D2O Ophthalmic Formulations to Reduce Base-Catalyzed Hydrolysis
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Solution Overview
Problem
Pharmaceutical formulations, particularly ophthalmic compositions, face stability issues due to degradation of active ingredients through base-catalyzed hydrolysis, leading to reduced efficacy and poor eye tolerance.
Innovation Solution
Formulating ophthalmic compositions with deuterated water (D2O) at a pD of 4 to 8, which stabilizes the active agents by reducing base-catalyzed hydrolysis and minimizes tear reflex, thereby maintaining high agent concentration and eye tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional water (H2O) is used in ophthalmic formulations, then the formulation can be prepared with standard pH control, but base-catalyzed hydrolysis degrades the active ingredient leading to reduced stability and efficacy
Solution Approach 1:
The patent replaces conventional water (H2O) with deuterated water (D2O) in the ophthalmic formulation. This parameter change in the solvent composition fundamentally alters the chemical environment, reducing base-catalyzed hydrolysis rates and thereby improving the stability of the active ingredient while maintaining its therapeutic efficacy.
Solution Approach 2:
The formulation uses a composite solvent system comprising deuterated water (D2O) combined with conventional water (H2O) in specific ratios. This composite approach allows optimization of stability properties while maintaining biocompatibility and appropriate pharmacological activity of the active ingredient.
2Stability of the object's composition
If pH is reduced to prevent base-catalyzed hydrolysis, then stability improves, but eye tolerance deteriorates due to irritation and tear reflex
Solution Approach 1:
Instead of adjusting pH to improve stability, the patent changes the solvent isotope composition from H2O to D2O. This parameter change provides stability enhancement without the need for pH reduction, thereby avoiding ocular irritation and maintaining good eye tolerance.
3Quantity of substance
If deuterated water (D2O) is used to stabilize active agents, then agent retention increases, but formulation complexity increases
Solution Approach 1:
The patent employs a straightforward parameter change by substituting D2O for H2O in the formulation. This simple replacement achieves enhanced agent retention without requiring complex formulation strategies, manufacturing processes, or storage conditions, thereby minimizing formulation complexity.
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 use of deuterated water in ophthalmic compositions ensures high agent retention (up to 99%) over extended periods, enhances stability, and improves eye tolerance by reducing tear dilution and irritation.
Implementation Method 1
Pharmaceutical formulations, particularly ophthalmic compositions, face stability issues due to degradation of active ingredients through base-catalyzed hydrolysis
Implementation Method 2
minimizes tear reflex, thereby maintaining high agent concentration and eye tolerance
Data Source
AI summary
Provided herein is an ophthalmic composition formulated in deuterated water. Also disclosed herein are methods of treating, ameliorating, or reducing ophthalmic conditions or diseases by administering to an eye of an individual in need thereof an effective amount of an ophthalmic composition as described herein.