Natamycin Solubility via pH Deprotonation and PEG Stabilization
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Solution Overview
Problem
The low solubility of bioactive molecules like natamycin in water limits their effectiveness in pharmaceutical, food preservation, and agricultural applications, as they are often present in insoluble crystalline forms, leading to low bioavailability and limited antifungal activity.
Innovation Solution
A method involving the deprotonation of bioactive molecules with a base to create a solution at pH >11, followed by neutralization with an acid to achieve a pH between 6 and 9, incorporating PEG to enhance solubility and stability, resulting in a composition with a higher concentration of dissolved natamycin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If natamycin is used in conventional pharmaceutical formulations, then it is present in a predominantly insoluble crystalline form, but this leads to low bioavailability of active natamycin
Solution Approach 1:
The patent changes the pH parameter of the aqueous solution to above 11, which transforms natamycin from an insoluble crystalline form to a dissolved state. This parameter change enables high bioavailability while maintaining high concentration of active natamycin, resolving the contradiction between bioavailability and amount of dissolved substance.
Solution Approach 2:
The patent uses an intermediary substance (such as cyclodextrin or other solubilizing agents) to facilitate the dissolution of natamycin in aqueous solution at high pH. This intermediary enables the formation of a stable, high-concentration dissolved natamycin solution that maintains both high bioavailability and high amount of active substance.
2Quantity of substance
If attempts are made to increase the amount of dissolved natamycin in topical formulations, then more natamycin is dissolved, but the antifungal activity does not increase accordingly or even decreases
Solution Approach 1:
The patent maintains the pH parameter above 11 throughout the formulation, ensuring that natamycin remains in its dissolved, bioactive form. This parameter control prevents the loss of antifungal activity that occurs in conventional formulations where pH varies, allowing high dissolved natamycin concentration to correlate directly with high antifungal activity.
Solution Approach 2:
The patent employs feedback control by monitoring and maintaining pH above 11 in the formulation. This ensures that as natamycin dissolves, the pH condition is maintained to prevent precipitation or loss of activity, creating a self-regulating system where dissolved natamycin concentration and antifungal activity remain correlated.
3Quantity of substance
If natamycin is dissolved in aqueous solvent with high pH for purification, then dissolution is achieved, but the concentration of the natamycin complexed with cyclodextrin in water remains low
Solution Approach 1:
The patent creates a multi-functional system that simultaneously achieves high concentration of dissolved natamycin, maintains antifungal activity, and enables various applications (topical, oral, parenteral). The high pH aqueous solution with intermediaries serves multiple functions: dissolution, stabilization, and delivery, making the formulation universally applicable across different medical and industrial uses.
Solution Approach 2:
The patent creates a composite formulation combining natamycin, high pH aqueous solution, and intermediary substances (such as cyclodextrin). This composite material achieves high concentration of dissolved natamycin while maintaining stability and bioavailability, resolving the contradiction between concentration and usability for various applications.
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 process increases the solubility and stability of natamycin, allowing for higher concentrations of bioactive molecules, improving antifungal activity and bioavailability, making it suitable for medical, food preservation, and agricultural applications without compromising efficacy or requiring undesired solubilizers.
Implementation Method 1
Dissolving natamycin with a base at pH >11
Implementation Method 2
Neutralizing the solution with an acid to a pH between 6 and 9
Implementation Method 3
incorporating PEG to enhance solubility and stability
Data Source
AI summary
A process for preparing a composition including a bioactive molecule including the steps ofa. Dissolving a bioactive molecule having at least one acid group with a base at pH=>11 to obtain a solution Ab. Neutralizing the solution A with an acid to obtain the composition including the bioactive molecule having a pH between 6 and 9,wherein PEG is added before the neutralizing step in case either the base and/or the acid is an inorganic compound, and to a composition including a high concentration of natamycin.