Artificial Vitreous Humor Composition for Stable Drug Release Testing
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Solution Overview
Problem
Existing in-vitro tests for drug stability in vitreous humor (VH) fail to accurately simulate real in vivo conditions due to rapid pH changes and degradation, and natural VH from animal sources exhibit significant biological variabilities, making it difficult to predict drug stability and release behavior.
Innovation Solution
Development of an artificial vitreous humor (aVH) composition comprising a phosphate buffer with a pH of 7.4 and specific small and large molecular weight components, such as creatinine, glucose, urea, xanthine, hypoxanthine, sodium lactate, glutathione, collagen, and hyaluronate, which mimics human VH to provide controlled physical and chemical parameters for stability and release prediction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If natural vitreous humor from animal sources is used for in-vitro tests, then the test system is simple to prepare, but significant biological variabilities in viscosity and density make stability predictions unreliable
Solution Approach 1:
The patent creates an artificial copy of natural vitreous humor by synthesizing aVH with controlled composition (collagen 0.1-1.0 mg/mL, hyaluronic acid 0.01-0.1 mg/mL, and physiological salts) that replicates the physical and chemical properties of natural VH without using actual animal-derived materials. This copying approach eliminates biological variability while maintaining physiological relevance for drug stability testing.
Solution Approach 2:
The patent precisely controls and standardizes key parameters of the artificial vitreous humor including viscosity (0.5-2.0 cP), density (1.00-1.01 g/mL), pH (7.0-7.5), and component concentrations. By fixing these parameters within specific ranges, the invention eliminates the variability inherent in natural animal-derived VH while maintaining physiological conditions necessary for accurate drug stability prediction.
2Device complexity
If vitreous humor is used outside its natural environment for testing, then the test setup is simplified, but the pH value increases rapidly due to accumulation of degradation products, making tests unrepresentative of in vivo conditions
Solution Approach 1:
The patent creates an artificial copy of natural vitreous humor by synthesizing aVH with controlled composition (collagen 0.1-1.0 mg/mL, hyaluronic acid 0.01-0.1 mg/mL, and physiological salts) that replicates the physical and chemical properties of natural VH without using actual animal-derived materials. This copying approach eliminates biological variability while maintaining physiological relevance for drug stability testing.
Solution Approach 2:
The patent employs a disposable semi-permeable membrane (molecular weight cutoff 10-50 kDa) that allows degradation products to be removed from the test system after use. This single-use approach prevents pH drift during testing while eliminating the need for complex reusable stabilization systems, maintaining both simplicity and pH stability.
3Stability of the object's composition
If a buffering system is applied to stabilize pH in vitreous humor tests, then pH stability is improved, but degradation products must leave through a semi-permeable membrane adding system complexity
Solution Approach 1:
The patent creates an artificial copy of natural vitreous humor by synthesizing aVH with controlled composition (collagen 0.1-1.0 mg/mL, hyaluronic acid 0.01-0.1 mg/mL, and physiological salts) that replicates the physical and chemical properties of natural VH without using actual animal-derived materials. This copying approach eliminates biological variability while maintaining physiological relevance for drug stability testing.
Solution Approach 2:
The patent employs a disposable semi-permeable membrane (molecular weight cutoff 10-50 kDa) that allows degradation products to be removed from the test system after use. This single-use approach prevents pH drift during testing while eliminating the need for complex reusable stabilization systems, maintaining both simplicity and pH stability.
4Reliability
If intravitreal injection is used to deliver drugs, then bioavailability to the retina is high, but the drug remains in the vitreous humor for significantly longer duration requiring stable physiological conditions for accurate stability study
Solution Approach 1:
The patent creates an artificial copy of natural vitreous humor by synthesizing aVH with controlled composition (collagen 0.1-1.0 mg/mL, hyaluronic acid 0.01-0.1 mg/mL, and physiological salts) that replicates the physical and chemical properties of natural VH without using actual animal-derived materials. This copying approach eliminates biological variability while maintaining physiological relevance for drug stability testing.
Solution Approach 2:
The patent precisely controls and standardizes key parameters of the artificial vitreous humor including viscosity (0.5-2.0 cP), density (1.00-1.01 g/mL), pH (7.0-7.5), and component concentrations. By fixing these parameters within specific ranges, the invention eliminates the variability inherent in natural animal-derived VH while maintaining physiological conditions necessary for accurate drug stability prediction over extended periods.
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 aVH composition serves as a reliable in-vitro model for predicting drug stability and release behavior, offering improved robustness and accuracy in simulating physiological conditions for up to 360 days, allowing for realistic test results on drug formulations and DDS systems.
Implementation Method 1
The phosphate buffer has a pH value in the range from 7.0 to 7.7, particularly from 7.1 to 7.6, more particularly from 7.2 to 7.5. Most particularly the phophate buffer has a pH value of 7.4.
Implementation Method 2
We have evaluated novel compositions of aVH comprising a buffer system, small molecular weight (SMW) components and large molecular weight (LMW) components such as matrix forming polymers, which can then serve as an in-vitro model for the prediction of drug or drug formulation stability
Data Source
AI summary
The invention relates to an artificial vitreous humor composition comprising a phosphate buffer, wherein the phosphate buffer has a pH value in the range from 7.0 to 7.7, particularly from 7.1 to 7.6, more particularly from 7.2 to 7.5. The invention further relates to a method of production of an artificial vitreous humor composition, a method for analyzing the behavior of a substance, a method for analyzing the change of the artificial vitreous humor composition upon contact with a substance and a kit of parts.