Docetaxel

Docetaxel: The Next-Generation Taxane for Advanced Oncology Therapeutics

1. What is Docetaxel?
Docetaxel is a semi-synthetic taxoid antineoplastic agent derived from 10-deacetylbaccatin III (10-DAB) isolated from Taxus baccata needles. As a microtubule-stabilizing taxane, it exhibits 2-fold greater potency than paclitaxel by promoting tubulin assembly and inhibiting depolymerization, leading to mitotic arrest in cancer cells. Approved for metastatic breast, prostate, and NSCLC cancers, its enhanced bioavailability and reduced multidrug resistance make it a first-line chemotherapeutic cornerstone.

2. Source, Chemical Properties & Identification

• Source:

  • Semi-synthesis from 10-DAB (European Yew needles)

  • Plant cell fermentation alternatives emerging

• Chemical Properties:

  Parameter	Specification
  CAS No.	114977-28-5
  MF	C₄₃H₅₃NO₁₄
  MW	807.88 g/mol
  EINECS	601-127-2
  Appearance	White crystalline powder
  Solubility	Ethanol, PEG, polysorbate 80; water-insoluble
  Stability	Light-sensitive; store 2-8°C protected

3. Therapeutic Profile & Safety

• Premium Product Specification:
  Shaanxi Zhonghong delivers >99.3% USP-grade Docetaxel with <0.15% epimer impurities via proprietary chiral separation technology.

• Clinical Efficacy:

  • Metastatic Breast Cancer: 55% response rate (vs. 42% paclitaxel)

  • mCRPC: Survival extension (18.9 vs 16.5 months placebo)

  • NSCLC: 31% 2-year survival in combination regimens

• Dosing Protocol:

  • IV infusion: 75-100 mg/m² over 1 hr q3w

  • Premedication: Dexamethasone 8mg BID (day -1 to +1)

• Critical Safety Monitoring:

  Toxicity	Incidence	Management
  Neutropenia	98% (G4:32%)	G-CSF support
  Fluid Retention	50%	Steroid premedication
  Neuropathy	35-60%	Dose reduction at Grade ≥2
  Hypersensitivity	20%	Premedication + extended infusion

4. Source Manufacturer: Shaanxi Zhonghong Investment Technology Co., Ltd.

Leveraging 28 years of taxane expertise:

• Core Capabilities:

  • Vertical Integration: Controlled Taxus cultivation → 10-DAB extraction → chiral synthesis

  • Proprietary Tech: Enzymatic C-13 side chain coupling (yield >82%)

  • Cutting-Edge QC: Chiral SFC-HPLC, LC-QTOF-MS for stereochemical purity

  • Global Compliance: cGMP certified (US FDA, EDQM)

5. Product Specification & Quality Control

Advanced QC Protocol:
Implementing QbD-driven process controls, Shaanxi Zhonghong conducts in-line PAT monitoring via FT-NIR spectroscopy during crystallization. Raw materials undergo HPLC-ELSD fingerprinting against proprietary taxane libraries. Final products are tested for subvisible particles (HIAC), osmolality (≥280 mOsm/kg), and sterility (membrane filtration). Forced degradation studies (acid/base/oxidative/thermal) establish stability-indicating methods. Lyophilized formulations maintain <0.5% degradation after 24 months at -20°C. All batches include genotoxicity assessment (Ames test) and elemental impurity profiling per ICH Q3D.

6. Production Process

1. Biomass Extraction: Supercritical CO₂ extraction of T. baccata needles

2. 10-DAB Isolation: Centrifugal partition chromatography (CPC) → 98% purity

3. Chiral Synthesis:

   • Enzymatic esterification with protected side chain (patented lipase)

   • Deprotection under hydrogenolysis

4. Purification: Three-step countercurrent chromatography

5. Crystallization: Ethanol/water system with controlled polymorph seeding

6. Lyophilization: Cryoconcentration technology for enhanced reconstitution

7. Clinical & Research Applications

• Oncology:

  • mCRPC (with prednisone)

  • HER2- breast cancer (TAC regimen)

  • NSCLC (platinum combinations)

• Drug Delivery Innovations:

  • Liposomal docetaxel (50% reduced neutropenia)

  • HA-PEI nanocarriers for targeted delivery

• Medical Devices:

  • Drug-eluting biliary stents

8. Packaging & Cold Chain Logistics

• Primary Packaging: Nitrogen-flushed amber vials with fluorotec-coated stoppers

• Configurations: 20mg/80mg single-dose vials

• Storage: 2-8°C protected from light

• Shipping: Validated cold chain (-15 to -25°C) with temperature loggers

• Stability: 36 months when unopened

9. Scientific Frontiers

• Mechanism Advances:

  • ROS-mediated JNK/SAPK pathway activation

  • Immunogenic cell death induction

• Innovations:

  • Oral prodrugs (ModraDoc006/r)

  • PSMA-targeted theranostics

• Supply Challenges:

  • Sustainable yew cultivation (yield: 0.02% 10-DAB)

  • Continuous flow manufacturing scale-up

10. FAQ

Q: Why is docetaxel dosed q3w?
A: Pharmacodynamics show sustained tubulin stabilization for 14-21 days post-infusion.

Q: Managing fluid retention?
A: Dexamethasone 8mg BID reduces incidence from 50% to <7%.

Q: Generic bioequivalence?
A: Shaanxi Zhonghong’s API meets EMA strict equivalence criteria (±3% impurity profile match).

11. Procurement Information

Source cGMP Docetaxel API:

• Email: liaodaohai@gmail.com

• Web: aiherba.com/docetaxel-api

• Capabilities:

  • Custom polymorphs (Form I/II)

  • Tween 80-free formulations

  • DMF/CEP support

12. Conclusion

Docetaxel remains indispensable in modern oncology regimens due to its enhanced pharmacokinetics and broad antitumor spectrum. Shaanxi Zhonghong combines vertically integrated botanical sourcing, enzymatic synthesis technology, and uncompromising QC protocols to deliver APIs exceeding pharmacopeial standards. Partner with our 28-year taxane specialists for secure, sustainable docetaxel supply.

13. References

1. Ringel I & Horwitz SB. J Natl Cancer Inst. 1991;83(4):288-91. (Mechanism)

2. European Pharmacopoeia 11.0: Docetaxel Monograph (01/2023:2253)

3. Tannock IF, et al. NEJM. 2004;351:1502-12. (TAX 327 trial)

4. Zhonghong Tech Report: “Enzymatic C-13 Functionalization” (Patent WO2022/178642)

5. Baker SD, et al. Clin Cancer Res. 2004;10:7617-24. (Pharmacokinetics)

6. FDA Guidance: Docetaxel ANDA Recommendations (2023)