Cyclodextrin Injectable Composition for Solubility and Stability
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Solution Overview
Problem
Conventional liquid pharmaceutical compositions of 1-(5-(2,4-difluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine require excessive amounts of solubilizers and organic solvents, leading to hypersensitivity issues and stability concerns, necessitating the development of a formulation with improved solubility and stability without these components.
Innovation Solution
A liquid pharmaceutical composition comprising 1-(5-(2,4-difluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine, or a pharmaceutically acceptable salt thereof, is formulated with beta-cyclodextrin as a stabilizer and D-mannitol as a bulking agent for freeze-drying, along with distilled water or physiological saline as a solvent, to enhance solubility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If excessive amounts of solubilizers and organic solvents are used to dissolve the compound with low water solubility, then solubility is improved, but hypersensitivity occurs and stability deteriorates
Solution Approach 1:
The patent removes harmful solubilizers and organic solvents from the formulation, extracting only the essential components needed for solubility enhancement. The invention uses minimal amounts of specific solubilizers (polysorbate 80, polysorbate 20, or poloxamer 188) combined with cyclodextrin, eliminating the need for excessive amounts of traditional solubilizers that cause hypersensitivity.
Solution Approach 2:
The patent introduces cyclodextrin as an intermediary substance that enhances solubility through inclusion complex formation. Cyclodextrin acts as a mediator between the poorly soluble compound and the aqueous environment, forming stable inclusion complexes that improve solubility without requiring excessive solubilizers or organic solvents.
2Quantity of substance
If excessive amounts of solubilizers and organic solvents are used to dissolve the compound with low water solubility, then solubility is improved, but stability deteriorates
Solution Approach 1:
The patent removes harmful solubilizers and organic solvents from the formulation, extracting only the essential components needed for solubility enhancement. The invention uses minimal amounts of specific solubilizers (polysorbate 80, polysorbate 20, or poloxamer 188) combined with cyclodextrin, eliminating the need for excessive amounts of traditional solubilizers that cause hypersensitivity.
Solution Approach 2:
The patent introduces cyclodextrin as an intermediary substance that enhances solubility through inclusion complex formation. Cyclodextrin acts as a mediator between the poorly soluble compound and the aqueous environment, forming stable inclusion complexes that improve solubility without requiring excessive solubilizers or organic solvents.
3Quantity of substance
If conventional solubilizers (ethanol, polysorbate) are used to improve solubility, then solubility is improved, but harmful effects on the human body occur
Solution Approach 1:
The patent employs cyclodextrin, a naturally occurring carbohydrate derivative, as a temporary solubility enhancer that is metabolized and excreted safely. Cyclodextrin forms inclusion complexes with the drug compound, enhancing solubility without accumulating harmful effects in the body, and is eliminated through normal metabolic processes.
Solution Approach 2:
The patent changes the chemical parameters of the formulation by using cyclodextrin inclusion complexes instead of traditional organic solvent-based solubilization. This parameter change involves switching from hydrophobic solubilization mechanisms to hydrophilic inclusion complex formation, fundamentally altering how the compound is dissolved and administered.
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 excellent solubility and stability, minimizing hypersensitivity risks and maintaining long-term storage integrity, suitable for injectable use.
Implementation Method 1
the cyclodextrin is beta-cyclodextrin, or gamma-cyclodextrin, the cyclodextrin is contained in an amount of 3.0 to 25.0 parts by weight based on 1 part by weight of the compound
Implementation Method 2
the bulking agent for freeze-drying is D-mannitol, sucrose, sorbitol, or trehalose, the bulking agent for freeze-drying is contained in an amount of 3.0 to 25.0 parts by weight based on 1 part by weight of the compound
Data Source
AI summary
The present invention can be usefully used as a liquid pharmaceutical composition of 1-(5-(2,4-difluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine, or a pharmaceutically acceptable salt thereof.