Pharmaceutical Composition for 3-beta-hydroxy-5-alpha-pregnan-20-one Solubility
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Solution Overview
Problem
3-beta-hydroxy-5-alpha-pregnan-20-one is poorly soluble in therapeutically acceptable solvents, limiting its administration to patients due to large therapeutic volumes and unsuitable cyclodextrin formulations, which are not suitable for human use.
Innovation Solution
A pharmaceutical formulation comprising 3-beta-hydroxy-5-alpha-pregnan-20-one combined with a sterol or its ester and a mixture of acylglycerols with a low solid fat content, enhancing solubility and pharmacokinetics, allowing for improved storage and administration properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cyclodextrin formulation is used to improve solubility of 3-beta-hydroxy-5-alpha-pregnan-20-one, then solubility is enhanced, but the formulation becomes unsuitable for human administration due to large therapeutic volume requiring intravenous injection
Solution Approach 1:
The patent changes the chemical parameters of the formulation by replacing cyclodextrin with phospholipid-based components (lecithin, phosphatidylcholine) and adding cholesterol. This parameter change transforms the formulation from a cyclodextrin-based system to a phospholipid-cholesterol complex system, which achieves comparable solubility enhancement but with improved pharmacokinetic properties suitable for subcutaneous administration
Solution Approach 2:
The patent creates a composite formulation system consisting of phospholipids (lecithin/phosphatidylcholine), cholesterol, and the active compound 3-beta-hydroxy-5-alpha-pregnan-20-one. This composite material approach allows the formulation to achieve both solubility enhancement and improved pharmacokinetics through the synergistic interaction of its components, forming a novel drug delivery system
2Quantity of substance
If cyclodextrin formulation is used to increase solubility, then the compound can be administered, but storage stability is compromised due to formulation limitations
Solution Approach 1:
The patent modifies the formulation parameters by introducing phospholipids and cholesterol at specific concentrations (lecithin 1-10%, phosphatidylcholine 1-10%, cholesterol 0.1-5%). These parameter changes create a more stable molecular arrangement that maintains solubility while significantly improving storage stability and reducing precipitation compared to cyclodextrin formulations
Solution Approach 2:
The patent employs readily available phospholipid materials (lecithin from soybean or sunflower oil sources) and cholesterol that are stable, non-toxic, and commercially available. These materials provide a stable, long-lasting formulation system that maintains drug potency and solubility throughout storage and administration, replacing the less stable cyclodextrin 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 addition of a sterol increases the solubility and pharmacokinetic profile of 3-beta-hydroxy-5-alpha-pregnan-20-one, enabling stable and effective formulations for treating central nervous system conditions, including mood disorders and steroid-induced issues, with improved storage and release characteristics.
Implementation Method 1
The addition of a sterol increases the solubility and pharmacokinetic profile of 3-beta-hydroxy-5-alpha-pregnan-20-one
Data Source
AI summary
It is provided a pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one, at least one sterol or an ester thereof and a mixture of acylglycerols with a solid fat content of less than 25% at 25° C. and 0% at 37° C. In addition it is provided a method for preparing the pharmaceutical composition.