Anionic Bioactive Excipients Overcome Solubility Limits
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Solution Overview
Problem
The 'Rule of Five' limits the solubility of hydrophobic bioactive molecules in bodily fluids, restricting their bioavailability due to an octanol-water partition coefficient greater than 5, which existing strategies have not effectively overcome.
Innovation Solution
Converting hydrophobic bioactive molecules into anionic forms using simple acid/base chemistry, which can improve their octanol-water partition coefficients, allowing them to be administered and revert back to their parent molecules, thereby overcoming the solubility limitations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Force
If hydrophobic bioactive molecules are used, then their membrane permeability is improved, but their solubility in bodily fluids deteriorates due to high octanol-water partition coefficient
Solution Approach 1:
The patent changes the chemical parameter of the bioactive molecule by converting it into an anionic form through acid/base chemistry. This parameter change (from neutral to charged species) fundamentally alters the octanol-water partition coefficient, enabling the molecule to achieve both membrane permeability and solubility in bodily fluids simultaneously.
2Force
If the octanol-water partition coefficient is greater than 5, then membrane permeability is improved, but bioavailability is limited due to poor solubility
Solution Approach 1:
The invention modifies the molecular parameter by deprotonating the bioactive molecule to form an anion. This parameter change results in a new species with improved aqueous solubility while maintaining the ability to cross membranes, thereby resolving the bioavailability limitation.
Solution Approach 2:
The patent employs an intermediary approach by using a base compound that facilitates the conversion of the bioactive molecule into its anionic form. This intermediary mechanism enables the molecule to temporarily exist in a charged state that improves solubility while maintaining membrane permeability through the conjugate acid-base pair 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 anionic forms of bioactive agents enhance bioavailability by improving solubility in bodily fluids, effectively addressing the limitations imposed by the Rule of Five.
Implementation Method 1
Many classes of hydrophobic bioactive molecules can be converted into anions that display improved octanol-water partition coefficients using simple acid/base chemistry
Implementation Method 2
Such anions convert back into their parent bioactive molecules upon administration to a subject
Data Source
AI summary
This patent document describes excipients that allow certain bioactive agents that exist as hydrophobic molecules to be reformulated as anions that display improved hydrophilicity, which can improve the bioavailability and pharmacokinetics of broad classes of pharmaceuticals.