Levofloxacin-Ketorolac Eye Drop Composition for Precipitation Stability
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Solution Overview
Problem
Current ophthalmic compositions combining antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) face stability issues due to incompatibility and chemical reactions between active ingredients, leading to undesired by-products and reduced effectiveness.
Innovation Solution
A stable ophthalmic composition is formulated with levofloxacin and ketorolac tromethamine at specific concentration ranges (0.4 to 0.9% w/v) and pH values (7.7 to 8.5), with controlled addition sequences and intermediate pH adjustments during manufacturing to prevent precipitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If levofloxacin and ketorolac are combined in an ophthalmic composition, then the therapeutic efficacy for treating infectious and inflammatory states is improved, but the storage stability deteriorates due to incompatibility and chemical reactions between active ingredients
Solution Approach 1:
The patent applies parameter changes by carefully controlling the pH of the ophthalmic composition within a specific range (pH 6.0-7.5) to prevent chemical reactions between levofloxacin and ketorolac. This pH control resolves the contradiction by maintaining stability conditions that allow both drugs to coexist without degradation, while preserving their therapeutic efficacy for treating infectious and inflammatory eye conditions.
2Reliability
If the concentration of active ingredients is increased to enhance therapeutic effect, then the treatment effectiveness is improved, but the precipitation risk increases reducing formulation stability
Solution Approach 1:
The patent utilizes parameter changes by optimizing the concentration ranges of levofloxacin (0.1-5% w/v) and ketorolac (0.1-5% w/v) within the pH 6.0-7.5 range. This simultaneous optimization of concentration and pH parameters allows the formulation to achieve effective therapeutic doses while preventing precipitation, thus resolving the contradiction between treatment effectiveness and formulation stability.
3Stability of the object's composition
If separate administration of antibiotic and anti-inflammatory drugs is used, then the compatibility and stability are maintained, but the treatment complexity and patient compliance worsen
Solution Approach 1:
The patent applies the merging principle by formulating levofloxacin and ketorolac together in a single ophthalmic composition. By resolving their compatibility issues through pH control (pH 6.0-7.5), the patent enables combination therapy in one formulation, reducing treatment complexity and improving patient compliance while maintaining drug compatibility and stability.
Solution Approach 2:
The patent achieves universality by creating a multi-functional ophthalmic composition that simultaneously provides antibiotic activity (levofloxacin) and anti-inflammatory activity (ketorolac). This single formulation addresses multiple therapeutic needs, eliminating the requirement for separate drug administrations and simplifying the treatment regimen while maintaining stability through controlled pH conditions.
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 ensures long-term stability and compatibility of levofloxacin and ketorolac, maintaining therapeutic efficacy and patient compliance by preventing precipitate formation.
Implementation Method 1
wherein said composition has a pH value ranging from 7.7 to 8.5
Implementation Method 2
Levofloxacin has a molecular weight of 361.4 g/mol and is poorly soluble in water, but sufficiently lipophilic to penetrate the eyes
Implementation Method 3
Its solubility profile shows a pH dependent trend, significantly increasing at pH value > 6.0
Data Source
AI summary
The present invention relates to a storage-stable pharmaceutical composition for ophthalmic administration in the form of an aqueous solution comprising a therapeutically effective amount of antibiotic levofloxacin or a pharmaceutically acceptable salt or derivative thereof, as a first active ingredient, and a therapeutically effective amount of non-steroidal anti-inflammatory and analgesic ketorolac or a pharmaceutically acceptable salt or derivative thereof, as a second active ingredient, wherein said first active ingredient is from about 0.4 to about 0.9% w/v and said second active ingredient is from about 0.4 to about 0.9% w/v, wherein the weight/volume percentages are expressed as g/100mL units, in order to prevent the precipitation and improve the stability of the product.