Docetaxel Injection Composition Without Ethanol or Polysorbate
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Solution Overview
Problem
Current docetaxel formulations containing polysorbate 80 and ethanol pose significant adverse effects such as anaphylaxis, irritation, and intoxication, and require complex preparation steps, while ethanol-free formulations are unstable and difficult to achieve high solubility and stability.
Innovation Solution
A docetaxel composition using cyclodextrin, co-solvents (like PEG), stabilizers (such as Poloxamer and povidone), and additives (like citric acid) without ethanol or polysorbate, prepared through methods including high-pressure homogenization, achieving solubility up to 310 mg/mL and stability for over 24 months.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If polysorbate 80 and ethanol are used as solubilizers and diluents, then docetaxel solubility is improved, but adverse effects such as anaphylaxis, irritation, and intoxication occur
Solution Approach 1:
The patent removes ethanol and polysorbate 80 from the formulation and replaces them with cyclodextrin and other safe excipients. This extraction of harmful substances while maintaining the essential solubilization function resolves the contradiction between achieving high solubility and avoiding adverse effects.
Solution Approach 2:
Cyclodextrin serves as an intermediary substance that forms inclusion complexes with docetaxel, enabling solubilization without requiring ethanol or polysorbate 80. This intermediary mechanism allows the patent to maintain docetaxel solubility while eliminating the harmful components.
2Reliability
If ethanol is used in the formulation, then docetaxel solubility and stability are improved, but preparation complexity and risk of intoxication increase
Solution Approach 1:
The patent extracts ethanol from the formulation system and replaces it with cyclodextrin-based solubilization. This eliminates the need for complex ethanol removal steps and reduces preparation complexity while maintaining formulation stability through the inclusion complex mechanism.
3Quantity of substance
If polysorbate 80 is used as a solubilizer, then docetaxel solubility is improved, but anaphylaxis risk increases
Solution Approach 1:
The patent removes polysorbate 80 from the formulation and replaces it with cyclodextrin. This extraction of the allergenic substance eliminates the anaphylaxis risk while maintaining docetaxel solubility through the alternative solubilization mechanism provided by cyclodextrin inclusion complexes.
4Object-affected harmful factors
If ethanol-free formulation is used, then adverse effects are reduced, but solubility and stability deteriorate
Solution Approach 1:
Cyclodextrin acts as an intermediary that enables ethanol-free solubilization by forming inclusion complexes with docetaxel. This intermediary mechanism allows the patent to achieve high solubility without requiring ethanol, thus resolving the contradiction between reducing adverse effects and maintaining solubility.
Solution Approach 2:
The patent changes the solubilization mechanism from ethanol-based to cyclodextrin-based inclusion complex formation. This parameter change in the solubilization approach enables ethanol-free formulation while maintaining docetaxel solubility at clinically relevant concentrations.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition avoids adverse effects, reduces preparation complexity, and ensures long-term stability and high solubility, meeting clinical requirements without ethanol or polysorbate, thus enhancing safety and usability.
Implementation Method 1
The present invention relates to a pharmaceutical composition containing docetaxel and cyclodextrin. The composition comprises: 1 part by weight of docetaxel and 10-100 parts by weight of cyclodextrin.
Implementation Method 2
The steps comprising: (1) adding a liquid medium to a high-pressure homogenization device, (2) adding docetaxel to the liquid medium in the high-pressure homogenization device, (3) homogenizing the docetaxel and the liquid medium in the high-pressure homogenization device under high pressure to disperse and dissolve the docetaxel in the liquid medium
Data Source
AI summary
A docetaxel composition for injection and a preparation method therefor. The composition comprises the following components in parts by weight: 1 part of docetaxel, 20-60 parts of cyclodextrin, 5-80 parts of a solubilizer, 10-20 parts of stabilizer 1, 0.2-30 parts of stabilizer 2, and 0.001-1.0 part of an additive. The composition does not comprise ethanol and polysorbate, and ethanol is not used in the preparation process thereof.