Tranexamic Acid Solubility via Low-pH Concentration Adjustment
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Solution Overview
Problem
The low solubility of tranexamic acid in water limits the concentration of available liquid dosage forms, making it difficult to achieve higher dosages needed for enhanced bleeding control during surgeries or other conditions.
Innovation Solution
A method involving the initial dissolution of tranexamic acid in water, adjusting pH with a strong acid to a specific range (e.g., below pH 4.5), and iteratively adding tranexamic acid to reach desired concentrations up to 400 mg/mL, using acids like hydrochloric acid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If tranexamic acid is dissolved in water at standard conditions, then the solution can be prepared, but the concentration is limited to about 167 mg/mL due to low solubility
Solution Approach 1:
The patent applies parameter changes by adjusting the pH value of the aqueous solution to below 4.5 using strong acids (hydrochloric, perchloric, sulfuric, nitric, hydrobromic, hydroiodic, chloric, or phosphoric acid). This pH modification fundamentally changes the solubility parameters of tranexamic acid, enabling concentrations up to 400 mg/mL that exceed the standard solubility limit of 167 mg/mL at neutral pH
2Quantity of substance
If higher concentrated dosages of tranexamic acid are needed for urgent bleeding control, then the therapeutic effect is improved, but the available liquid dosage forms cannot provide such concentrations due to solubility limits
Solution Approach 1:
The patent resolves the manufacturing challenge by changing the pH parameter during the liquid dosage form preparation process. By adjusting pH to below 4.5 in the manufacturing stage, high concentration solutions (up to 400 mg/mL) can be directly prepared without requiring complex formulation techniques or post-processing steps
3Quantity of substance
If pH is lowered to increase solubility of tranexamic acid, then the concentration can be increased, but the pH value decreases below normal range
Solution Approach 1:
The patent intentionally changes the pH parameter to below 4.5 as a controlled condition to achieve enhanced solubility. The method accepts this pH change as a necessary parameter modification, and the resulting low-pH stable solution becomes the desired final product state for high-concentration liquid dosage forms
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
This method significantly increases the solubility of tranexamic acid, allowing for stable, highly concentrated liquid dosage forms with concentrations up to 400 mg/mL, maintaining stability and shelf-life under accelerated conditions.
Implementation Method 1
Addition of a strong acid (that dissociates completely in water) to the solution obtained in Step (a) and simultaneously monitoring the decrease in the pH value of the solution
Implementation Method 2
lowering the pH value of the solution to below pH 4.5, thereby increasing solubility of tranexamic acid
Data Source
AI summary
A method for enhancing solubility of tranexamic acid comprising the following steps:a) Initially dissolving tranexamic acid in water;b) Measuring a pH value of the solution obtained in Step (a);c) Addition of a strong acid (that dissociates completely in water) to the solution obtained in Step (a) and simultaneously monitoring the decrease in the pH value of the solution until approximately pH 4.5 or less than pH 4.5 is reached, to increase solubility of tranexamic acid;d) Addition of tranexamic acid to reach the pH value of the solution obtained in Step (c) above the pH 2.0; ande) Repeating Steps (c) and (d) until a desired amount of tranexamic acid is added to the solution of Step (a), that is a desired concentration of tranexamic acid in the final solution is reached.