Self-Emulsifying EPA-E and Statin Composition
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Solution Overview
Problem
There is a demand for a pharmaceutical composition containing eicosapentaenoic acid ethyl ester (EPA-E) and a statin, such as pitavastatin or rosuvastatin, that offers a single dose administration, excellent self-emulsifying properties, stability, and reduced side effects, while maintaining high absorption and adherence, and minimizing ethanol and polyhydric alcohol content.
Innovation Solution
A pharmaceutical composition comprising 70-90% EPA-E, 0.5-6% water, 1-29% polyoxyethylene sorbitan fatty acid ester, 1-25 parts lecithin, and pitavastatin or rosuvastatin, with up to 4% ethanol and 4% polyhydric alcohol, which forms a stable self-emulsifying system, enhancing absorption and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If EPA-E is orally administered under fasting, then absorption requires secretion of bile acid and food components as carrier, but increase in plasma EPA concentration is smaller compared to administration after meal
Solution Approach 1:
The patent applies preliminary action by pre-formulating EPA-E with emulsifiers and other components to create a self-emulsifying composition. This preparation is done in advance to enable the composition to spontaneously form emulsions in the gastrointestinal tract without requiring food components or bile acid secretion, thus solving the problem of poor absorption under fasting conditions while achieving high plasma EPA concentration
Solution Approach 2:
The patent uses emulsifiers as intermediary substances to facilitate the absorption of EPA-E. These emulsifiers act as mediators between the hydrophobic EPA-E and the aqueous gastrointestinal environment, enabling efficient absorption under fasting conditions without requiring food components as carriers
2Ease of operation
If a composition containing EPA-E and statin is developed, then medication adherence is improved by single dose administration, but interaction between medicinal components, solubility, and stability problems arise
Solution Approach 1:
The patent applies parameter changes by carefully controlling the composition ratios of EPA-E, statin, emulsifiers, and other components. By optimizing these parameters within specific ranges, the patent achieves a formulation that maintains stability while enabling single-dose administration of both medicinal components
Solution Approach 2:
The patent uses composite materials by combining EPA-E, statin, emulsifiers, and other components into a single self-emulsifying composition. This composite formulation addresses the challenges of component interaction and solubility while maintaining stability and enabling convenient single-dose administration
3Object-affected harmful factors
If self-emulsifying composition with low ethanol content is used, then safety is improved, but self-emulsifying property and oral absorption may be compromised
Solution Approach 1:
The patent applies parameter changes by reducing ethanol content to 4% or less while compensating for the reduced self-emulsifying capability through the addition of emulsifiers and optimization of other composition parameters. This maintains safety while preserving adequate self-emulsifying property
Solution Approach 2:
The patent introduces emulsifiers as intermediary substances to replace the self-emulsifying function that would otherwise be provided by higher ethanol content. These emulsifiers mediate the formation and stabilization of emulsions, enabling low ethanol content while maintaining reliable self-emulsifying property
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 allows for efficient absorption of EPA-E and pitavastatin/rosuvastatin, maintaining stability and appearance under various temperatures, reducing side effects, and improving medication adherence with a single daily dose.
Implementation Method 1
A composition containing eicosapentaenoic acid ethyl ester, water, polyoxyethylene sorbitan fatty acid ester, lecithin, and pitavastatin or rosuvastatin, or a salt thereof, or a composition obtained by encapsulating said composition
Implementation Method 2
a composition containing a ω3 PUFA, a particular statin, and a particular ionic emulsifier has been reported
Data Source
AI summary
A pharmaceutical composition comprising, in relation to 100% by weight of a total amount of a self-emulsifying composition, 70 to 90% by weight of eicosapentaenoic acid ethyl ester as a first medicinal component, 0.5 to 6% by weight of water, 1 to 29% by weight of polyoxyethylene sorbitan fatty acid ester (optionally further comprising polyoxyethylene castor oil) as an emulsifier, 1 to 25 parts by weight of lecithin in relation to 100 parts by weight of the eicosapentaenoic acid ethyl ester, and pitavastatin, rosuvastatin, or a salt thereof as a second medicinal component. The composition is excellent in any one of self-emulsifying property, dispersibility of the composition, emulsion stability, absorbability, and storage stability of the medicinal components and a preparation.