Remifentanil Injection Stability via Composite Solvent

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Solution Overview

Problem

Current remifentanil injection solutions are unstable during long-term storage and require a complicated two-stage preparation process, which increases the risk of medication errors and storage instability.

Innovation Solution

A remifentanil injection solution formulation is developed that includes remifentanil and/or its physiologically acceptable salts, water, and a stabilizer like polyethylene glycol, with specific ratios to ensure stability and prevent denaturation, allowing for a one-step preparation and long-term storage stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If remifentanil is formulated as an aqueous injection solution, then ease of operation and solubility are improved, but storage stability deteriorates

Engineering Contradiction:
Improveease of injection solution preparationVSAvoidstorage stability of remifentanil solution
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent uses a composite solvent system comprising water and a non-aqueous solvent (such as ethanol, propylene glycol, or polyethylene glycol) in specific proportions. This composite formulation allows remifentanil to remain soluble while significantly improving storage stability, resolving the contradiction between ease of preparation and storage stability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent optimizes the concentration of remifentanil and the ratio of water to non-aqueous solvent within specific ranges. By controlling these parameters, the formulation achieves both good solubility for easy preparation and enhanced storage stability, preventing the deterioration that occurs in pure aqueous solutions.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If lyophilized remifentanil powder is reconstituted with a large amount of water, then sufficient dissolution is achieved, but internal pressure rises causing solution leakage

Engineering Contradiction:
Improvedissolution completeness of remifentanilVSAvoidsolution leakage from container
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent formulates remifentanil injection solutions with optimized concentrations and solvent compositions that allow complete dissolution without generating excessive internal pressure. This prevents container leakage while ensuring sufficient dissolution of the active ingredient.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If a two-stage preparation process is used to prepare remifentanil injection solution, then concentration control is improved, but device complexity and risk of medication errors increase

Engineering Contradiction:
Improveconcentration accuracy of remifentanilVSAvoidcomplexity of preparation process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent provides pre-formulated remifentanil injection solutions with precisely controlled concentrations manufactured in advance. This merges the dissolution and concentration control steps into a single ready-to-use product, eliminating the complex two-stage preparation process and reducing medication errors while maintaining concentration accuracy.

Inventive Principle:
Principle #5Merging (Combining)

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 formulation maintains a high survival rate of remifentanil, preventing denaturation and precipitation, enabling easy one-step preparation of the final injection solution at the anesthetic site, thus enhancing storage stability and reducing the risk of medication errors.

Implementation Method 1

a stabilizer, said stabilizer being polyethylene glycol or propylene glycol

Methodology Applied
Scientific EffectStabilization: Preservative

Implementation Method 2

containing remifentanil and/or physiologically acceptable salts thereof, water

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentEP3192509B1Remifentanil injection
Publication Date: 2021.03.31 TERUMO KK

AI summary

A remifentanil injection solution formulation contains remifentanil and/or physiologically acceptable salts thereof, water, and a stabilizer, the remifentanil injection solution formulation contains said water at a rate of 0.007 to 0.025mL per 1mg of said remifentanil.