Arginine–Ibuprofen Injectable Composition for Buffer-Free pH Stability

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Solution Overview

Problem

Existing injectable ibuprofen formulations face issues with stability, require buffers and osmotic agents like sodium and dextrose, which can lead to increased blood pressure, cardiovascular risks, and local tissue damage, while maintaining pH stability is crucial for safety.

Innovation Solution

A composition comprising ibuprofen and arginine in a specific molar ratio, combined with mannitol as a diuretic, forms a stable, sodium-free, dextrose-free, and buffer-free solution, maintaining pH close to physiological levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If ibuprofen is combined with arginine and sodium chloride or dextrose to create an injectable formulation, then solubility is improved, but cardiovascular risks and blood pressure increase

Engineering Contradiction:
ImprovesolubilityVSAvoidcardiovascular risks
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent removes sodium chloride and dextrose from the formulation, extracting the harmful osmotic agents while retaining arginine as the sole solubilizing agent. This eliminates the cardiovascular risks associated with sodium and dextrose while maintaining ibuprofen solubility through the arginine complex.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical composition parameters by eliminating sodium chloride and dextrose, and instead using a specific molar ratio of arginine (1:0.92 to 1:1.05) to solubilize ibuprofen. This parameter change achieves both solubility and safety requirements.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If buffers are used to stabilize pH in ibuprofen formulations, then pH stability is improved, but blood coagulation time increases and tissue damage risk increases

Engineering Contradiction:
ImprovepH stabilityVSAvoidtissue damage
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent removes traditional buffer systems (such as trometamol, sodium phosphate, or potassium phosphate) from the formulation. Instead, it relies on the arginine-ibuprofen complex itself to maintain pH within the safe range of 7.4 to 8.5, eliminating the risk of tissue damage associated with conventional buffers.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The arginine-ibuprofen complex serves a dual function: it solubilizes the ibuprofen and simultaneously acts as a self-regulating pH system. The complex maintains pH within the safe range without requiring additional buffer agents, making the formulation self-sufficient and safe.

Inventive Principle:
Principle #25Self-service

3Reliability

If sodium chloride is used as an osmotic agent in ibuprofen formulations, then isotonicity is improved, but blood pressure and cardiovascular risks increase

Engineering Contradiction:
ImproveisotonicityVSAvoidblood pressure
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces sodium chloride with arginine as the osmotic agent. The arginine-ibuprofen complex provides the necessary isotonicity without introducing sodium into the bloodstream, thereby eliminating the blood pressure and cardiovascular risks associated with sodium chloride-based formulations.

Inventive Principle:
Principle #2Taking out (Extraction)

4Use of energy by moving object

If dextrose is used in ibuprofen formulations, then energy supply is improved, but cardiovascular risks and blood pressure increase

Engineering Contradiction:
Improveenergy supplyVSAvoidcardiovascular risks
Core Design Contradiction:
Use of energy by moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent removes dextrose from the formulation entirely. The arginine-ibuprofen complex provides sufficient stability and isotonicity without requiring dextrose, thereby eliminating the cardiovascular risks and blood pressure increases associated with dextrose-containing formulations.

Inventive Principle:
Principle #2Taking out (Extraction)

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 solution provides a stable ibuprofen formulation that reduces risks associated with cardiovascular disorders, hypertension, and local tissue damage, ensuring patient safety and clinical efficacy by avoiding buffers and osmotic agents, with improved stability and reduced hospitalization time.

Implementation Method 1

in combination with a aqueous solution of a diuretic compound comprising between 4.05% and 4.25 % w/v of the diuretic compound, which is mannitol

Methodology Applied
Scientific EffectDiuresis:

Implementation Method 2

Different combinations of Ibuprofen with amino acids were developed to solubilize Ibuprofen in water. The existing claimed formulations available for Ibuprofen injectable contain combination of Ibuprofen with Arginine

Methodology Applied
Scientific EffectSolubilization: Solvation

Data Source

PatentEP3493788B1Stable ibuprofen injectable composition
Publication Date: 2025.10.29 AMBAH IP LTD

AI summary

The present invention relates to a composition for injectable formulation, the composition comprising:- An aqueous solution of ibuprofen and arginine with a molar ratio of ibuprofen:arginine comprised between 1:1.1 and 1:2.1;- An aqueous solution of a diuretic compound comprising between 3.9 % and 4.35 % w/v of the diuretic compound.The present invention also concerns a pharmaceutical composition comprising said composition and the use of said composition and said pharmaceutical composition.