Dexibuprofen Injectable Formulation Stability Optimization

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Solution Overview

Problem

Dexibuprofen, a key pain reliever, faces challenges in formulating stable injectable formulations due to its poor water solubility, and existing formulations with arginine as a solubilizing agent can cause adverse effects when used in high doses, necessitating a balance between solubility and safety.

Innovation Solution

An injectable formulation of dexibuprofen with arginine in the range of 300 to 500 parts by weight, pH 6.5 to 8.5, and an injection container with reduced oxygen levels through nitrogen substitution to ensure stability and safety, preventing precipitation and adverse reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If arginine is used as a solubilizing agent for dexibuprofen, then water solubility is improved, but adverse effects occur when used in high doses

Engineering Contradiction:

Improvewater solubilityVSAvoidadverse effects

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the arginine to dexibuprofen weight ratio to a specific range (3:4 to 5:4) and controls pH within 6.5-8.5, transforming the chemical environment parameters to achieve solubility without excessive arginine dosage, thereby preventing adverse effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite injectable formulation combining dexibuprofen with arginine and additional excipients (sodium chloride, glucose, edetate disodium, etc.) to form a stable pharmaceutical composition that enhances solubility while maintaining safety through balanced composition

Inventive Principle:

Principle #40Composite materials

2Productivity

If dexibuprofen is formulated for injection, then bioavailability is improved, but stability is compromised due to poor water solubility

Engineering Contradiction:

ImprovebioavailabilityVSAvoidformulation stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent adjusts critical parameters including pH (6.5-8.5), arginine concentration (300-500 parts per 400 parts dexibuprofen), and oxygen saturation (≤5%) to simultaneously achieve solubility for injection and stability during storage

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies nitrogen substitution to reduce oxygen saturation in the injection container to 5% or less, creating an inert atmosphere that prevents oxidation and degradation of dexibuprofen, thereby maintaining formulation stability

Inventive Principle:

Principle #39Inert atmosphere (Inert environment)

3Quantity of substance

If arginine content is increased to improve solubility, then dissolution is enhanced, but precipitation of main component occurs

Engineering Contradiction:

ImprovedissolutionVSAvoidprecipitation

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent identifies and controls multiple interacting parameters including pH (6.5-8.5), arginine ratio (300-500:400), and oxygen saturation (≤5%), where the combined optimization of these parameters prevents precipitation while maintaining dissolution

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent establishes specific quantitative ranges for arginine content and pH that serve as feedback control parameters, ensuring the formulation remains within the stable dissolution zone without exceeding thresholds that would trigger precipitation

Inventive Principle:

Principle #23Feedback

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 stability and safety by optimizing arginine content and pH, preventing main component precipitation and ensuring excellent storage stability, reducing the risk of adverse effects associated with arginine overdose.

Implementation Method 1

arginine is used in an amount of 300 to 500 parts by weight, based on 400 parts by weight of dexibuprofen

Methodology Applied

Scientific EffectSolubilization: Solvation

Implementation Method 2

the formulation ranges in pH from 6.5 to 8.5

Methodology Applied

Scientific EffectpH adjustment:

Implementation Method 3

an injection container with reduced oxygen levels through nitrogen substitution to ensure stability and safety

Methodology Applied

Scientific EffectNitrogen substitution:

Data Source

PatentUS20240033215A1Injectable formulation with enhanced stability containing dexibuprofen and arginin and their medicine vessel for injection

Publication Date: 2024.02.01 AMOS PHARM

AI summary

Disclosed herein are an injectable formulation with improved stability and an injectable formulation with improved storage stability. The injectable formulation with improved stability comprises dexibuprofen and arginine and ranging in pH from 6.5 to 8.5, wherein arginine is contained in an amount of 300 to 500 parts by weight and preferably in an amount of 320 to 330 parts by weight, based on 400 parts by weight of dexibuprofen, and the injectable formulation with improved storage stability is prepared by subjecting the injectable formulation with improved stability to nitrogen substitution and loading the nitrogen-substituted formulation into a storage container, with a saturation oxygen of 5% or less therein.