Complexing Agent Salt Formulations With Lower Osmolality
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Solution Overview
Problem
Pharmaceutical compounds with basic nitrogen atoms face challenges in formulation due to properties like basic amines, limited solubility, and hydrophobicity, which hinder widespread use, particularly in subcutaneous, sublingual, and intranasal administrations.
Innovation Solution
Formulations using complexing agents like cyclodextrins with acidic functional groups to create salts with pharmaceutical compounds, eliminating excess ions and enhancing solubility, stability, and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If traditional salts of complexing agents (e.g., sodium salts) are used to enhance solubility and stability, then solubility and stability are improved, but excess ions are introduced increasing osmolality
Solution Approach 1:
The patent extracts and removes the unwanted excess ion component (sodium or other alkali metal ions) from the complexing agent formulation. By using the free acid form of the complexing agent instead of its sodium salt, the formulation eliminates the source of excess ions while maintaining the beneficial complexing functionality, thus resolving the contradiction between stability enhancement and excess ion content.
Solution Approach 2:
The patent changes the chemical form of the complexing agent from a salt form (sodium salt) to a free acid form. This parameter change in the chemical state allows the complexing agent to maintain its ability to enhance formulation stability while avoiding the introduction of excess ions, thereby simultaneously improving stability and reducing ion quantity.
2Quantity of substance
If complexing agents with acidic functional groups are used to create salts with pharmaceutical compounds, then solubility and bioavailability are enhanced, but formulation complexity increases
Solution Approach 1:
The free acid form of the complexing agent serves multiple functions simultaneously: it acts as a counterion to form salts with basic nitrogen-containing pharmaceutical compounds, enhances solubility, improves stability, and reduces osmolality by avoiding excess ions. This multi-functionality simplifies the overall formulation approach while achieving multiple desirable outcomes, thus resolving the contradiction between enhanced solubility and formulation complexity.
3Reliability
If pharmaceutical compounds with basic nitrogen atoms are used, then therapeutic efficacy is achieved, but solubility and bioavailability are limited
Solution Approach 1:
The free acid form of the complexing agent acts as an intermediary that bridges the pharmaceutical compound with basic nitrogen atoms and the formulation medium. By forming a salt complex, it facilitates improved solubility and bioavailability while preserving the therapeutic efficacy of the original pharmaceutical compound, thus resolving the contradiction between efficacy and solubility.
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 formulations enhance solubility and stability, reduce osmolality, and increase bioavailability, particularly for sublingual and intranasal delivery, allowing for long-term storage and easy redissolution at the point of use.
Implementation Method 1
the formulations and salts provided herein utilize complexing agents (e.g. cyclodextrins) with a plurality of acidic functional groups in their free acid form to create salts with pharmaceutical compounds having basic nitrogen atoms
Implementation Method 2
the resulting salts have multiple molecules of protonated pharmaceutical compounds ionically associated with a single complexing agent... Such an approach can be used with any pharmaceutical compound... to form a salt with such a complexing agent which can provide numerous advantages in a variety of formulations... the formulations and salts provided herein utilize complexing agents bearing deprotonated acidic functional groups as counterions... While SBEBCD and other similar such complexing agents having anionic functionalities can be used in numerous contexts to enhance solubility and stability of many formulations... eliminating the presence of substantial excess ions
Implementation Method 3
enhancing solubility, stability, and bioavailability... the complexing agent is present in an amount of about 10 mg/mL to about 600 mg/mL... the pharmaceutical composition has lower osmolality than a composition comprising a salt of the pharmaceutical compound and a salt of the complexing agent
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.