Glyburide Infusion Formulation for Low Sorption and Stable 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 drug waste, particularly in emergency care settings where time is critical.
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 for precise dosing and reduced infusion volume.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If glyburide is formulated in buffered aqueous solutions at typical pH ranges (pH 5-9), then the formulation is suitable for infusion, but the solubility of glyburide is extremely low and it is practically insoluble
Solution Approach 1:
The patent raises the pH of the formulation to above 9.0 (specifically pH 9.5-11.0), which is outside the typical buffered aqueous solution range. This parameter change dramatically increases glyburide solubility from extremely low levels to sufficient concentrations for therapeutic infusion while maintaining physiological compatibility
2Ease of operation
If glyburide is stored in conventional pharmaceutical containers and delivery systems, then the formulation can be administered, but significant amounts of glyburide are lost due to sorption to container surfaces and delivery tubing
Solution Approach 1:
The elevated pH formulation (pH 9.5-11.0) fundamentally alters the chemical properties of glyburide, reducing its affinity for sorption to conventional container and delivery system surfaces. This parameter change enables the use of standard pharmaceutical containers and tubing without significant drug loss, eliminating the need for specialized low-sorbing components
3Manufacturing precision
If glyburide formulations are diluted for infusion, then the drug can be administered at therapeutic concentrations, but the diluted solution readily binds to plastics in infusion components causing sub-therapeutic dosing
Solution Approach 1:
The patent maintains the high pH (9.5-11.0) through the dilution process, which prevents glyburide from binding to plastic surfaces in infusion bags and tubing. This ensures that the diluted infusion solution delivers the intended therapeutic dose accurately without sub-therapeutic loss to container surfaces
4Loss of substance
If specialized low-sorbing infusion sets are used to prevent glyburide sorption, then drug loss is reduced, but the complexity of the administration system increases and sourcing becomes difficult
Solution Approach 1:
By formulating glyburide at pH 9.5-11.0, the patent eliminates the need for specialized low-sorbing infusion sets. The high pH formulation is compatible with conventional plastic infusion components, significantly simplifying the administration system and making sourcing straightforward while still preventing significant drug loss
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
Stabilizes glyburide formulations, ensuring accurate dosing with minimal loss and waste, even in commonly used medical supplies, and maintaining pH stability during infusion.
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.