed containment, absorbent cushioning, and clear warning labels. Shipments include chain-of-custody documentation and are delivered only to licensed, authorized pharmaceutical recipients under strict regulatory handling protocols. |
| Storage | Store Idarubicin Pharma Grade API tightly closed in its original container, protected from light and moisture. Store in a secure, well-ventilated area at controlled room temperature between 20–25°C, with excursions permitted to 15–30°C. Handle only under containment with appropriate cytotoxic drug precautions to prevent contamination and exposure. |
| Shelf Life | Idarubicin API shelf life is 24 months from manufacture when stored under controlled conditions, protected from light and moisture. |
For sterile injectable presentations, idarubicin hydrochloride monohydrate is dissolved in Water for Injection at 2–8 °C under a nitrogen overlay because the glycosidic bond between the tetracyclic chromophore and the daunosamine sugar is susceptible to hydrolytic cleavage in neutral and alkaline media. A bulk solution containing idarubicin HCl equivalent to 1 mg/mL idarubicin base and lactose monohydrate 50 mg/mL as a bulking agent is adjusted with 0.1 M hydrochloric acid or sodium hydroxide to pH 3.0–4.5; the acidic range preserves the anthraquinone moiety and reduces aglycone formation. The compounded solution is sterile-filtered through a 0.22 μm PVDF or PES membrane and filled into Type I borosilicate glass vials under ISO Class 5 conditions in accordance with ISO 14644-1:2015. For lyophilized presentations, the filled vials are subjected to a product-specific freeze-drying cycle: freezing to −40 °C, primary drying at shelf temperatures between −10 °C and 0 °C and chamber pressure of 80–150 mTorr, followed by secondary drying at 20–25 °C. Published freeze-drying cycle data specific to idarubicin hydrochloride is limited; therefore thermal characterization by differential scanning calorimetry and freeze-drying microscopy is required to define the design space under ICH Q8(R2). The finished injectable is tested for pH by USP <791>, particulate matter by USP <788>, bacterial endotoxins by USP <85>, sterility by USP <71>, and assay/related substances by a stability-indicating HPLC method validated under ICH Q2(R1). Admixture incompatibility with heparin sodium and fluorouracil has been reported for anthracycline infusions; no additional drug should be introduced into the infusion container unless visual and subvisible particle data per USP <788> demonstrate compatibility. The terminal sterile drug product is protected from light and stored at 2–8 °C; photodegradation of the anthracycline chromophore can generate inactive aglycone impurities that alter both safety and potency.
| Quality Attribute | Test Method / Standard | Typical Release Boundary |
|---|---|---|
| Solution pH | USP <791> | 3.0–4.5 |
| Particulate matter ≥10 μm and ≥25 μm | USP <788> | Small-volume injection limits: ≤6000 and ≤600 per container, respectively |
| Bacterial endotoxins | USP <85> | Calculated from maximum adult dose and K/M threshold |
| Assay of idarubicin HCl | HPLC / USP <621> | 95.0–105.0% label claim |
| Degradation products | ICH Q3B | Reporting 0.1%; identification/qualification per maximum daily dose thresholds |
| Sterility | USP <71> | No growth in 14-day direct inoculation |
The practical objection to aqueous wet granulation for idarubicin HCl is the combination of moisture, localized heat, and shear that promotes hydrolytic removal of the amino sugar. In a high-shear granulator, water addition produces a granule bed with transient moisture content of 8–12% w/w and a temperature rise above 40 °C due to impeller friction; under these conditions the anthracycline glycosidic bond can undergo first-order hydrolytic degradation, producing the non-glycosidic aglycone. If a wet granulation route is nonetheless required for particle size growth, the process should be converted to non-aqueous granulation with absolute ethanol or isopropanol in a 10–25 L high-shear granulator. Povidone K30 dissolved at 5–10% w/v in the selected solvent is applied as a binder at 2–4% w/w dry polymer; granulation is conducted at impeller speed 200–400 rpm, chopper speed 1000–1500 rpm, and wet massing time 60–180 seconds. The wet granules are dried in a fluid-bed dryer at inlet air temperature 35–45 °C until loss on drying is ≤ 2.0% w/w by USP <731>. Residual solvent is controlled under USP <467> Option 1 for Class 3 solvents. The dried granules are milled through a 0.8 mm conical sieve and either filled into capsules or compressed into tablets; the terminal dosage form carries the full degradation-product burden of ICH Q3B, with any unspecified impurity above 0.2% requiring toxicological qualification unless it is a known inactive metabolite. Published data for idarubicin-specific granulation kinetics remains limited; forced degradation studies under ICH Q1A conditions are required to set a safe drying endpoint.
Directly after dry blending, a low-dose idarubicin core may be compressed on a rotary tablet press equipped with an external lubrication system to reduce the risk of punch filming and segregation. A feasibility core targeting 5 mg idarubicin base per 120 mg core gives 4.2 wt% active loading; the filler system comprises spray-dried lactose monohydrate or microcrystalline cellulose PH102 at 70–85 wt%, crospovidone at 2–4 wt%, colloidal silicon dioxide at 0.25–0.5 wt%, and magnesium stearate at 0.5–1.0 wt%. The active is pre-blended with a 1:5 portion of filler and screened through a 600 μm sieve before introduction into a V-blender or bin blender. Blend uniformity is evaluated at 10 sampling positions with a validated HPLC method per ICH Q2(R1); the acceptance value under USP <905> must not exceed 15 at first stage. Tablet cores are made on a 10–20 station rotary press at 20–40 rpm turret speed, with hardness 4–7 kp per USP <1217> and friability ≤ 1.0% per USP <1216>. If immediate release is not acceptable because of gastric degradation, the core is film-coated with an enteric methacrylic acid copolymer; the final coated tablet is tested by two-stage dissolution in 0.1 M hydrochloric acid followed by pH 6.8 phosphate buffer under USP <711>. The direct compression route limits hydrolytic degradation but produces a terminal tablet that is highly sensitive to blend segregation because the active particle size may differ from the filler; this is the controlling limit for scale-up and requires periodic stratified sampling from the compression hopper.
| Oral Solid Attribute | Standard | Development Release Target |
|---|---|---|
| Content uniformity | USP <905> | Acceptance value ≤ 15 |
| Tablet friability | USP <1216> | ≤ 1.0% |
| Dissolution | USP <711> | Q ≥ 75% at 45 min in specified media |
| Residual solvents | USP <467> | Class 3 solvent limits; no Class 1 |
| Moisture / loss on drying | USP <731> | ≤ 2.0% w/w |
| Elemental impurities | ICH Q3D | Permitted daily exposure by route |
When roller compaction is selected for a moisture-sensitive anthracycline, the dry granulation step must be designed to produce granules with a solid fraction between 0.55 and 0.75 because overcompaction reduces tabletability and undercompaction produces fines that segregate. A starting blend for idarubicin HCl granules may contain active equivalent to 5 mg per unit, microcrystalline cellulose PH102 at 60–75 wt%, lactose monohydrate at 15–25 wt%, crospovidone at 3–5 wt%, and magnesium stearate at 0.5 wt%; the mixture is pre-lubricated before compaction to prevent sticking to the rolls. Roller compaction is performed on an instrumented roller compactor with roll pressure 4–8 kN/cm, roll speed 2–6 rpm, and screen size 1.0 mm for granule milling; the compacted ribbons are assessed for solid fraction by volume displacement and bulk density per USP <616>. Granules are then filled into hard gelatin capsules on a dosing disk or tamping pin machine at a fill weight of 120–150 mg. The terminal product is an oral granule or capsule that must meet USP <905> uniformity and USP <711> dissolution. The key thermal limitation is that the compaction zone temperature should remain below 35 °C to limit degradation; ribbon surface temperature should be monitored with an infrared sensor and recorded in the development report under ICH Q8(R2). Published data for idarubicin-specific roller compaction parameters is limited; the stated ranges are starting points requiring design-of-experiment confirmation.
During automatic capsule filling, low-dose cytotoxic blends require repeated measurement of net fill weight variability because the active content per capsule is a function of both blend potency and fill mass. A two-stage filling process on a dosator-type capsule machine may be used for idarubicin granules; dosator chamber length is set to achieve a tapped density target of 0.65–0.80 g/mL, and the powder bed height is maintained within ±5 mm to control fill weight. For idarubicin HCl granules, the target fill weight has a tolerance of ±3% around the set point; weight sorting on an automatic capsule checkweigher rejects units outside ±5% before metal detection. The finished capsules are tested according to USP <905>; if the active represents less than 50% of the fill weight, weight variation may be used instead of content uniformity only when blend potency is demonstrated to be uniform, but individual capsule HPLC assay is the more conservative approach for a cytotoxic anthracycline. The container closure system must protect the capsules from light and moisture; HDPE bottles with desiccant canisters or cold-form aluminum blisters are used. A desiccant silica gel quantity of 1–2 g per 60 mL bottle may be adjusted based on moisture uptake studies under ICH Q1A accelerated conditions at 40 °C/75% RH for 6 months. The terminal product is a hard gelatin or hypromellose capsule with enteric coating if gastric degradation of idarubicin is confirmed. Environmental controls during capsule filling follow USP <800> and NIOSH hazardous drug handling guidance; any breach of containment requires batch assessment under ICH Q9.
Because idarubicin is a substrate of P-glycoprotein and undergoes significant first-pass metabolism, oral absorption of the free base and hydrochloride salt is constrained by intestinal efflux and not solely by aqueous solubility. Oral pharmacokinetic development of idarubicin has been limited by variable systemic exposure; published data for idarubicin oral capsules remains sparse relative to the injectable route, so formulation work must include dissolution in biorelevant media and permeability screening. The BCS classification of idarubicin is not definitively assigned in the ICH M9 framework; however, its reported low oral bioavailability and P-gp substrate profile place it in the high-extraction, efflux-limited category. In vitro dissolution testing under USP <711> using 900 mL of 0.1 M hydrochloric acid with pepsin and FaSSGF at pH 1.6 can be used to compare formulations; a development dissolution target of ≥ 75% release at 45 min is a common starting gate but must be justified by in vivo data rather than assumed from compendial limits. Co-administration of P-gp inhibitors is not a formulation claim for the API; operational boundaries include avoidance of surfactants such as polysorbate 80 at concentrations above 1–2% w/w unless justified by compatibility and dissolution experiments. For oral solid dosage forms, the terminal product must comply with ICH Q3B for degradation products and ICH Q3D for elemental impurities; the patient safety risk from residual anthracycline aglycone impurities is the primary limit on formulation shelf life. Because no commercially established oral reference product has defined a universal dissolution specification, any internal specification must be established through a link to clinical pharmacokinetic data or a qualified in vitro-in vivo relationship.
Within secondary manufacturing suites, idarubicin HCl is classified as an antineoplastic hazardous drug under NIOSH and must be handled in accordance with USP <800>. Facility design for oral solid and injectable processing of idarubicin HCl requires negative room pressure, HEPA-filtered exhaust, and closed-transfer systems because the compound binds to DNA and is teratogenic at low occupational exposure levels. Granule milling, blending, and capsule filling are conducted in isolators or split butterfly valve systems to keep the 8-hour time-weighted average exposure below the internal occupational exposure limit, which for anthracyclines is frequently set in the 0.001 mg/m³ range; published OEL data for idarubicin specifically is limited, so the limit should be derived through an internal occupational toxicology assessment per ICH Q9. Cleaning validation must quantify residues of idarubicin HCl on product contact surfaces by HPLC-MS/MS; an acceptable residue limit is calculated using the health-based exposure limit approach. Swab recovery studies are performed on stainless steel, PTFE, and EPDM equipment surfaces with spiked concentrations of 0.1–1.0 μg/cm²; recovery factors below 70% require correction of the analytical result or re-cleaning. The terminal product quality is supported by environmental monitoring under ISO 14644-1:2015 for viable and non-viable particulates, and by operator medical surveillance per local hazardous drug regulations. Cross-contamination limits for non-cytotoxic products manufactured in shared facilities are set using the permitted daily exposure formula from ICH Q3D and the health-based exposure limit concept in EMA/CHMP/CVMP/543861/2019. Confinement of idarubicin processing to dedicated equipment or appropriate closed systems is the default operational boundary when cleaning validation cannot consistently achieve the PDE-derived limit.
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Idarubicin Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is supplied as idarubicin hydrochloride, the 4-demethoxy congener of daunorubicin, with molecular formula C26H27NO9·HCl and a formula weight of 533.95 g/mol (CAS 57852-57-0). The solid-state form is an orange-red crystalline powder intended for oral solid-dose and injectable cytotoxic dosage units. Compendial-grade material is controlled at release for identity, assay, related substances, residual solvents, water content, and—where parenteral processing is indicated—bacterial endotoxins. The absence of the C4 methoxy group distinguishes the compound from doxorubicin and elevates lipophilicity relative to C4-methoxy anthracyclines, a property that imposes stricter control of particle size and dissolution during oral solid-dose manufacture. Batch-to-batch control therefore requires a dual specification approach: oral grades are released on particle size, polymorphic consistency, and blendability; injectable grades are released on endotoxin, bioburden, and reconstitution-critical solid-state properties.
Release specifications for this API follow the monograph structure of Ph. Eur. and USP where applicable, supplemented by ICH Q6A decision trees for unspecified impurities and residual solvent class limits. A representative panel for a dual-grade lot destined to tablet, capsule, granule, and injectable processing would include reversed-phase HPLC assay with ultraviolet detection, impurity profiling by area normalization, Karl Fischer water determination, residual solvent analysis by headspace gas chromatography, and endotoxin testing for the injectable grade. Because idarubicin is a cytotoxic API, some sponsors apply tighter genotoxic impurity control when process-related intermediates are present. The product code distinction within the Idarubicin Pharma Grade line typically separates the oral solid–grade release specification from the injectable-grade release specification at the particle-size and endotoxin test points.
| Test attribute | Acceptance criterion | Method / compendial reference |
|---|---|---|
| Appearance | orange-red crystalline powder | visual, Ph. Eur. 2.2.1 |
| Identification | IR spectrum matches reference standard; HPLC retention time agrees with reference | Ph. Eur. 2.2.24, USP <621> |
| Assay (dried basis) | 98.0% to 102.0% w/w | HPLC, USP <621> |
| Total related substances | ≤1.0% | HPLC area normalization |
| Water content | ≤0.5% | Karl Fischer, USP <921> |
| Residual solvents | conforms to USP <467> Option 1 | GC-HS |
| Bacterial endotoxins (injectable grade) | ≤0.5 EU/mg | USP <85>, Ph. Eur. 2.6.14 |
| Sterility (if sterile API grade) | conforms | USP <71>, Ph. Eur. 2.6.1 |
| Particle size (injectable grade) | D90 controlled by laser diffraction | ISO 13320:2020 |
The acceptance values shown are illustrative compendial alignment points; the current monograph and the individual certificate of analysis must be confirmed for each manufacturer lot. Analytical method transfer between API manufacturer and dosage-form manufacturer is typically aligned with USP <1224> or equivalent compendial analytical transfer guidance. HPLC system suitability criteria should include resolution between idarubicin and the nearest specified impurity peak of not less than 1.5, tailing factor between 0.8 and 1.5, and injection repeatability below 1.0% RSD for the assay solution.
Water content is critical for both oral and injectable processing. The injectable lyophilization cake is not the same as the API powder; however, residual moisture in the API is controlled to a low limit because free water accelerates glycosidic hydrolysis. Polymorphic consistency is assessed by X-ray powder diffraction or differential scanning calorimetry, and the API should remain within a single crystalline phase unless amorphous content is deliberate and controlled. Residual solvent class limits follow ICH Q3C; solvents such as methanol, dichloromethane, and acetone are evaluated by headspace gas chromatography with flame-ionization or mass-spectrometric detection.
For tablet and capsule processing, particle-size distribution is matched to the chosen granulation route. Wet granulation in high-shear or low-shear mixers is preferred over direct compression when the API content is low and blend uniformity limits are tight; the cytotoxic nature of the compound also requires closed transfer systems and validated cleaning per ICH Q7. Powder flow is characterized by bulk density and tapped density according to USP <616>, with Carr index and Hausner ratio used to select filler rotation speed and compression force. For tableting, roller-compacted dry granulation may be used where water contact must be minimized; however, the anthracycline aglycone is subject to acid-catalyzed and photolytic degradation, so wet granulation fluids should be screened for pH and residual peroxide content. Milling and jet micronization can introduce amorphous content that accelerates hydrolysis; the amorphous fraction should be quantified by X-ray powder diffraction or differential scanning calorimetry and capped by specification.
Direct compression is usually unsuitable for low-dose cytotoxic tablets because segregation and content uniformity risk rise sharply when the drug load falls below approximately 5% w/w; published data for idarubicin-specific direct compression formulations is limited. A pre-blend with a carrier such as lactose monohydrate or microcrystalline cellulose is prepared in a bin blender, followed by roller compaction and screen milling. Tableting is then performed on a rotary press with a target hardness appropriate for immediate release; process ranges should be established by compaction simulation, not by simple press scale-up. Capsule filling on an automated dosator or tamping machine requires control of powder bed height and tamping force to maintain fill weight variability below 3% RSD for a low-dose cytotoxic capsule. Because the compound is light-sensitive, granulation and compression suites may require sodium-vapour or low-UV lighting, and standard white fluorescent lamps should be risk-assessed.
Granule dosage forms require residual moisture control tied to degradation rate data. Fluid-bed granulation parameters such as inlet air temperature, spray rate, and atomization pressure are selected to avoid droplet overwetting and localized acidic microenvironment formation. Blend uniformity and content uniformity for high-potency low-dose tablets and capsules are determined per USP <905>, with the acceptance value controlled at a maximum of 15. Dissolution testing of oral dosage forms uses USP <711> apparatus 2 at 50–75 rpm or apparatus 4 flow-through cells; media in the pH range 1.2–4.5 reflect gastric fluid and acidic stability. Published data for specific idarubicin capsule and tablet formulations is limited; formulators should rely on empirical solubility screening under ICH Q1A(R2) storage conditions.
Formulation route differences between oral and injectable presentations are not solely a matter of particle size. The injectable route imposes a bacterial endotoxin limit, a bioburden specification, and a dissolution-free clarity requirement; the oral route imposes a dissolution specification and a tabletability or capsule-filling profile. These requirements can conflict when a single physical grade is used for both routes. A milling step optimized for injectable solubility may produce excessive fines that impair powder flow during capsule filling; a granulated oral blend may mask a crystal habit change that would reduce injectable dissolution. For this reason, the API is usually split into separate material codes at the particle control step, with the oral grade receiving less aggressive micronization and the injectable grade receiving jet milling or equivalent size reduction under nitrogen.
Injectable idarubicin hydrochloride is commonly processed as a sterile lyophilized cake because the drug undergoes aqueous degradation under terminal moist-heat sterilization. Aseptic processing is therefore employed rather than terminal sterilization; the bulk solution is passed through a 0.22 µm sterilizing filter and filled under EU GMP Annex 1. The formulation vehicle is adjusted below pH 5.0 to maintain solubility and reduce free-base precipitation risk; osmolality is adjusted with sodium chloride or dextrose toward a target of 300 mOsm/kg for physiological compatibility. Tubular or moulded glass vials should comply with USP <660> / Ph. Eur. 3.2.1, and elastomeric closures with USP <381> / Ph. Eur. 3.2.9. Container closure integrity is evaluated under USP <1207> after lyophilization and during stability.
Freeze-drying cycle development should include freeze-dry microscopy and differential scanning calorimetry to establish collapse temperature and the glass transition of the maximally freeze-concentrated solute. Chamber pressure is typically maintained in the 50–150 µbar range, and product temperature must remain below collapse temperature during primary drying. Freezing at −45 °C or below is often required to ensure complete crystallization of the aqueous cosolvent system. If mannitol is used as a bulking agent, annealing at −10 °C to −20 °C can improve crystalline uniformity. Published data for idarubicin-specific lyophilization cycle design is limited, so each container closure and fill volume requires empirical mapping.
Filter compatibility studies should include bubble point integrity testing and product-adsorption screening; PVDF and PES membranes are commonly screened. The bulk solution hold time should be defined at 2–8 °C before filtration and validated by bioburden and impurity data. After lyophilization, residual moisture in the cake is a finished-product attribute controlled by Karl Fischer, and reconstitution time is a critical quality attribute that depends on cake structure, headspace oxygen, and storage temperature. The API itself is not expected to be sterile in routine commerce; sterility is conferred during aseptic filling, so the API supplier must provide a bioburden and endotoxin certificate for injectable-grade lots.
The anthracycline tetracyclic ring system creates specific processing restrictions. The C7 glycosidic bond is susceptible to acid hydrolysis below pH 2.0; the upper aqueous processing limit is set near pH 6.0 because the less-soluble free base may precipitate. The C12 ketone and adjacent phenolic oxygens are metal-chelating sites that form colored complexes with iron and copper ions, so stainless steel contact during acidic aqueous processing should be minimized and trace iron or copper in excipients excluded. Oxidative degradation under atmospheric oxygen is controlled by nitrogen overlay during bulk solution preparation and by vacuum stoppering after lyophilization. Photolability at wavelengths below 420 nm requires amber glass packaging and light-protective handling. Photostability testing is conducted under ICH Q1B to confirm that the container-closure system restricts transmission below this threshold.
Forced degradation studies under acid, base, oxidative, thermolytic, and photolytic conditions are performed per ICH Q1A(R2) and Q1B to identify degradation products and demonstrate stability-indicating methods. The glycosidic bond is most labile below pH 2.0; base stress above pH 8.0 degrades the anthracycline chromophore. Oxidation stress is typically screened with dilute hydrogen peroxide, but no tolerance limit applies to the API without method-specific validation. Processing windows near these limits are narrow; a change of 0.5 pH units at the lower boundary can measurably increase degradation rate and should be controlled by in-process pH verification.
Relative to doxorubicin hydrochloride (molecular formula C27H29NO11·HCl, formula weight 579.98 g/mol, CAS 25316-40-9) and epirubicin hydrochloride (same formula, CAS 56390-09-1), idarubicin hydrochloride has a lower formula weight and higher lipophilicity. This difference stems from the C4 demethoxy substitution and alters the API’s distribution between aqueous and lipid phases in both capsule formulations and injectable co-solvent systems. In tablet and capsule development, the more lipophilic idarubicin may require higher surfactant-to-drug ratios in lipid-based capsules or co-solvent systems in injectables, but idarubicin-specific solubility data under compendial dissolution media remain limited and should be generated experimentally under ICH Q1A(R2) storage conditions. Unlike doxorubicin, which is predominantly presented as an injection, idarubicin is processed into oral capsule, tablet, and granule dosage forms as well as injection, requiring separate compatibility studies for each route.
| Attribute | Idarubicin HCl | Doxorubicin HCl | Epirubicin HCl | Daunorubicin HCl |
|---|---|---|---|---|
| Structural difference | 4-demethoxy | 4-methoxy | 4-methoxy, 4'-epimer | 4-methoxy |
| Molecular formula | C26H27NO9·HCl | C27H29NO11·HCl | C27H29NO11·HCl | C27H29NO10·HCl |
| Formula weight | 533.95 g/mol | 579.98 g/mol | 579.98 g/mol | 563.99 g/mol |
| CAS number | 57852-57-0 | 25316-40-9 | 56390-09-1 | 23541-50-6 |
| Relevant oral solid presentations | capsule, tablet, granule | not routinely oral | not routinely oral | not routinely oral |
| Injectable presentation | lyophilized or solution | lyophilized or solution | lyophilized or solution | lyophilized or solution |
| Relative lipophilicity | higher than C4-methoxy analogs | lower than idarubicin | lower than idarubicin | lower than idarubicin |
Because idarubicin is a narrow-therapeutic-index cytotoxic, differences in lipophilicity and oral absorption are not handled by simple tablet dilution alone; formulation composition must be developed under a quality-by-design framework with physiologically based solubility constraints. Quantitative log P data for idarubicin under standardized shake-flask or reversed-phase HPLC conditions are not assigned as a monograph specification; therefore any formulation decision based on lipophilicity must be anchored to experimentally derived log D or PAMPA permeability values. Comparative impurity profiling between idarubicin and daunorubicin is relevant because the two compounds share the same tetracyclic ring but differ at the C4 position; however, the monographs treat them as separate active substances with separate reference standards and system suitability resolutions. UV detection at 254 nm is typical for related substances, but specificity is confirmed by peak purity analysis using photodiode array detection or high-resolution mass spectrometry.
Because idarubicin hydrochloride is a cytotoxic anthracycline, containment is specified by occupational exposure controls and validated by wipe sampling with analytical methods having a reporting limit derived from the site-specific permissible daily exposure. Transfer should occur in negative-pressure isolators with split butterfly valves; open handling is restricted to HEPA-filtered barriers. The API is normally packed in double LDPE bags inside an aluminum composite foil bag, with a desiccant, and stored at 2–8 °C protected from light. Storage at room temperature may be permitted for short shipment intervals only when thermal stability data generated under ICH Q1A(R2) support the excursion. Incompatibilities include alkaline aqueous solutions, strong oxidizing agents, and iron or copper salts; contact with these species should be excluded from manufacture and cleaning because they accelerate degradation or precipitate the free base. Cleaning validation for oral and injectable lines should follow ICH Q7 and include swab and rinse limits derived from health-based exposure limits.
Stability data should include long-term storage at 2–8 °C for the assigned shelf life, accelerated conditions at 25 °C/60% RH for 6 months, and, where applicable, photostability per ICH Q1B. The API should be protected from repeated freeze-thaw if stored as a solution; however, the solid powder is not normally frozen. Handling under nitrogen or vacuum is acceptable when the container is briefly opened in a controlled isolator, but compressed air should be avoided because oxygen and moisture accelerate degradation.
