Cyclodextrin Eye Drop Composition for Stable A-5021 Solubilization
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Solution Overview
Problem
Existing antiviral compounds like A-5021 are poorly soluble in physiologically compatible solutions, leading to unstable formulations and ineffective treatment of ocular herpes infections in animals.
Innovation Solution
A-5021 is solubilized under isotonic and pH-neutral conditions using hydroxypropyl beta-cyclodextrin, with optional thiomersal as a preservative, to create stable eye-drop formulations with concentrations between 0.1-1% w/v, suitable for diagnosing and treating ocular herpetic infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If A-5021 is solubilized to pharmacologically active concentrations ( >1 mg/mL), then the antiviral effectiveness is improved, but the solution stability deteriorates due to precipitation
Solution Approach 1:
The patent introduces cyclodextrin as an intermediary substance that forms inclusion complexes with A-5021. This mediator enables the drug to be solubilized at pharmacologically active concentrations ( >1 mg/mL) while maintaining solution stability and preventing precipitation, thus resolving the contradiction between concentration and stability
Solution Approach 2:
The patent changes the physical-chemical parameters of the formulation by adjusting pH to specific ranges (pH 4-6 or pH 8-10) and using cyclodextrin complexes. These parameter changes enable stable solubilization of A-5021 at high concentrations without precipitation, simultaneously achieving both high drug concentration and solution stability
2Reliability
If A-5021 is solubilized at high concentrations (>1 mg/mL), then the treatment effectiveness is improved, but the formulation becomes unstable and precipitates
Solution Approach 1:
Cyclodextrin serves as a stabilizing intermediary that forms soluble inclusion complexes with A-5021, enabling high concentrations ( >1 mg/mL) to be maintained without precipitation. This ensures both treatment effectiveness and formulation stability
Solution Approach 2:
The patent creates a composite formulation system combining A-5021 with cyclodextrin and complementary substances. This composite approach enables high drug concentration while maintaining stability through the synergistic interaction of multiple components, preventing precipitation and ensuring reliable treatment
3Quantity of substance
If pH extreme values ( <4 or >10) are used to solubilize A-5021, then the drug solubility is improved, but the physiological compatibility deteriorates
Solution Approach 1:
Cyclodextrin acts as a pH-independent intermediary that enables A-5021 solubilization at physiological pH levels (pH 4-6 or pH 8-10). This mediator allows high solubility to be achieved without requiring extreme pH values, thus maintaining physiological compatibility
Solution Approach 2:
The patent changes the solubilization approach by using cyclodextrin complexes instead of extreme pH adjustment. This parameter change enables A-5021 to be solubilized at physiologically compatible pH levels while maintaining high solubility and concentration, eliminating the harm of extreme pH
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 compositions provide stable, physiologically tolerable solutions that effectively treat and diagnose ocular herpes infections in animals, with rapid symptom improvement within a week and potential diagnostic utility.
Implementation Method 1
A-5021 is solubilized under isotonic and pH-neutral conditions using hydroxypropyl beta-cyclodextrin
Data Source
AI summary
The present invention relates to an eye-drop composition comprising 2-amino-9-[[(1S,2R)-1,2-bis(hydroxymethyl)cyclopropyl]methyl]-1,9-dihydro-6H-Purin-6-one, and the use thereof for the diagnosis and treatment of herpetic eye infections in companion animals.