Non-Aqueous Epinephrine Formulations for Needle-Free Rapid Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing epinephrine formulations are temperature-sensitive, unstable, and require needle-based administration, posing safety risks and usability issues for treating conditions like anaphylaxis and cancer.
Innovation Solution
Development of stable, non-aqueous liquid formulations of epinephrine and its prodrugs, such as dipivefrin, which can be administered orally via sprays, films, or drops, providing rapid systemic delivery comparable to injectable epinephrine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If injectable epinephrine formulations are used, then rapid systemic delivery and therapeutic efficacy are achieved, but needle-based administration causes safety risks and user anxiety
Solution Approach 1:
The patent replaces the mechanical needle-based injection system with a non-mechanical oral liquid formulation system. The epinephrine is delivered via oral administration (liquid form) that is absorbed through the gastrointestinal tract, eliminating the need for needles and mechanical injection while maintaining rapid systemic delivery through the oral absorption pathway.
Solution Approach 2:
The patent uses the gastrointestinal tract and its absorption mechanisms as an intermediary pathway to deliver epinephrine systemically. Instead of direct intramuscular or subcutaneous injection, the formulation utilizes the oral cavity and digestive system as an intermediate route, with epinephrine being absorbed through the gastrointestinal mucosa into the systemic circulation.
2Ease of operation
If aqueous epinephrine formulations are used, then ease of administration is achieved, but temperature sensitivity and instability occur
Solution Approach 1:
The patent fundamentally changes the physical-chemical parameters of the formulation by switching from an aqueous-based system to a non-aqueous liquid system. This parameter change involves altering the solvent type, pH level, and other formulation characteristics to create a stable liquid epinephrine formulation that maintains stability across a wide temperature range while remaining easy to administer orally.
3Stability of the object's composition
If non-aqueous liquid formulations are developed, then temperature stability and shelf-life are improved, but formulation complexity increases
Solution Approach 1:
The patent modifies key formulation parameters including solvent type (non-aqueous), pH level, and concentration to achieve temperature stability. By carefully adjusting these parameters, the formulation maintains stability across extreme temperatures while avoiding the need for complex stabilization systems or multiple components.
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 formulations maintain therapeutic plasma levels and pharmacodynamic responses comparable to injectable epinephrine, with improved stability across a wide temperature range and ease of use.
Implementation Method 1
stable, non-aqueous liquid formulations of epinephrine and its prodrugs... which can be administered orally via sprays, films, or drops
Implementation Method 2
dipivefrin, a prodrug of epinephrine
Data Source
AI summary
The disclosure provides stable liquid non-aqueous epinephrine and epinephrine prodrug formulations, including non-aqueous liquid dipivefrin HCl formulations. The formulations are suitable for use as oral spray, oral film, liquid-filled capsules or buccal, lingual, or sublingual drop formulation. The oral spray, oral film and liquid-filled capsule can be placed on the tongue, under the tongue (sublingual) or in the buccal space. Preferably, the oral spray is a sublingual spray. The disclosure provides a method for systemic delivery of a therapeutically effective amount of epinephrine to a subject comprising orally administering a non-aqueous liquid formulation of an epinephrine prodrug, such as dipivefrin HCl to the subject. The disclosure also includes a method of treatment of a disease amenable to treatment by in vivo delivery of systemic epinephrine comprising administering the disclosed formulations. The disease can be a respiratory disorder, type I allergic reactions including anaphylaxis and urticaria, or the disease can be cancer or a microbial infection.