Mixed Micelle Compositions for Stable Water-Insoluble Vitamins
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Solution Overview
Problem
Existing methods for preparing pharmaceutical compositions with water-insoluble vitamins are unstable, require organic solvents, and involve costly explosion-proof installations, posing environmental and compliance challenges.
Innovation Solution
A pharmaceutical composition comprising mixed micelles with high ratios of water-insoluble vitamins (vitamin A, D, E, or K) to phospholipids and bile salts, prepared without organic solvents, using a method that includes dispersing phospholipids in water, adding bile salts, and optionally adjusting ratios for stability and freeze-drying.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the film method is used to prepare mixed micelles with water-insoluble vitamins, then the vitamins can be solubilized in organic solvents, but the intermediate material has limited stability and shelf-life
Solution Approach 1:
The patent changes the fundamental parameter of the preparation method from using organic solvents to using water as the sole solvent. This parameter change transforms the system from an organic-based film method to an aqueous-based direct mixing method, achieving both improved stability and simplified manufacturing without requiring complex drying or stabilization steps
Solution Approach 2:
The patent extracts and eliminates organic solvents from the formulation and manufacturing process. By removing this problematic component entirely and replacing it with water-soluble phospholipids and bile salts, the invention achieves stable mixed micelles without the stability issues and complex handling requirements associated with organic solvent-based systems
2Ease of manufacture
If volatile organic solvents are used in the preparation process, then the vitamins can be dissolved and formulated, but costly explosion proof installations are required and residual solvent levels must be minimized
Solution Approach 1:
The patent changes the solvent parameter from volatile organic solvents to water, fundamentally altering the safety profile of the manufacturing process. This parameter change eliminates explosion hazards while maintaining the ability to dissolve and formulate water-insoluble vitamins through the mixed micelle system formed by phospholipids and bile salts
Solution Approach 2:
The patent converts the traditionally harmful aspect of solvent use (volatility and flammability) into a benefit by selecting water as the solvent. Water's non-flammability and safety profile eliminate the need for expensive explosion-proof equipment while still achieving complete dissolution and formulation of lipophilic vitamins through the mixed micelle mechanism
3Manufacturing precision
If organic solvents are used for dissolution and drying, then the vitamins can be incorporated into mixed micelles, but residual organic solvent levels must be kept at a minimum to ensure compliance
Solution Approach 1:
The patent extracts and eliminates organic solvents from the entire manufacturing process, including dissolution and drying steps. By using water as the solvent and forming mixed micelles directly in aqueous solution, the invention achieves complete vitamin incorporation without any residual organic solvent, ensuring compliance with pharmaceutical guidelines and reducing environmental impact
Solution Approach 2:
The patent changes the solvent parameter from organic to aqueous, which fundamentally alters the compliance profile. Water-based formulations eliminate all concerns about residual organic solvent levels, ensuring automatic compliance with pharmaceutical regulations while maintaining effective vitamin incorporation through the mixed micelle system
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 achieves high stability and reduced excipient toxicity, lowering production costs and facilitating easier freeze-drying, while maintaining therapeutic efficacy without organic solvents.
Implementation Method 1
The mixed micelles comprising at least one phospholipid and at least one pharmaceutically acceptable bile salt
Implementation Method 2
Lecithin based mixed micelles have been used for the solubilization of poorly water-soluble (drug) substance(s)
Implementation Method 3
These products may then be reconstituted for use, e.g., in parenteral nutrition
Data Source
AI summary
The present disclosure relates to a pharmaceutical composition comprising mixed micelles, and at least one water-insoluble vitamin, as well as to a method for manufacturing said pharmaceutical composition and the use thereof; the mixed micelles comprising at least one phospholipid and at least one pharmaceutically acceptable bile salt.