Protected Micelles for Stable Solubilization of Sparingly Soluble Ingredients
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Solution Overview
Problem
Existing formulations of sparingly water-soluble ingredients like fexofenadine face challenges in solubility, stability, and sterility, particularly in solutions like eye drops and nasal drops, due to precipitation and high production costs, making them impractical for widespread use.
Innovation Solution
The formation of micelles with anionic or cationic micelles protected by a specific protecting agent, such as polyethylene glycol or tyloxapol, enhances solubility and stability of sparingly water-soluble ingredients by forming stable micelles under pH conditions suitable for mucosal application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If a suspension formulation is used for sparingly water-soluble ingredients, then the ingredient can be delivered in solution form, but the formulation requires cumbersome preparation procedures and high facility investment
Solution Approach 1:
The patent changes the physical-chemical parameters of the ingredient by forming micelles through pH adjustment (anionization at basic pH) and adding protecting agents, transforming the ingredient from a suspension requiring mechanical dispersion to a stable molecular-level solution that can be sterilized by membrane filtration
Solution Approach 2:
The patent introduces protecting agents as intermediary substances that bind to the anionic micelles and prevent precipitation, enabling the ingredient to remain in solution form without requiring complex preparation procedures or high facility investment
2Quantity of substance
If cyclodextrin inclusion complexation is used to solubilize fexofenadine, then the ingredient solubility is improved, but massive precipitation occurs at room temperature or pH 6 to 7
Solution Approach 1:
The patent uses pH adjustment (basic conditions for anionization) and adding protecting agents as parameter changes that prevent the precipitation problem. The protecting agents bind to the anionic micelles and maintain solubility at physiological pH levels, overcoming the fatal drawback of precipitation at room temperature or pH 6 to 7
Solution Approach 2:
The protecting agent acts as an intermediary that binds to the anionic micelles formed from fexofenadine, preventing aggregation and precipitation. This intermediary substance enables the solution to remain stable at physiological pH levels, solving the precipitation problem inherent in cyclodextrin inclusion complexation
3Reliability
If suspensions are used for sparingly water-soluble ingredients, then the ingredient can be formulated, but the suspensions cannot be sterilized by membrane filtration
Solution Approach 1:
The patent changes the formulation from a suspension to a molecular-level solution through micelle formation at basic pH followed by acidification to physiological pH. This parameter change enables the formulation to be sterilized by membrane filtration, ensuring sterility and quality without compromising ingredient delivery
4Quantity of substance
If anionic micelles are formed from sparingly water-soluble ingredients, then solubility is improved, but the micelles are not stable at physiological pH
Solution Approach 1:
The protecting agent serves as an intermediary that binds to the anionic micelles formed at basic pH and maintains their stability at physiological pH levels. This intermediary substance enables the micelles to remain stable and prevent precipitation throughout the pH range of 5 to 9, ensuring long-term storage stability
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 micelle formation maintains the solubility and stability of sparingly water-soluble ingredients, preventing precipitation and ensuring pharmaceutical efficacy in solutions over time, suitable for eye drops and nasal drops.
Implementation Method 1
the protecting agent has an atom bound to an anionized functional group of the anionic micelle, and the electron density of said atom is smaller than the electron density of the anionized functional group of the anionic micelle
Implementation Method 2
a sparingly water-soluble ingredient can be solubilized by producing a micelle in which an anionic or cationic micelle formed from the sparingly water-soluble ingredient as a structural unit is protected by a protecting agent
Data Source
AI summary
The present invention provides a micelle comprising an anionic micelle and a protecting agent surrounding the anionic micelle, the anionic micelle being formed from, as a structural unit, an ingredient that has a functional group capable of being anionized under basic conditions and has anionic micelle-forming ability, the protecting agent protecting the anionic micelle. The present invention also provides a micelle comprising a cationic micelle and a protecting agent surrounding the cationic micelle, the cationic micelle being formed from, as a structural unit, an ingredient that has a functional group capable of being cationized under acidic conditions and has cationic micelle-forming ability, the protecting agent protecting the cationic micelle.