Fulvestrant Pharmaceutical Composition Ethanol Reduction
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Solution Overview
Problem
Pharmaceutical preparations containing fulvestrant face challenges due to poor solubility in water and allergic reactions to ethanol, leading to limited patient applicability and instability at low temperatures, particularly with high ethanol concentrations and lack of compatibility among ingredients.
Innovation Solution
A pharmaceutical composition comprising fulvestrant, propylene glycol or 1,3-butylene glycol, benzyl alcohol, benzyl benzoate, and castor oil, with ethanol content less than 1% by mass, ensuring good dissolution properties and compatibility, thereby preventing turbidity and allowing administration to ethanol-sensitive patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If ethanol is used as a solvent to achieve high fulvestrant concentration, then dissolution properties are improved, but allergic reactions occur in ethanol-sensitive patients
Solution Approach 1:
The patent changes the solvent composition parameters by reducing ethanol content from high concentration (typically 50-70% in conventional formulations) to less than 1% by mass, while adjusting the proportions of alternative solvents (propylene glycol, 1,3-butylene glycol, benzyl alcohol, benzyl benzoate, and castor oil) to maintain fulvestrant solubility and therapeutic efficacy
Solution Approach 2:
The patent employs a composite solvent system combining multiple solvents (propylene glycol, 1,3-butylene glycol, benzyl alcohol, benzyl benzoate, and castor oil) with complementary properties to achieve both high fulvestrant solubility and compatibility with ethanol-sensitive patients, replacing the single-ethanol solvent system
2Object-affected harmful factors
If castor oil is excluded from the formulation, then allergic reaction risk is reduced, but therapeutic efficacy and stability are compromised
Solution Approach 1:
The patent adjusts the concentration parameter of castor oil to a specific range (0.1-20% by mass) that balances its beneficial effects on fulvestrant solubility and therapeutic efficacy against potential allergic reactions, optimizing the risk-benefit ratio
3Quantity of substance
If high ethanol concentration is used to ensure dissolution, then fulvestrant solubility is improved, but compatibility among ingredients deteriorates at low temperatures
Solution Approach 1:
The patent changes the temperature-stability parameter by selecting solvents with appropriate freezing points and compatibility characteristics (propylene glycol, 1,3-butylene glycol, benzyl alcohol, benzyl benzoate, and castor oil) that maintain ingredient compatibility and prevent precipitation or phase separation at low storage temperatures, unlike high-ethanol formulations
Solution Approach 2:
The patent uses a composite solvent system where each component contributes specific properties: propylene glycol and 1,3-butylene glycol provide low-temperature fluidity and solubility, benzyl alcohol and benzyl benzoate enhance fulvestrant dissolution, and castor oil ensures stability and compatibility, collectively preventing low-temperature instability
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 achieves high fulvestrant concentration with improved stability and compatibility, allowing effective administration to a broader patient range while maintaining therapeutic efficacy and preventing compositional changes due to ethanol volatilization.
Implementation Method 1
fulvestrant, propylene glycol or 1,3-butylene glycol, benzyl alcohol, benzyl benzoate, and castor oil... ensures good dissolution properties
Implementation Method 2
occurrence of turbidity is suppressed in a case of being stored at a low temperature
Data Source
AI summary
Provided is a pharmaceutical composition which contains fulvestrant in an amount of 4.5% by mass to 10.0% by mass with respect to the entire mass of the pharmaceutical composition, at least one kind of polyhydric alcohol selected from propylene glycol or 1,3-butylene glycol in an amount of 8% by mass to 23% by mass with respect to the entire mass of the pharmaceutical composition, benzyl alcohol in an amount of 5% by mass to 24% by mass with respect to the entire mass of the pharmaceutical composition, benzyl benzoate in an amount of 8% by mass to 19% by mass with respect to the entire mass of the pharmaceutical composition, and castor oil, and in which a content of ethanol is less than 1% by mass with respect to the entire mass of the pharmaceutical composition, and a content of benzoic acid is less than 1% by mass with respect to the entire mass of the pharmaceutical composition.