Injectable Semi-Solid Gel Bupivacaine Formulations for 72-Hour Release

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Solution Overview

Problem

Existing local anesthetic formulations suffer from initial burst release, inconsistent drug release kinetics, and high manufacturing complexity, leading to inadequate pain management post-surgery, particularly in the first 24 hours, and contribute to the opioid epidemic.

Innovation Solution

A semi-solid gel formulation comprising castor oil and a gelling agent, such as SUPPOCIRE DM, with a specific ratio and viscosity, solubilizing bupivacaine and optional anti-inflammatory agents, providing a controlled and prolonged release of bupivacaine for at least 72 hours without significant burst.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If local anesthetic is administered systemically to manage postoperative pain, then pain relief is achieved, but opioid addiction and misuse increase

Engineering Contradiction:
Improvepain relief effectivenessVSAvoidopium epidemic and addiction
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a lipid-based semi-solid gel as an intermediary vehicle to deliver bupivacaine locally at the surgical site. This gel formulation acts as a mediator between the anesthetic drug and the target tissue, enabling controlled local release while avoiding systemic opioid administration. The gel matrix controls drug release kinetics, providing sustained analgesia without contributing to the opioid epidemic.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If conventional local anesthetic formulations are used, then initial pain relief is provided, but duration of action is less than 12 hours

Engineering Contradiction:
Improveinitial pain reliefVSAvoidanalgesia duration
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The patent changes the physical and chemical parameters of the anesthetic formulation by using a lipid-based semi-solid gel matrix instead of conventional aqueous solutions. This parameter change in the delivery vehicle enables sustained release of bupivacaine over 72 hours or longer, extending the duration of action from less than 12 hours to multiple days while maintaining effective pain relief.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of moving object

If liposomal bupivacaine (EXPAREL) is used to prolong release, then manufacturing complexity increases

Engineering Contradiction:
Improvedrug release durationVSAvoidmanufacturing complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent simplifies the formulation approach by changing from complex liposomal encapsulation to a lipid-based semi-solid gel matrix. This parameter change in the delivery system achieves comparable or superior sustained release (72 hours or longer) with significantly reduced manufacturing complexity, avoiding the need for sophisticated liposome preparation and stabilization processes.

Inventive Principle:
Principle #35Parameter changes

4Duration of action of moving object

If polymeric matrices are used for controlled release, then burst release occurs leading to systemic toxicity

Engineering Contradiction:
Improveprolonged drug releaseVSAvoidsystemic toxicity
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material basis from synthetic polymeric matrices to a lipid-based semi-solid gel system. This parameter change in the delivery vehicle eliminates the burst release phenomenon and associated systemic toxicity while maintaining prolonged drug release. The lipid matrix provides more controlled and sustained bupivacaine release over 72 hours or longer without toxic effects.

Inventive Principle:
Principle #35Parameter changes

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 achieves rapid pain relief with sustained analgesia for 72 hours, reduces the need for systemic opioids, and is easily administered through small needles with minimal pain, offering a cost-effective and reliable solution for post-surgical pain management.

Implementation Method 1

The drug delivery vehicle typically consists of a polymeric matrix from which drug is released by diffusion and/or degradation of the matrix

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

Incorporation of anhydride bonds (which undergo hydrolysis) in the polymer backbone rendered the formulation biodegradable

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 3

A semi-solid gel formulation comprising castor oil and a gelling agent, such as SUPPOCIRE DM, with a specific ratio and viscosity

Methodology Applied
Scientific EffectGelation: Gel

Data Source

PatentEP3720420B1Injectable long-acting local anesthetic semi-solid GEL formulations
Publication Date: 2025.08.27 HUZHOU HUI ZHONG JI SHI BIOTECHNOLOGY CO LTD
  • EP3720420B1 patent drawingFigure 1~2
  • EP3720420B1 patent drawingFigure 3~4
  • EP3720420B1 patent drawingFigure 5~5a

AI summary

What is disclosed is a controlled release pharmaceutical composition comprising a biocompatible and bioerodible semi-solid gel comprising a triglyceride of ricinoleic acid, a gelling agent, bupivacaine and, optionally, a corticosteroid, an analgesic, or an anti-inflammatory agent.