Multivesicular Liposome Formulations for Tranexamic Acid Sustained Release

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Solution Overview

Problem

Tranexamic acid (TXA) administration, particularly through oral or intravenous routes, often results in side effects such as gastrointestinal discomfort and rapid plasma level fluctuations, leading to sub-therapeutic levels due to rapid excretion and metabolism, necessitating a stable, sustained release formulation for both topical and parenteral applications.

Innovation Solution

Multivesicular liposomes (MVLs) encapsulating TXA, comprising a lipid component with amphipathic and neutral lipids, along with pH modifying agents, providing a sustained release profile while allowing for both immediate and prolonged therapeutic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If TXA is administered as a bolus dose to provide necessary clotting effect, then immediate therapeutic effect is achieved, but rapid plasma level increase causes side effects such as gastrointestinal discomfort and dizziness

Engineering Contradiction:

Improveonset of therapeutic effectVSAvoidside effects

Core Design Contradiction:

SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent segments the drug delivery system into multivesicular liposomes containing multiple internal chambers, where TXA is encapsulated within these chambers. This segmentation allows for controlled release of TXA over time, providing both immediate therapeutic effect through initial plasma levels and sustained release to maintain therapeutic levels without causing rapid plasma level spikes that lead to side effects

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The multivesicular liposome acts as an intermediary carrier between the administered TXA and the plasma. The liposome structure with its lipid bilayer membranes and internal chambers mediates the release of TXA, preventing direct bolus administration and the associated rapid plasma level increases while still delivering the necessary therapeutic effect

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If TXA is administered to achieve sustained therapeutic levels, then efficacy is maintained, but rapid excretion and metabolism cause plasma levels to quickly reach sub-therapeutic amounts

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidduration of therapeutic effect

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The multivesicular liposome formulation provides continuous release of TXA through its multiple internal chambers. As TXA is released from the liposomes, it maintains sustained therapeutic levels in plasma, counteracting the rapid excretion and metabolism that would otherwise cause plasma levels to quickly drop to sub-therapeutic amounts

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The liposome structure is pre-designed with multiple internal chambers that contain TXA, preparing the drug for controlled release. This preliminary structuring ensures that TXA is delivered in a sustained manner, maintaining therapeutic efficacy over an extended period despite rapid metabolic clearance

Inventive Principle:

Principle #10Preliminary action

3Duration of action of moving object

If sustained release formulation is developed to prolong therapeutic effect, then duration of action is improved, but formulation complexity increases

Engineering Contradiction:

Improveduration of therapeutic effectVSAvoidformulation complexity

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent employs a nested structure where multiple internal chambers are contained within the multivesicular liposome, which itself is enclosed by an external membrane. This nesting of chambers within chambers provides a sophisticated sustained release mechanism while maintaining a relatively simple overall formulation structure that can be administered through conventional routes

Inventive Principle:

Principle #7Nested doll (Nesting)

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 MVL formulation minimizes side effects, maintains or improves efficacy, and prolongs the therapeutic effect of TXA, offering a stable and controlled release of the drug, suitable for various administration routes including subcutaneous injection and wound infiltration.

Implementation Method 1

multivesicular liposomes (MVLs) encapsulating TXA

Methodology Applied

Scientific EffectEncapsulation: Physical Containment

Implementation Method 2

sustained release profile

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 3

one or more pH modifying agents

Methodology Applied

Scientific EffectpH modification:

Data Source

PatentEP3142656B1Multivesicular liposome formulations of tranexamic acid

Publication Date: 2018.10.17 PACIRA PHARMA INC

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AI summary

Some embodiments of the present application are related to multivesicular liposome formulations comprising tranexamic acid (TXA) for the purpose of minimizing the side effects of unencapsulated tranexamic while maintaining or improving efficacy and lengthening the duration of the effect. Methods of making and administering the tranexamic acid encapsulated multivesicular liposome formulations and their use as medicaments are also provided.