Lidocaine Epinephrine Formulation Stability via pH Adjustment
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Solution Overview
Problem
Prolonged shortages of Lidocaine with Epinephrine 1:100,000 have created a need for a stable, ready-to-use liquid formulation comprising lidocaine hydrochloride and epinephrine hydrochloride, which is not easily available in a form suitable for immediate use, particularly in medical procedures requiring local anesthesia.
Innovation Solution
A ready-to-use liquid formulation comprising lidocaine hydrochloride (10 mg/mL or 20 mg/mL), epinephrine hydrochloride (10 mcg/mL), sodium chloride, sodium metabisulfite, citric acid, EDTA sodium, and sterile water, with a pH adjuster to maintain a pH of 3.4, packaged in light-resistant containers to ensure stability and potency, and a process for preparing this formulation involving dissolving components in sterile water and filtering to prevent oxidation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If nitrogen gas is used to stabilize epinephrine in multi-dose vials, then epinephrine stability is improved, but device complexity and preparation complexity increase
Solution Approach 1:
The patent removes the nitrogen gas requirement from the formulation system entirely. Instead of using nitrogen gassing to prevent oxidation, the invention uses a pH-adjusted formulation with metabisulfite and EDTA that stabilizes epinephrine without requiring inert atmosphere manipulation, thereby eliminating the complexity of multi-dose vial preparation.
Solution Approach 2:
The patent changes the pH parameter to 3.4 (acidic conditions) which fundamentally alters the stability mechanism. At this specific pH, epinephrine is stabilized through chemical interaction with metabisulfite and EDTA rather than physical exclusion of oxygen, allowing the formulation to be stable without nitrogen gassing.
2Ease of operation
If ready-to-use syringe formulation is developed, then ease of operation is improved, but manufacturing precision and formulation stability control become more difficult
Solution Approach 1:
The patent performs all stabilization actions in advance during formulation manufacturing. Metabisulfite and EDTA are pre-added to create a stable formulation that maintains epinephrine potency without requiring nitrogen gassing or complex storage conditions. This preliminary stabilization allows the syringe to be ready-to-use while maintaining manufacturing precision through controlled formulation parameters.
3Loss of substance
If extended shelf life is achieved without nitrogen gas, then loss of substance is reduced, but reliability of stability maintenance becomes more challenging
Solution Approach 1:
The patent introduces metabisulfite and EDTA as intermediary stabilizing agents that mediate between epinephrine and oxygen. These agents prevent oxidation of epinephrine through chemical interaction, creating a reliable stability mechanism that does not depend on physical exclusion of oxygen. This intermediary approach maintains reliability over extended periods without nitrogen gas.
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 formulation maintains the potency of lidocaine and epinephrine at 90% or higher for 1.5 to 3 months at 25°C, even in the presence of air, providing a stable and effective anesthetic solution for procedural analgesia, such as venipuncture and punch biopsies, with extended shelf life without the need for nitrogen gas to stabilize epinephrine.
Implementation Method 1
a process for preparing this formulation involving dissolving components in sterile water and filtering to prevent oxidation
Implementation Method 2
with a pH adjuster to maintain a pH of 3.4
Implementation Method 3
packaged in light-resistant containers to ensure stability and potency
Data Source
AI summary
Disclosed herein is a ready-to-use liquid formulation comprising lidocaine hydrochloride and epinephrine hydrochloride. Also disclosed herein is a process for preparing a ready-to-use liquid formulation comprising lidocaine hydrochloride and epinephrine hydrochloride, as well as methods for using the ready-to-use liquid formulation.