Complexing Agent Salts for Solubility Without Excess Ions
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Solution Overview
Problem
Pharmaceutical compounds with basic nitrogen atoms face challenges in formulation due to properties like limited solubility, hydrophobicity, and the presence of inherently ionic functional groups, which complicates their use as pharmaceutical agents, particularly in subcutaneous, sublingual, and intranasal administrations.
Innovation Solution
Formulations utilizing complexing agents, such as cyclodextrins with acidic functional groups, are used to create salts with pharmaceutical compounds, eliminating excess ions and enhancing solubility, stability, and bioavailability by forming salts directly between the compound and the complexing agent in its free acid form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional complexing agents (sodium or alkali metal salts) are used to enhance solubility, then solubility is improved, but excess ions are added to the formulation
Solution Approach 1:
The patent extracts and eliminates the harmful excess ions (sodium or alkali metal salts) from the traditional complexing agent formulations. By using the free acid form of the complexing agent instead of its salt form, the formulation achieves solubility enhancement without introducing unwanted ions that could cause adverse effects.
Solution Approach 2:
The patent changes the chemical form of the complexing agent from its salt form (containing excess ions) to its free acid form. This parameter change in the chemical composition allows the complexing agent to maintain its ability to enhance solubility while eliminating the harmful excess ions from the formulation.
2Reliability
If pharmaceutical compounds with basic nitrogen atoms are used, then therapeutic activity is achieved, but formulation difficulty increases due to limited solubility and hydrophobicity
Solution Approach 1:
The patent introduces a complexing agent as an intermediary substance that mediates between the hydrophobic pharmaceutical compound and the aqueous formulation environment. The complexing agent forms a complex with the pharmaceutical compound, enhancing its solubility and facilitating formulation while preserving the compound's therapeutic activity.
Solution Approach 2:
The patent changes the physical and chemical parameters of the pharmaceutical compound by forming a complex with the complexing agent. This complex formation alters the solubility, hydrophobicity, and other formulation-relevant parameters of the compound, making it easier to formulate while maintaining therapeutic efficacy.
3Quantity of substance
If salts are formed with complexing agents to enhance solubility, then solubility and bioavailability are improved, but osmolality increases
Solution Approach 1:
The patent extracts and eliminates the source of excess osmolality by avoiding the use of alkali metal salts in the complexing agent formulation. By using the free acid form instead of salt forms, the formulation achieves enhanced solubility and bioavailability without the osmolality increase that would result from adding sodium or other alkali metal salts.
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 resulting salts enhance solubility and stability, reduce osmolality, and increase bioavailability, particularly for sublingual and intranasal delivery, allowing for long-term storage as powders and easy redissolution at the point of use.
Implementation Method 1
the resulting salts have multiple molecules of protonated pharmaceutical compounds ionically associated with a single complexing agent
Implementation Method 2
create salts with pharmaceutical compounds having basic nitrogen atoms
Implementation Method 3
eliminating the presence of substantial excess ions
Data Source
AI summary
Provided herein are pharmaceutical formulations and pharmaceutical compound salts which utilize complexing agents as counterions. Such formulations and salts are useful for treating a variety of disease and disorders.