Tranexamic Acid Composition Stabilization via pH Buffering

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Solution Overview

Problem

Tranexamic acid compositions are unstable and prone to coloration during storage, leading to a lack of commercially available storage-stable liquid oral formulations, with existing stabilization methods being incomplete or ineffective against coloration caused by sweetening agents.

Innovation Solution

Incorporating specific pH buffering agents like Tris and glycine in a weight ratio of 100:1 to 2:1 with tranexamic acid, maintaining a pH range of 6 to 8, which stabilizes and prevents coloration even in the presence of coloration-promoting agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional stabilizing agents (antioxidants) are added to tranexamic acid compositions, then colouration is prevented to some extent, but the compositions remain unstable and develop unpleasant taste upon storage

Engineering Contradiction:
Improvestability of tranexamic acid compositionVSAvoidcolouration and unpleasant taste
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The patent changes the pH parameter of the composition by using pH buffering agents (Tris or glycine) to maintain pH between 6-8. This parameter change stabilizes tranexamic acid and prevents colouration and taste degradation without requiring additional stabilizing agents, directly resolving the technical contradiction

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces pH buffering agents (Tris or glycine) as intermediary substances that mediate between tranexamic acid and the harmful effects of colouration and taste degradation. These buffering agents stabilize the composition by maintaining optimal pH conditions, preventing the formation of coloured and unpleasant-tasting degradation products

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If sweetening agents are added to improve palatability, then the composition becomes more acceptable for oral use, but colouration is promoted and stability is reduced

Engineering Contradiction:
Improvepalatability of oral rinseVSAvoidstorage stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

By changing the pH parameter to between 6-8 through pH buffering agents, the patent creates an environment where tranexamic acid remains stable even in the presence of sweetening agents. This parameter optimization prevents the interaction between sweetening agents and tranexamic acid that would otherwise lead to colouration and degradation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary anti-action by using pH buffering agents to preemptively prevent the colouration and degradation reactions that would be caused by sweetening agents. The buffering agents establish a stable pH environment before any degradation can occur, counteracting the harmful effects of sweetening agents on stability

Inventive Principle:
Principle #9Preliminary anti-action

3Duration of action of stationary object

If tranexamic acid compositions are stored for prolonged periods, then they provide sustained therapeutic availability, but they undergo colouration and instability

Engineering Contradiction:
Improveshelf lifeVSAvoidcolouration and instability
Core Design Contradiction:
Duration of action of stationary objectVSObject-generated harmful factors

Solution Approach 1:

The patent optimizes the pH parameter to between 6-8 using pH buffering agents, which creates a stable environment that prevents colouration and degradation during prolonged storage. This parameter control allows the composition to maintain both extended shelf life and stability, resolving the contradiction between duration and stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The pH buffering agents (Tris or glycine) provide self-service stability to the composition, maintaining pH within the optimal range automatically during storage without requiring additional stabilizing agents or antioxidants. This self-regulating system prevents colouration and instability over extended storage periods

Inventive Principle:
Principle #25Self-service

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 composition remains stable and colorless for at least 6 months, with negligible absorbance at 420 nm, eliminating the need for additional stabilizing agents and enhancing shelf life, thus enabling commercial use as a stable oral rinse.

Implementation Method 1

certain pH buffering agents, in addition to maintaining the pH of tranexamic acid compositions in the desired range, preferably in the range of 6 to 8, are capable of imparting stability and resistance to colouration of tranexamic acid solutions over a prolonged period of time

Methodology Applied
Scientific EffectpH buffering:

Data Source

PatentEP2695605B1Tranexamic acid composition
Publication Date: 2017.05.03 PARAPHARM DEV LTD

AI summary

The present invention relates to a storage-stable liquid composition comprising tranexamic acid as an active ingredient and a pH buffering agent having the formula H2N(CH2)kX, wherein X is CR3 or CO2H, k is 0 or 1, and wherein R represents a hydroxyalkyl group. The composition is essentially colour-free and stable.