Stabilizing N-butylidenephthalide in Pharmaceutical Formulations
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Solution Overview
Problem
N-butylidenephthalide, a potential treatment for malignant brain tumors, is hydrophobic and not soluble in water, limiting its use in pharmaceutical formulations and clinical applications due to stability issues, which affects its bioavailability and delivery.
Innovation Solution
A pharmaceutical composition is developed using a medium system comprising phosphate buffered saline, vegetable or animal oils, and a combination of polyethylene glycol and dimethyl sulfoxide, which stabilizes n-butylidenephthalide, enhancing its solubility and bioavailability for intranasal administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If n-butylidenephthalide is used as a hydrophobic compound, then it has potential therapeutic effect for malignant brain tumors, but it is not soluble in water which limits its pharmaceutical formulation and clinical applications
Solution Approach 1:
The patent uses a medium system comprising phosphate buffered saline, vegetable or animal oils, and a combination of polyethylene glycol and dimethyl sulfoxide as an intermediary to bridge the hydrophobic n-butylidenephthalide and the aqueous environment required for pharmaceutical formulation. This medium system enables the hydrophobic compound to be stabilized and delivered effectively without compromising its therapeutic activity.
Solution Approach 2:
The patent changes the physical and chemical parameters of the formulation by using a specialized medium system that alters the solubility characteristics of n-butylidenephthalide. The combination of polyethylene glycol and dimethyl sulfoxide in the medium system modifies the solvent properties, enabling the hydrophobic compound to achieve adequate solubility and stability for intranasal administration.
2Reliability
If n-butylidenephthalide is administered in high concentrations to ensure therapeutic effect, then it can overcome solubility limitations, but it increases toxic side effects
Solution Approach 1:
The medium system acts as a mediator that enables effective delivery of n-butylidenephthalide at lower concentrations. By improving solubility and stability through the phosphate buffered saline, vegetable or animal oils, and polyethylene glycol-dimethyl sulfoxide combination, the formulation achieves therapeutic efficacy without requiring high drug concentrations that would cause toxic side effects.
Solution Approach 2:
The patent optimizes the concentration parameter by using a specialized medium system that enhances drug delivery efficiency. This allows the formulation to achieve therapeutic effects at lower concentrations, thereby reducing toxic side effects while maintaining reliability of treatment.
3Duration of action of stationary object
If n-butylidenephthalide is stored for long-term use, then it provides sustained treatment capability, but it loses stability and activity due to hydrophobic properties
Solution Approach 1:
The medium system serves as a stabilizing intermediary that protects n-butylidenephthalide during long-term storage. The phosphate buffered saline, vegetable or animal oils, and polyethylene glycol-dimethyl sulfoxide combination creates a stable environment that maintains drug activity over time, preventing degradation that would otherwise occur due to the compound's hydrophobic properties.
Solution Approach 2:
The patent stabilizes the drug composition parameter through the specialized medium system. This formulation approach maintains the stability of n-butylidenephthalide during long-term storage by using components that prevent degradation, thereby enabling sustained treatment capability while preserving drug activity.
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 maintains n-butylidenephthalide's activity over long-term storage, reduces side effects, and allows for precise dosing, achieving effective therapeutic outcomes with lower concentrations, thereby improving treatment efficacy for malignant brain tumors.
Implementation Method 1
a medium system, comprising a first ingredient, a second ingredient and a third ingredient, wherein the first ingredient is a phosphate buffered saline, the second ingredient is selected from the group consisting of vegetable oils, animal oils, fatty acids and combinations thereof, and the third ingredient is a combination of polyethylene glycol and dimethyl sulfoxide (DMSO)
Data Source
Figure 1A
Figure 1B~1C
Figure 2A~2B
AI summary
A stable pharmaceutical composition, containing: (a) a medium system, containing a first component, a second component, and a third component, wherein the first component is a phosphate buffer solution; the second component is selected from the group consisting of: vegetable oils, animal oils, fatty acids and a combination thereof; and the third component is selected from the group consisting of: polyethylene glycol, dimethyl sulfoxide, ethanol, polypropylene glycol, polysorbate, polyoxyethylated vegetable oil, ethyl acetate, hydroxyethyl 12-hydroxy stearate, vitamin E, polyethylene glycol succinate, and a combination thereof, and (b) n-butylidenephthalide (BP).