Bromfenac Ophthalmic Composition Preservative Efficacy
Solution Overview
Problem
Aqueous liquid bromfenac compositions with benzalkonium chloride lack sufficient preservative efficacy, leading to potential side effects and instability, particularly when used in ophthalmic solutions.
Innovation Solution
Combining bromfenac sodium with an aqueous base containing a low concentration of benzalkonium chloride, where the concentration of benzalkonium chloride is between 0.0005% and 0.005%, enhances preservative efficacy and stability, even when used in low amounts, effectively reducing bacterial proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If benzalkonium chloride is added to ophthalmic solutions at conventional concentrations (0.002%-0.005%), then preservative efficacy is achieved, but side effects and corneal damage occur
Solution Approach 1:
The patent changes the concentration parameter of benzalkonium chloride from conventional levels (0.002%-0.005%) to a lower range (0.0005%-0.002%), and introduces bromfenac as a synergistic component to maintain preservative efficacy at this reduced concentration, thereby resolving the contradiction between efficacy and safety
Solution Approach 2:
The patent creates a composite preservative system combining benzalkonium chloride with bromfenac, where the two substances work synergistically to provide effective preservation at lower benzalkonium chloride concentrations, reducing harmful effects while maintaining reliability
2Object-affected harmful factors
If benzalkonium chloride is added at low concentrations (0.001%-0.005%), then safety is improved, but preservative efficacy becomes insufficient
Solution Approach 1:
The patent combines benzalkonium chloride with bromfenac to create a synergistic preservative system that maintains effective preservation activity at low benzalkonium chloride concentrations (0.0005%-0.002%), thereby achieving both safety improvement and efficacy maintenance
Solution Approach 2:
The patent adjusts the concentration parameters of both benzalkonium chloride and bromfenac to optimal levels where the synergistic effect is maximized, allowing sufficient preservative efficacy to be achieved at reduced benzalkonium chloride concentrations that improve safety
3Stability of the object's composition
If non-ionic surfactants are added to aqueous liquids, then formulation stability is improved, but preservative efficacy of benzalkonium chloride deteriorates
Solution Approach 1:
The patent optimizes the concentration parameter of non-ionic surfactants to levels that do not interfere with benzalkonium chloride's preservative action, while maintaining formulation stability through other means, thereby resolving the contradiction between stability and efficacy
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 resulting aqueous liquid bromfenac composition demonstrates improved preservative efficacy, meeting microbiological testing standards, such as those specified in the Japanese Pharmacopoeia and USP, while minimizing side effects and ensuring stability over time.
Implementation Method 1
benzalkonium chloride forms complexes with other substances in an aqueous liquid, resulting in impaired preservative efficacy. In particular, it is reported that a combination of a non-steroidal anti-inflammatory drug (NSAID) and a quaternary ammonium salt such as benzalkonium chloride forms a complex
Data Source
AI summary
An aqueous liquid bromfenac composition containing (a) bromfenac or a salt thereof and (b) benzalkonium chloride, characterized by that the composition has preservative efficacy and that the concentration of (b) benzalkonium chloride is higher than 0.0005% and lower than 0.005%.