Ethanol-Free Nimodipine Composition for Moist Heat Sterilization
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Solution Overview
Problem
Current nimodipine injections contain high levels of ethanol, causing vascular irritation and other adverse effects, and are prone to impurity formation, particularly Impurity I, which poses safety risks and stability issues during infusion.
Innovation Solution
A nimodipine composition free of ethanol and phospholipids, using a non-phospholipid surfactant and a co-solvent, such as propylene glycol, is prepared through moist heat sterilization, ensuring stability and solubility, and can be diluted with aqueous vehicles for administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If ethanol is used as a solvent to dissolve nimodipine, then the solubility of nimodipine is improved, but vascular irritation and adverse effects increase
Solution Approach 1:
The patent removes ethanol from the formulation entirely, extracting the harmful solvent while maintaining nimodipine solubility through alternative means (non-phospholipid surfactants and co-solvents), thereby eliminating vascular irritation and adverse effects associated with ethanol
Solution Approach 2:
The patent introduces non-phospholipid surfactants and co-solvents as intermediary substances that facilitate nimodipine dissolution without the harmful effects of ethanol, serving as mediators between the drug and the aqueous environment
2Stability of the object's composition
If phospholipids are used in the formulation, then the stability of nimodipine is improved, but impurity formation increases
Solution Approach 1:
The patent removes phospholipids from the formulation, extracting the source of impurity formation while maintaining stability through alternative stabilizing agents, thereby eliminating the generation of harmful impurities like Impurity I
Solution Approach 2:
The patent introduces non-phospholipid surfactants as intermediary stabilizing agents that provide formulation stability without promoting impurity formation, replacing phospholipids as the stability-maintaining component
3Reliability
If ethanol-containing formulation is administered, then the therapeutic effect is achieved, but disulfiram-like adverse reactions occur
Solution Approach 1:
The patent removes ethanol from the formulation, extracting the cause of disulfiram-like reactions while preserving the therapeutic effect of nimodipine, thereby eliminating the risk of adverse reactions when combined with cephalosporins or nitroimidazoles
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 a stable, homogenous solution that avoids ethanol-related adverse effects, reduces impurity formation, and allows for easy administration without specialized infusion sets, enhancing safety and convenience.
Implementation Method 1
a non-phospholipid surfactant selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyl 15 hydroxystearate, D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), polysorbates, glyceryl monocaprylocaprate
Implementation Method 2
a co-solvent, which is propylene glycol
Implementation Method 3
the composition is terminally sterilized by moist heat sterilization
Data Source
AI summary
Provided are a moist-heat sterilized nimodipine composition free of ethanol and phospholipid and a method for preparing the same. The composition comprises (1) nimodipine; (2) a non-phospholipid surfactant selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyl 15 hydroxystearate, D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), polysorbates, glyceryl monocaprylocaprate, or any mixture of two or more thereof; and (3) a co-solvent, which is propylene glycol.