Ionic Liquid API Salts for Stable Incompatible Formulations
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Solution Overview
Problem
Softgel capsules face stability and solubility issues due to the degradation and incompatibility of active pharmaceutical ingredients (APIs) in liquid fills, leading to formulation challenges and high failure rates.
Innovation Solution
The use of alkali metal salts for at least one API, combined with a chemically incompatible second API, stabilizes the mixture by ionization, reducing reactivity and enhancing solubility, even at less than 100% ionization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If incompatible APIs are combined in liquid fill, then dispersal speed is improved, but stability deteriorates
Solution Approach 1:
The patent changes the chemical state of the first API from neutral to ionized form by combining it with an alkali metal salt. This parameter change in chemical state eliminates the harmful interaction between incompatible APIs while preserving the liquid fill formulation, thereby maintaining both fast dispersal and stability.
Solution Approach 2:
The alkali metal salt acts as an intermediary substance that mediates between the first API and the second API. By introducing this intermediary, the harmful chemical interaction between incompatible APIs is prevented, allowing stable coexistence in the liquid fill while maintaining rapid dispersal characteristics.
2Adaptability or versatility
If incompatible APIs are combined in liquid fill, then dosage form flexibility is improved, but solubility deteriorates
Solution Approach 1:
The patent changes the solubility parameter of the first API by converting it to an ionized form through combination with alkali metal salt. This parameter change enables the API to maintain high solubility in the liquid fill even when combined with chemically incompatible second APIs, thus preserving dosage form flexibility.
Solution Approach 2:
The alkali metal salt serves as an intermediary that facilitates the solubility of the first API in the presence of incompatible second APIs. This intermediary enables the maintenance of adequate solubility levels while allowing formulation flexibility in combining multiple APIs.
3Device complexity
If conventional API combination is used, then formulation simplicity is maintained, but stability deteriorates over time
Solution Approach 1:
The patent introduces a parameter change in the chemical state of the first API by using alkali metal salt combination. This change extends the duration of stability over months while maintaining relatively simple formulation requirements, effectively resolving the time-dependent stability issue.
Solution Approach 2:
The alkali metal salt acts as a stabilizing intermediary that prevents degradation reactions between incompatible APIs over extended periods. This intermediary enables the formulation to maintain stability over months without requiring complex protective measures.
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
Stable and soluble combinations of otherwise incompatible APIs are achieved, maintaining stability and solubility over extended periods, suitable for softgel capsules and other liquid or solid dosage forms.
Implementation Method 1
The use of alkali metal salts for at least one API, combined with a chemically incompatible second API, stabilizes the mixture by ionization, reducing reactivity and enhancing solubility
Implementation Method 2
The use of alkali metal salts for at least one API, combined with a chemically incompatible second API, stabilizes the mixture by ionization, reducing reactivity and enhancing solubility
Data Source
AI summary
A composition comprises an alkali metal salt of a first pharmaceutical ingredient; and a second pharmaceutical ingredient, wherein the second pharmaceutical ingredient is chemically incompatible with the first pharmaceutical ingredient, and the composition is an aqueous solution. The first active pharmaceutical ingredient can comprise ibuprofen or naproxen. The second pharmaceutical ingredient can comprise acetaminophen.