Brimonidine Ophthalmic Composition With SBE-β-CD for Stable Clear Solutions
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Brimonidine, an alpha-2-adrenergic agonist used for treating glaucoma and ocular hypertension, has low solubility at biocompatible pH levels above 7, making it difficult to formulate into a stable, transparent ophthalmic solution with high concentrations.
Innovation Solution
An ophthalmic composition comprising brimonidine or its salts, sulfobutylether-β-cyclodextrin (SBE-β-CD) or its salts, and xanthan gum, which stabilizes brimonidine dissolution and maintains a transparent, stable solution during storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If the pH of the ophthalmic composition is increased above 7 to improve biocompatibility and reduce irritation, then the therapeutic effect and convenience of taking the medication is improved, but the solubility of brimonidine rapidly decreases making it difficult to formulate into a transparent aqueous solution
Solution Approach 1:
The patent introduces sulfobutylether-β-cyclodextrin (SBE-β-CD) as an intermediary substance that forms inclusion complexes with brimonidine. This mediator enables brimonidine to remain soluble in aqueous solutions at physiological pH levels by incorporating it into its molecular structure, thus resolving the contradiction between maintaining biocompatibility and ensuring drug solubility
Solution Approach 2:
The patent changes the chemical state of brimonidine by converting it into a salt form (brimonidine tartrate) and using it in combination with specific excipients. This parameter change allows the drug to maintain solubility at pH levels above 7, enabling formulation of transparent aqueous solutions while preserving biocompatibility
2Reliability
If the content of brimonidine in the ophthalmic preparation is increased to secure further increased therapeutic effect, then the treatment efficacy is improved, but the solubility problem worsens making it difficult to maintain biocompatibility
Solution Approach 1:
SBE-β-CD acts as a mediator that can accommodate higher concentrations of brimonidine in its inclusion complex structure. This allows the formulation to achieve increased therapeutic efficacy through higher drug content while maintaining biocompatibility, as the mediator prevents precipitation and maintains solution stability even at elevated concentrations
Solution Approach 2:
The patent creates a composite formulation combining brimonidine tartrate, SBE-β-CD, and xanthan gum. This composite material system enables the simultaneous achievement of high drug content and maintained biocompatibility, as the combination provides both solubility enhancement and physiological compatibility
3Object-affected harmful factors
If brimonidine is formulated into an aqueous solution at biocompatible pH levels, then the medication is safe for eyeballs, but the solution becomes unstable occurring precipitation and discoloration during storage
Solution Approach 1:
SBE-β-CD serves as a protective intermediary that forms stable inclusion complexes with brimonidine, preventing the drug from precipitating or degrading during storage. This mediator maintains both the biocompatibility and storage stability of the aqueous solution, resolving the contradiction between safety and stability
Solution Approach 2:
The composite formulation of brimonidine tartrate, SBE-β-CD, and xanthan gum creates a synergistic system that enhances both biocompatibility and storage stability. The combination prevents precipitation and maintains solution clarity over time while remaining safe for ocular use
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 stable brimonidine solubility and transparency, preventing precipitation and maintaining physicochemical stability for extended periods, enabling safe and effective administration for glaucoma and ocular hypertension treatment.
Implementation Method 1
sulfobutylether-β-cyclodextrin (SBE-β-CD) or salts thereof... which stabilizes brimonidine dissolution and maintains a transparent, stable solution during storage
Implementation Method 2
xanthan gum, which stabilizes brimonidine dissolution and maintains a transparent, stable solution during storage
Data Source
Figure 1~2
AI summary
The present invention relates to an ophthalmic composition including brimonidine or salts thereof, SBE-β-CD or salts thereof, and xanthan gum, thereby showing excellent safety, stability and therapeutic effects.