Clear Aqueous Ophthalmic Solution Turbidity Control
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Solution Overview
Problem
Benzalkonium chloride, commonly used as a preservative in aqueous liquid preparations, interacts with compounds having anionic groups, leading to salt formation and white turbidity issues in ophthalmic solutions and other aqueous preparations containing (3-{2-[4-isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]ethyl}-5-methyl-1,2-benzisoxazol-6-yl)oxyacetic acid, affecting their clarity and stability.
Innovation Solution
Adding a specific concentration of benzalkonium chloride with varying alkyl chain lengths, either as a single component or a mixture, to the aqueous liquid preparations to maintain clarity and preservation stability, ensuring a transmittance of at least 98% at 600 nm and optimizing the concentration range to prevent white turbidity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If benzalkonium chloride is added as a preservative to aqueous liquid preparations containing compound A, then preservation stability is improved, but white turbidity occurs due to salt formation between the cationic preservative and anionic compound
Solution Approach 1:
The patent applies parameter changes by carefully controlling the concentration of benzalkonium chloride within specific ranges (0.001-0.1% w/v) to prevent salt formation and white turbidity while maintaining preservation stability. This quantitative parameter optimization resolves the contradiction between effective preservation and visual clarity.
Solution Approach 2:
The patent uses composite preservative systems combining benzalkonium chloride with other preservatives or stabilizers in specific ratios. This composite approach allows the formulation to achieve both preservation stability and clarity by distributing the preservative function across multiple components, reducing the concentration of any single cationic preservative that could cause salt formation.
2Reliability
If higher concentration of benzalkonium chloride is used to ensure preservation stability, then preservation effectiveness is improved, but interaction with compound A increases leading to more severe white turbidity
Solution Approach 1:
The patent establishes specific concentration thresholds for benzalkonium chloride (0.001-0.1% w/v) that optimize preservation effectiveness while preventing excessive interaction with compound A. This parameter control ensures the preservative concentration is sufficient for stability but low enough to avoid visible salt formation.
Solution Approach 2:
The patent introduces intermediary substances such as surfactants or chelating agents that mediate between the cationic benzalkonium chloride and anionic compound A. These intermediaries prevent direct salt formation while allowing the preservative to maintain its antimicrobial effectiveness.
Data Source
AI summary
The present invention provides a stable and clear aqueous liquid preparation containing (3-{2-[4-isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]ethyl}-5-methyl-1,2-benzisoxazol-6-yl)oxyacetic acid or a pharmaceutically acceptable salt thereof as an active ingredient, and benzalkonium chloride represented by the formula: [C6H5CH2N(CH3)2R]Cl wherein R is an alkyl group having 8 - 18 carbon atoms.