Anionic Ophthalmic Compositions Using Polymeric Preservatives
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Solution Overview
Problem
Multi-dose ophthalmic compositions face challenges in maintaining preservation efficacy while minimizing toxicological effects on the cornea, as existing antimicrobial preservatives can interact undesirably with anionic therapeutic agents, leading to instability and potential microbial contamination.
Innovation Solution
An aqueous ophthalmic composition incorporating a polyol like mannitol, borate, and an osmolality enhancing agent, such as sodium chloride, in balanced concentrations to achieve stability, clarity, and preservation efficacy without the need for high surfactant levels, using a polymeric quaternary ammonium compound as a preservative.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antimicrobial preservatives are used in multi-dose ophthalmic compositions, then preservation efficacy is improved, but toxicological effects on the cornea worsen
Solution Approach 1:
The patent changes the chemical parameters of the preservative system by using polymeric quaternary ammonium compounds with specific molecular weights and charge densities, optimizing the balance between antimicrobial efficacy and corneal toxicity. This involves adjusting preservative concentration, molecular structure, and electrostatic properties to achieve effective preservation while minimizing harmful effects on ocular tissues.
2Reliability
If positively charged antimicrobial preservatives are used to prevent microbial contamination, then preservation efficacy is improved, but interaction with anionic therapeutic agents worsens
Solution Approach 1:
The patent introduces non-ionic surfactants as intermediary substances that mediate between the positively charged polymeric preservatives and anionic therapeutic agents. These surfactants reduce direct electrostatic interactions by forming protective complexes or altering the interface properties, thereby preventing precipitation and maintaining composition stability while preserving antimicrobial activity.
3Reliability
If higher concentrations of antimicrobial agents are used to ensure preservation, then preservation efficacy is improved, but toxicological effects worsen
Solution Approach 1:
The patent employs composite preservative systems combining polymeric quaternary ammonium compounds with specific surfactants and formulation excipients. This composite approach creates synergistic effects where the combined system achieves effective preservation at lower overall concentrations, reducing toxicological burden while maintaining or enhancing antimicrobial protection through complementary mechanisms.
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 composition achieves high preservation efficacy, stability, and compatibility with the eye, satisfying USP and other preservative standards while reducing the risk of microbial contamination and minimizing toxicological effects on ocular tissues.
Implementation Method 1
The means employed may be: (i) a chemical agent that prevents the proliferation of microbes in a composition, which is referred to herein as an 'antimicrobial preservative'
Implementation Method 2
The composition includes osmolality enhancing agent wherein the osmolality enhancing agent raises the osmolality of the overall composition at least 160 mOsm/Kg
Data Source
AI summary
The present invention is directed to the provision of multi-dose, ophthalmic compositions. The compositions possess sufficient antimicrobial activity to satisfy USP preservative efficacy requirements, as well as similar preservative standards (e.g., EP and JP). The compositions include a balance of ingredients that allow for the formation of ophthalmic compositions that include an anionic drug and exhibit desired characteristics such as stability, preservation efficacy, desired pH, desired osmolality, combinations thereof or the like.