Fulvestrant Composition Without Ester Solvents for Room-Temperature Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing fulvestrant formulations require refrigeration for storage stability and contain non-aqueous ester solvents, which are not suitable for long-term storage at room temperature and have limitations in solubility and stability.
Innovation Solution
A composition comprising fulvestrant, a pharmaceutically acceptable alcohol, polysorbate 80, and castor oil, which is storage stable at various temperatures and enhances solubility without non-aqueous ester solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If non-aqueous ester solvents (e.g., benzyl benzoate) are used to solubilize fulvestrant at high concentrations, then solubility is improved, but storage stability at room temperature deteriorates and refrigeration is required
Solution Approach 1:
The patent changes the chemical composition parameters by replacing non-aqueous ester solvents with aqueous-based cosolvent systems (polyethylene glycol, propylene glycol, ethanol) and surfactants. This parameter change enables the formulation to achieve both high fulvestrant solubility and room temperature storage stability, resolving the contradiction between solubility enhancement and storage stability.
2Quantity of substance
If non-aqueous ester solvents are used to enhance solubility, then therapeutic efficacy is maintained, but the formulation complexity and storage requirements increase
Solution Approach 1:
The patent employs a composite cosolvent system combining multiple components (polyethylene glycol, propylene glycol, ethanol, and surfactants like polysorbate 80 or cremophor EL). This composite approach achieves high fulvestrant solubility while maintaining formulation stability and simplifying storage requirements, as the aqueous-based composite system is inherently more stable and easier to store than formulations containing non-aqueous ester solvents.
3Duration of action of moving object
If high concentrations of fulvestrant are formulated, then dosing frequency can be reduced, but solubility limitations prevent achieving therapeutic concentrations
Solution Approach 1:
The patent introduces cosolvents (polyethylene glycol, propylene glycol, ethanol) and surfactants (polysorbate 80, cremophor EL) as intermediary substances that facilitate the solubilization of fulvestrant. These intermediaries enable the formulation to achieve high fulvestrant concentrations (50-100 mg/mL) by mediating between the lipophilic drug molecule and the aqueous-based vehicle, thereby allowing reduced dosing frequency while maintaining therapeutic efficacy.
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 provides stability and solubility comparable to formulations with ester solvents, maintaining therapeutic efficacy and pharmacokinetics, while allowing storage at room temperature.
Implementation Method 1
the introduction of a non-aqueous ester solvent which is miscible in castor oil and an alcohol surprisingly eases the solubilization of fulvestrant into a concentration of at least 50 mg/mL
Implementation Method 2
U.S. Patent Application Publication 2004/0175402 discloses a formulation adapted for administration by injection containing fulvestrant in a ricinoleate vehicle comprising an antioxidant, such as thiourea, to suppress the formation of fulvestrant oxidative degradation products and improve formulation stability
Data Source
AI summary
The invention provides a fulvestrant composition comprising a pharmaceutically acceptable vehicle and not more than 2% total impurities and which, optionally, is free of a non-aqueous ester solvent. The composition may be used to treat hormone receptor positive metastatic breast cancer in a subject.