Multivesicular Liposome NSAID Formulation for Joint Delivery

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Solution Overview

Problem

Current NSAID therapies for pain and inflammation are limited by gastrointestinal toxicity and require high systemic doses to achieve efficacious levels at the synovial site, leading to side effects and increased costs.

Innovation Solution

Development of multivesicular liposome formulations encapsulating NSAIDs, which provide sustained release and direct delivery to the joint synovial cavity, reducing systemic exposure and side effects while maintaining therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high systemic doses of NSAIDs are administered to achieve efficacious levels at the synovial site, then therapeutic efficacy is improved, but gastrointestinal toxicity and side effects increase

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidgastrointestinal toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses multivesicular liposomes as an intermediary delivery system to transport NSAIDs directly to the synovial cavity. The liposomal formulation acts as a mediator that bypasses the gastrointestinal tract and systemic circulation, delivering the drug directly to the target site while minimizing exposure to healthy tissues

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention implements local quality by concentrating the NSAID delivery specifically at the synovial cavity rather than distributing it systemically. The multivesicular liposomes are designed to release drugs locally at the injection site, creating high local concentrations where needed while maintaining low systemic levels

Inventive Principle:
Principle #3Local quality

2Quantity of substance

If high systemic doses of NSAIDs are administered, then drug levels at the synovial site are improved, but systemic exposure and side effects increase

Engineering Contradiction:
Improvedrug levels at synovial siteVSAvoidsystemic exposure
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent segments the drug delivery process into distinct compartments using multivesicular liposomes with multiple internal vesicles. This segmentation allows the drug to be contained and released in a controlled manner at the target site, preventing premature systemic distribution and reducing overall systemic exposure while maintaining adequate local concentrations

Inventive Principle:
Principle #1Segmentation

3Ease of operation

If oral NSAID therapy is used, then ease of administration is improved, but gastrointestinal complications increase

Engineering Contradiction:
Improveease of administrationVSAvoidgastrointestinal complications
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The multivesicular liposome formulation serves as an intermediary that changes the route of administration from oral to intraarticular injection. This intermediary delivery system eliminates direct contact with the gastrointestinal tract, thereby preventing gastrointestinal complications while still providing effective drug delivery to the synovial cavity

Inventive Principle:
Principle #24Intermediary (Mediator)

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 multivesicular liposome formulations achieve prolonged drug release, reducing gastrointestinal toxicity and side effects, allowing for lower doses and more effective pain relief with fewer systemic toxicities, thereby enhancing the economic viability of NSAID therapy.

Implementation Method 1

The in vitro release profiles demonstrated that both formulations released >80% of the encapsulated drug within 72 h, with the chitosan-TPGS MVLs showing a more sustained release pattern compared to the commercial suspension

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

The in vitro release profiles demonstrated that both formulations released >80% of the encapsulated drug within 72 h, with the chitosan-TPGS MVLs showing a more sustained release pattern

Methodology Applied
Scientific EffectErosion:

Implementation Method 3

remote loading a non-steroidal anti-inflammatory drug into said multivesicular liposomes, wherein a gradient of low pH outside the MVL to high pH inside the MVL is present to drive the NSAID into the MVL

Methodology Applied
Scientific EffectpH gradient driven transport:

Data Source

PatentUS10729651B2Sustained release formulation of a non-steroidal anti-inflammatory drug
Publication Date: 2020.08.04 PACIRA PHARMA INC

AI summary

Disclosed are formulations comprising multivesicular liposomes and one or more non-steroidal anti-inflammatory drugs which minimize the side effects of unencapsulated non-steroidal anti-inflammatory drugs while maintaining or improving efficacy. Methods of making and administering the formulations comprising multivesicular liposomes and one or more non-steroidal anti-inflammatory drugs and their use as medicaments are also provided.