Aqueous Gel Formulations for Immune Response Modifiers
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Solution Overview
Problem
The low intrinsic aqueous solubility of immune response modifier (IRM) compounds hinders the formation of effective aqueous gel formulations, leading to issues like irritation, washaway, degradation, and poor permeation when applied topically, limiting their therapeutic benefit.
Innovation Solution
Aqueous gel formulations are developed using a combination of water, a pharmaceutically acceptable acid, a water-miscible cosolvent, and a thickener system including negatively charged thickeners, which maintains the IRM compound in a therapeutically effective form with desired viscosity, reducing systemic exposure and enhancing stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a cosolvent is used to improve aqueous solubility of IRM compounds, then solubility is improved, but formulation stability deteriorates due to separation and precipitation
Solution Approach 1:
The patent introduces a specifically designed thickener system as an intermediary substance that mediates between the IRM compound and the aqueous environment. This thickener system enables the formulation to achieve desired viscosity and stability without requiring high concentrations of cosolvents, thereby preventing separation and precipitation while maintaining adequate solubility.
Solution Approach 2:
The patent changes the physical parameters of the formulation by incorporating a thickener system that modifies viscosity and rheological properties. This parameter change allows the formulation to maintain IRM compounds in solution at lower cosolvent concentrations, improving both solubility and stability simultaneously.
2Duration of action of moving object
If negatively charged thickeners are used to increase viscosity, then residence time is improved, but systemic exposure increases
Solution Approach 1:
The patent applies local quality by using negatively charged thickeners that specifically interact with the positively charged IRM compounds to enhance local retention at the application site. This localized interaction increases residence time without causing widespread systemic absorption, as the thickener-IRM complex remains confined to the topical application area.
3Reliability
If IRM compounds are applied topically to treat localized conditions, then therapeutic benefit is improved, but formulation washaway occurs
Solution Approach 1:
The patent creates a composite formulation system combining IRM compounds, cosolvents, and thickener systems into a unified gel structure. This composite material enhances adhesion to the application site while maintaining the therapeutic properties of the IRM compounds, preventing washaway without compromising therapeutic benefit.
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 provide increased residence time on dermal and mucosal tissues, reduce systemic cytokine levels, and ensure physical stability, allowing for effective topical delivery of IRM compounds to treat conditions like cervical dysplasia and viral infections.
Implementation Method 1
the low intrinsic aqueous solubility of the free base (typically less than 500 μg/mL at 25° C.)
Implementation Method 2
a thickener system including a negatively charged thickener; wherein the aqueous gel has a viscosity of at least 1000 cps at 25° C.
Implementation Method 3
the use of negatively charged thickeners in the aqueous gels of the present invention reduces systemic exposure to the drug and hence reduces systemic levels of cytokines
Data Source
AI summary
Aqueous gel formulations, including an immune response modifier (IRM), such as those chosen from imidazoquinoline amines, tetrahydroimidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, oxazoloquinoline amines, thiazoloquinoline amines, oxazolopyridine amines, thiazolopyridine amines, oxazolonaphthyridine amines, thiazolonaphthyridine amines, pyrazolopyridine amines, pyrazoloquinoline amines, tetrahydropyrazoloquinoline amines, pyrazolonaphthyridine amines, tetrahydropyrazolonaphthyridine amines, and 1H-imidazo dimers fused to pyridine amines, quinoline amines, tetrahydroquinoline amines, naphthyridine amines, or tetrahydronaphthyridine amines, are provided. Methods of use and kits are also provided.