Low-Sorbing Glyburide Formulation for Stable IV Dosing
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Solution Overview
Problem
Glyburide formulations suffer from instability, sorption to delivery containers, and low solubility in typical pH ranges for infusion solutions, leading to sub-therapeutic doses and increased saline use, which is critical in emergency care settings.
Innovation Solution
Formulations comprising glyburide, a buffering agent, and a sugar alcohol with a pH outside the buffering agent's capacity, minimizing sorption and maintaining stability and solubility, allowing precise dosing with commonly used medical supplies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If glyburide is formulated in buffered aqueous solutions at typical pH ranges (pH 5-9), then the formulation is compatible with infusion solutions, but the glyburide concentration is reduced due to sorption to delivery containers and degradation
Solution Approach 1:
The patent changes the pH parameter from the typical infusion range (pH 5-9) to a higher range (pH 10-12). This parameter change resolves the contradiction by reducing sorption to delivery containers and degradation while maintaining compatibility with infusion solutions through proper buffering agent selection and concentration control.
2Ease of operation
If glyburide is dissolved in buffered aqueous solutions, then the formulation can be administered intravenously, but the solubility is extremely low requiring large volumes of saline
Solution Approach 1:
The patent changes the pH parameter to a higher range (pH 10-12) which dramatically increases glyburide solubility. This allows the same therapeutic dose to be delivered in smaller volumes of infusion solution, resolving the contradiction between administrability and saline volume requirements.
3Reliability
If specialized low-sorbing infusion sets are used to reduce glyburide sorption, then the glyburide concentration is maintained, but the device complexity and difficulty of sourcing increase
Solution Approach 1:
The patent converts the harmful effect of sorption into a beneficial formulation characteristic by adjusting the pH to 10-12. This causes glyburide to exist in a deprotonated state that has minimal affinity for common infusion set materials, eliminating the need for specialized equipment while maintaining concentration stability.
Solution Approach 2:
The patent changes the pH parameter to resolve the contradiction between concentration maintenance and device complexity. By formulating at pH 10-12, the glyburide becomes compatible with standard infusion sets, eliminating the need for specialized low-sorbing equipment.
4Quantity of substance
If the pH is adjusted to increase glyburide solubility, then the solubility improves, but the formulation becomes less stable due to degradation
Solution Approach 1:
The patent changes the pH parameter to a specific higher range (pH 10-12) and combines this with specific buffering agent selections. This resolves the contradiction by finding the optimal pH window where solubility is maximized while degradation is minimized through proper buffer system selection.
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
Stable glyburide formulations with reduced sorption and degradation, enabling accurate dosing and minimizing saline use, suitable for emergency treatments.
Implementation Method 1
a buffering agent; a base; and a sugar alcohol, wherein the formulation has a pH outside of the buffering capacity of the buffering agent
Implementation Method 2
a buffering agent, a base, and a sugar alcohol, wherein the formulation has a pH outside of the buffering capacity of the buffering agent
Data Source
AI summary
Methods and formulations for minimizing or avoiding the sorption of glyburide to surfaces of delivery tubing, filters, bags, and other containers and materials, thereby storing and delivering a more stable product, delivering a predictable and accurate dose of glyburide, while minimizing impurities, avoiding drug waste, reducing cost, and significantly reducing the amount of dosing solution that must be infused into the patient.