Epinephrine Ophthalmic Composition Stability via Extraction

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Solution Overview

Problem

Commercially available epinephrine solutions for ophthalmological use often contain preservatives and sulfites, which can cause toxicity and lead to adverse reactions such as toxic anterior segment syndrome, necessitating the development of preservative- and sulfite-free alternatives for intraocular injections.

Innovation Solution

The development of lyophilized pharmaceutical compositions comprising therapeutically effective quantities of epinephrine and/or phenylephrine, combined with metal chelators like EDTA and optional anesthetics or NSAIDs, that are free of preservatives and sulfites, and are reconstituted immediately prior to use to maintain stability and safety.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If preservatives and sulfites are added to epinephrine solutions, then shelf life and stability are improved, but toxicity and adverse reactions increase

Engineering Contradiction:

Improveshelf lifeVSAvoidtoxicity

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent removes preservatives and sulfites from the epinephrine solution formulation, extracting the harmful components while retaining the therapeutic epinephrine. This is achieved through careful formulation that eliminates the need for these additives, thereby removing toxicity risks while maintaining shelf life through alternative stabilization methods.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces alternative stabilizing agents and packaging modifications as intermediaries to protect epinephrine from oxidation without using harmful preservatives. These intermediaries include modified packaging systems and alternative chemical stabilizers that do not cause toxicity, thereby maintaining stability while eliminating harmful effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Stability of the object's composition

If preservatives are used in epinephrine solutions, then stability is improved, but risk of toxic anterior segment syndrome increases

Engineering Contradiction:

ImprovestabilityVSAvoidtoxic anterior segment syndrome

Core Design Contradiction:

Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and eliminates preservatives from the formulation that are known to cause toxic anterior segment syndrome. By removing these harmful substances while maintaining stability through alternative means, the patent achieves stability without the risk of TASS.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the harmful effect of preservatives by finding alternative stabilizing mechanisms that provide the same protective function without the toxicity. This transforms the problem of needing preservatives into an opportunity to develop safer, non-toxic stabilization strategies.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Duration of action of stationary object

If epinephrine is stored for prolonged periods, then availability is improved, but oxidation and deactivation increase

Engineering Contradiction:

Improvestorage durationVSAvoidmedicinal properties

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent applies preliminary protective measures during formulation and packaging to prevent oxidation before storage begins. By pre-establishing protective mechanisms and using modified packaging that prevents exposure to oxidizing agents, the patent extends storage duration while maintaining medicinal properties.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent creates an inert environment for epinephrine storage by using modified packaging systems that exclude oxygen and other oxidizing agents. This inert atmosphere prevents oxidation during storage, thereby extending the shelf life while maintaining the reliability and medicinal properties of epinephrine.

Inventive Principle:

Principle #39Inert atmosphere (Inert environment)

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

These compositions provide effective and safe intraocular injections by eliminating toxicity risks while maintaining the medicinal properties of epinephrine, with stability extending beyond the typical shelf life of conventional epinephrine solutions.

Implementation Method 1

combined with metal chelators like EDTA

Methodology Applied

Scientific EffectChelation:

Implementation Method 2

lyophilized pharmaceutical compositions

Methodology Applied

Scientific EffectFreeze-drying: Freeze Drying

Data Source

PatentUS10285957B2Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof

Publication Date: 2019.05.14 HARROW IP LLC

AI summary

Pharmaceutical compositions for intraocular injection are described, the compositions comprise therapeutically effective quantity of lyophilized preservative-free and sulfite-free epinephrine or adrenaline and a metal chelator. Methods for fabricating the compositions and using them for intraocular injections are also described.