Buffer-Free Ketorolac and Phenylephrine Ophthalmic Composition
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Solution Overview
Problem
Current ophthalmological formulations often require buffering agents to maintain ocular pH, which can be complex and lead to instability and adverse effects, especially when combining active pharmaceutical ingredients like ketorolac and phenylephrine, necessitating the development of buffer-free compositions that maintain stability and efficacy.
Innovation Solution
The development of ophthalmological compositions comprising pharmaceutically acceptable amounts of ketorolac and phenylephrine compounds without a buffer component, maintaining a pH between 5.5 and 7, and retaining stability and effectiveness for extended periods without significant pH changes, even under varying storage conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If buffer components are used to maintain ocular pH, then pH stability is improved, but formulation complexity and risk of adverse effects increase
Solution Approach 1:
The patent removes buffer components from the formulation entirely, extracting the problematic element that caused complexity while maintaining pH stability through alternative means (ketorolac tromethamine salt selection and pH adjustment to 6.3-6.7). This eliminates the need for additional buffering agents and simplifies the formulation.
Solution Approach 2:
The ketorolac tromethamine salt itself provides pH stabilization through its inherent buffer capacity in the physiological range, allowing the formulation to self-regulate pH without requiring external buffer additives. The salt's conjugate acid-base pairs naturally maintain pH within the desired range.
2Stability of the object's composition
If buffer components are used to maintain ocular pH, then pH stability is improved, but the risk of adverse effects increases
Solution Approach 1:
By removing traditional buffer components (phosphate, citrate, acetate buffers) from the formulation, the patent eliminates the source of potential adverse effects while maintaining pH stability through the ketorolac tromethamine salt's inherent buffering properties and pH adjustment to 6.3-6.7.
Solution Approach 2:
The patent uses a single, well-chosen salt (ketorolac tromethamine) that provides sufficient buffering capacity for the entire shelf life of the formulation, eliminating the need for complex multi-component buffer systems that could cause adverse effects.
3Device complexity
If buffer-free compositions are used, then formulation simplicity is improved, but maintaining stability over time becomes more difficult
Solution Approach 1:
The patent optimizes the pH parameter to 6.3-6.7 and selects ketorolac tromethamine salt with specific buffering characteristics to maintain stability over time without requiring external buffers. This parameter optimization allows the formulation to remain stable throughout its shelf life while maintaining simplicity.
Solution Approach 2:
The ketorolac tromethamine salt provides self-regulating pH stability through its conjugate acid-base pairs, automatically maintaining pH within the 6.3-6.7 range without requiring external buffer components. This self-service mechanism ensures long-term stability while keeping the formulation simple.
4Object-affected harmful factors
If buffer-free compositions are used, then adverse effects are reduced, but achieving stable pH becomes more difficult
Solution Approach 1:
The ketorolac tromethamine salt provides self-regulating pH stability through its conjugate acid-base pairs, automatically maintaining pH within the 6.3-6.7 range without requiring external buffer components. This self-service mechanism ensures stable pH while avoiding adverse effects from traditional buffers.
Solution Approach 2:
The patent optimizes the pH parameter to 6.3-6.7 and selects ketorolac tromethamine salt with specific buffering characteristics to maintain stability over time without requiring external buffers. This parameter optimization achieves stable pH while avoiding adverse effects.
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 buffer-free compositions ensure the stability and effectiveness of ketorolac and phenylephrine, maintaining therapeutic levels for at least 97% of the active ingredients over several months, reducing the risk of adverse effects and improving the stability and shelf-life of ophthalmological products.
Implementation Method 1
the composition is devoid of any buffer component... maintaining a pH between 5.5 and 7... retaining stability and effectiveness for extended periods without significant pH changes
Data Source
AI summary
This invention provides novel compositions comprising an anti-inflammatory agent and a mydriatic agent suitable for intraocular use, particularly ketorolac or pharmaceutically salts thereof and phenylephrine or pharmaceutically salts thereof, which are free of any buffering agent and yet, surprisingly, maintain stability for significant periods of time (e.g., at least about 3 months). The present invention also relates to a process of preparing such compositions and use thereof, e.g., in combination with intraocular ophthalmologic irrigation solutions.