Solubilizing Composition for Water-Insoluble Drugs
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Solution Overview
Problem
Existing formulations for hardly water-soluble medical agents face challenges such as low intestinal absorbability and bioavailability due to low solubility, instability during storage, and limitations in drug form, particularly with high-pressure emulsification methods leading to decreased activity and precipitation issues.
Innovation Solution
A solubilizing composition comprising esters of oleic acid, triglycerides, polyoxyethylenesorbitan fatty acid esters, polyhydric alcohols, and acidic phospholipids, which self-emulsifies and maintains stability without water, allowing high concentration and effective dispersion of medical agents, suitable for various hardly water-soluble compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If high-pressure emulsification is used to reduce particle size, then particle size is reduced, but activity of the medical agent decreases due to friction heat
Solution Approach 1:
The patent replaces the mechanical high-pressure emulsification system with a self-emulsification system based on thermodynamic principles. The composition contains specific ratios of oil component (20-40%), surfactant (30-45%), and polyhydric alcohol (15-40%) that spontaneously form microemulsion without external mechanical energy input, thereby eliminating friction heat and preserving medical agent activity
Solution Approach 2:
The patent changes the composition parameters by specifying exact ranges of oil component (20-40%), surfactant (30-45%), and polyhydric alcohol (15-40%), along with controlled water content (0-60%). These parameter adjustments enable the system to achieve microemulsification through self-assembly rather than mechanical force, resolving the contradiction between particle size reduction and activity preservation
2Quantity of substance
If microemulsion is used for solubilization, then solubility is improved, but precipitation occurs during storage due to crystal growth
Solution Approach 1:
The patent maintains specific composition parameters: oil component 20-40%, surfactant 30-45%, polyhydric alcohol 15-40%, and water 0-60%. These parameter ranges create a thermodynamically stable microemulsion system where the medical agent remains solubilized during storage without crystal growth and precipitation
Solution Approach 2:
The patent creates a composite microemulsion system combining oil component, surfactant, polyhydric alcohol, and water in specific ratios. This composite structure provides both high solubility for hardly water-soluble medical agents and long-term storage stability by preventing crystal growth through the stabilizing effect of the polyhydric alcohol and surfactant
3Quantity of substance
If water is used as main component in microemulsion, then solubilization is achieved, but gelatin capsule film is dissolved and encapsulation is impossible
Solution Approach 1:
The patent controls water content to 0-60% (preferably 10-50%) rather than using water as the main component. This parameter adjustment allows the microemulsion to maintain solubilization capability while having low enough water content to prevent dissolution of gelatin capsule film, enabling encapsulation in soft capsules
4Shape
If heating at 160 to 180°C is applied for preparation, then emulsion is formed, but activity of common hardly water-soluble medical agent considerably decreases
Solution Approach 1:
The patent replaces thermal processing with a self-emulsification process that occurs at or near room temperature. The specific composition of oil component (20-40%), surfactant (30-45%), and polyhydric alcohol (15-40%) enables spontaneous microemulsion formation without heating, thereby preserving the activity of heat-sensitive medical agents
Solution Approach 2:
The patent creates a self-emulsifying system where the composition itself performs the emulsification function without external energy input. The amphiphilic structure of the surfactant and the solubilizing effect of polyhydric alcohol enable the system to self-assemble into microemulsion at ambient temperature, eliminating the need for high-temperature processing
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 intestinal absorbability and bioavailability by maintaining stability and enabling high concentration and self-emulsification, preventing precipitation and aggregation, and is applicable to a wide range of hardly water-soluble medical agents.
Implementation Method 1
a solubilizing pre-concentrate containing substantially no water... by containing (A) at least one oily component selected from esters of oleic acid with alcohols having 1 to 3 carbon atoms and triglycerides of fatty acids having 6 to 12 carbon atoms, (B) a polyoxyethylenesorbitan fatty acid ester, (C) a polyhydric alcohol which is liquid between 15° C. and 25° C., and (D) one or more acidic phospholipids
Implementation Method 2
there has been investigated solubilization using a thermodynamically stable microemulsion
Implementation Method 3
a polyhydric alcohol which is liquid between 15° C. and 25° C.
Data Source
AI summary
A solubilizing composition containing (A) at least one oily component selected from esters of oleic acid with alcohols having 1 to 3 carbon atoms and triglycerides of fatty acids having 6 to 12 carbon atoms, (B) a polyoxyethylenesorbitan fatty acid ester, (C) a polyhydric alcohol which is liquid between 15° C. and 25° C., and (D) one or more acidic phospholipids where the fatty acid constituting an acyl group thereof is selected from saturated fatty acids having 6 to 14 carbon atoms and unsaturated fatty acids having 16 to 18 carbon atoms, which contains 20 to 40% by weight of the component (A), 30 to 45% by weight of the component (B), 15 to 40% by weight of the component (C), and 0.5 to 4% by weight of the component (D), based on 100% by weight of a total amount of the components (A) to (D).