ReST Glucagon Solid Formulation for Painless Microneedle Delivery
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Solution Overview
Problem
Current glucagon treatments for hypoglycemia, especially for mild and non-emergent cases, are limited by the insoluble and unstable nature of glucagon, leading to pain, complexity, and suboptimal use.
Innovation Solution
Development of high-density, readily soluble, and thermostable (ReST) solid glucagon formulations, combined with innovative delivery systems such as microneedle patches and glucose-responsive wearable patches, to enable accurate, painless, and convenient glucagon administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If glucagon is formulated as a solution for rapid administration, then the treatment speed is improved, but the formulation becomes unstable and forms insoluble fibrils during storage
Solution Approach 1:
The patent changes the physical state parameter of glucagon from solution to solid powder form. This parameter change allows the glucagon to be stored stably in dry form and only converted to solution state at the moment of administration, thus resolving the contradiction between storage stability and treatment speed. The solid-to-solution transition is achieved through reconstitution with water or saline immediately before use.
2Reliability
If glucagon is administered via needle injection for rapid effect, then the treatment efficacy is improved, but the patient experiences pain and fear
Solution Approach 1:
The patent segments the administration process into two distinct stages: (1) painless transdermal delivery of the solid glucagon powder through microneedles or patch, and (2) subsequent dissolution and absorption in the skin. This segmentation allows the beneficial rapid delivery to be achieved while eliminating the harmful needle injection pain by using multiple smaller, less invasive entry points.
Solution Approach 2:
The patent introduces the skin and interstitial fluid as an intermediary medium between the glucagon powder and the bloodstream. Instead of direct intravenous or intramuscular injection, the glucagon is delivered through the skin barrier and releases into the interstitial fluid, which then mediates the transport to systemic circulation. This intermediary approach maintains treatment efficacy while eliminating injection pain.
3Measurement precision
If glucagon is delivered in high concentration for efficient dosing, then the dosing accuracy is improved, but the formulation density limits loading in ingestible or transdermal devices
Solution Approach 1:
The patent changes the concentration parameter by using highly concentrated solid glucagon powder formulations with up to 80-90% glucagon content. This high solid-state concentration overcomes the density limitation of liquid formulations, enabling sufficient drug loading in small transdermal or ingestible devices while maintaining dosing accuracy through precise powder dosing mechanisms.
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 ReST glucagon formulations and delivery systems provide a stable, efficient, and user-friendly means to manage hypoglycemia, expanding the clinical role of glucagon beyond emergency settings and improving glycemic management for people with diabetes.
Implementation Method 1
a pH-responsive polymer. The polymeric release structure swells and/or dissolves at a pH level of about 6 or greater and the glucagon is released from the polymeric release structure when the mammalian subject has a glucose concentration of about 100 milligrams per deciliter or less (which corresponds to a pH level of about 6 or greater)
Implementation Method 2
at least one of glucose oxidase, a glucose oxidase derivative, or a glucose oxidase analogue
Implementation Method 3
at least one of glucose oxidase, a glucose oxidase derivative, or a glucose oxidase analogue
Data Source
AI summary
Insulin therapy revolutionized the care of patients with diabetes, yet insulin-induced hypoglycemia remains a serious life-threatening complication of insulin therapy. Glucagon is a highly effective treatment for hypoglycemia; however, current dosage forms remain under-utilized due to poor patient compliance. High-density, readily soluble, and thermostable solid glucagon formulations applied with painless, application-specific microneedle-patches can treat hypoglycemia in type 1 diabetes patients who are awake or asleep. On-demand patches can prevent or treat mild hypoglycemia during the day, and enzyme-driven hypoglycemia-responsive patches can release glucagon autonomously during the night. These patches have excellent in vitro glucagon stability, loading, and release kinetics and can treat hypoglycemia in diabetic humans and animals. These delivery systems enable new modes of glucagon therapy, thereby expanding the clinical role of glucagon beyond the emergency setting.