Nimodipine Injection Emulsion Without Ethanol or Tween 80
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Solution Overview
Problem
Nimodipine injections face challenges due to low solubility in water, high liver first-pass effect, frequent administration requirements, skin and blood vessel irritation from ethanol solubilization, crystallization issues, and adverse reactions from cosolvents like Tween 80 and benzyl alcohol, leading to poor stability and safety concerns.
Innovation Solution
A nimodipine injection composition using α-type nimodipine, soya lecithin or egg yolk lecithin as emulsifiers, calcium disodium edetate as a complexing agent, and glycerol as an osmotic pressure adjusting agent, formulated without ethanol or benzyl alcohol, achieving stable emulsions with improved solubility, stability, and reduced toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high-concentration ethanol is used for solubilization, then solubility of nimodipine is improved, but skin and blood vessel irritation increases
Solution Approach 1:
The patent changes the solvent system from ethanol-based to oil-based (soybean oil and medium-chain fatty oil), fundamentally altering the chemical parameter of the solubilizing agent. This substitution maintains solubility while eliminating the irritating effects of ethanol, directly resolving the contradiction between solubility and irritation.
Solution Approach 2:
The patent uses a composite emulsion system combining oil phase (soybean oil and medium-chain fatty oil), emulsifier (soya lecithin or egg yolk lecithin), and aqueous phase. This composite material approach creates a stable formulation that solubilizes nimodipine effectively while avoiding the harmful irritation caused by pure ethanol solutions.
2Object-affected harmful factors
If nimodipine is administered by slow dripping, then blood vessel irritation is reduced, but administration time increases
Solution Approach 1:
The patent changes the fundamental parameter of the vehicle from ethanol to oil-based emulsion. This parameter change allows the drug to be administered without the slow dripping requirement, as the oil-based formulation is inherently less irritating to blood vessels, thus reducing both side effects and administration time simultaneously.
3Quantity of substance
If nimodipine injection is transferred to infusion bottle for mixing, then solubility is maintained, but crystallization occurs
Solution Approach 1:
The patent employs a composite emulsion system with oil phase, emulsifier, and aqueous phase that creates a stable colloidal structure. This composite material prevents crystallization during storage and mixing while maintaining solubility, as the emulsifier stabilizes the oil droplets and prevents drug precipitation.
Solution Approach 2:
The emulsifier (soya lecithin or egg yolk lecithin) acts as an intermediary substance between the oil phase and aqueous phase. This intermediary prevents direct contact between nimodipine and water, stabilizing the formulation and preventing crystallization while maintaining solubility in the oil phase.
4Reliability
If frequent administration is required, then plasma concentration control is improved, but patient convenience decreases
Solution Approach 1:
The oil-based emulsion formulation provides sustained release of nimodipine, creating a continuous therapeutic effect that maintains stable plasma concentrations over an extended period. This continuous action eliminates the need for frequent dosing, improving both plasma concentration control and patient convenience simultaneously.
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 new formulation enhances solubility, stability, and safety by avoiding crystallization and adverse reactions, maintaining effective plasma concentration, and reducing toxicity, with improved clinical applicability.
Implementation Method 1
formulated into a fat emulsion injection
Implementation Method 2
soya lecithin or egg yolk lecithin as emulsifiers
Implementation Method 3
glycerol as an osmotic pressure adjusting agent
Implementation Method 4
calcium disodium edetate as a complexing agent
Data Source
AI summary
Disclosed are a nimodipine injection composition and preparation method therefor. The nimodipine injection composition includes the following components in parts by mass concentration: 0.02-0.23% of nimodipine, 2-30% of oil for injection, 0.8-3% of emulsifier, 0-0.1% of complexing agent, 0-0.3% of stabilizer, 1-3% of osmotic pressure adjusting agent. The composition does not contain solubilizers such as ethanol, auxiliary emulsifiers such as tween-80, and cosolvents such as benzyl alcohol.