Glucocorticoid Receptor Modulator Lipid Formulation for Solubility Stability
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Solution Overview
Problem
Existing compositions of glucocorticoid receptor modulators, such as Compound I, face challenges with solubility and stability, making them unsuitable for pharmaceutical use, and there is a need for improved treatment options for conditions like amyotrophic lateral sclerosis (ALS) and Alzheimer's disease.
Innovation Solution
Formulations comprising Compound I, a cosolvent, and a surfactant in specific weight percentages, forming Type IV lipid formulations that enhance solubility and stability, suitable for oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucocorticoid receptor modulators are used to treat diseases, then therapeutic effects are achieved, but solubility and stability problems occur making them unsuitable for pharmaceutical use
Solution Approach 1:
The patent uses self-emulsifying drug delivery systems (SEDDS) as intermediary carriers to solubilize the hydrophobic glucocorticoid receptor modulator Compound I. The SEDDS formulation includes surfactants and co-solvents that act as mediators between the drug and aqueous biological environments, enabling the insoluble compound to be delivered effectively while maintaining stability and bioavailability
Solution Approach 2:
The patent changes the physical and chemical parameters of the drug delivery system by formulating Compound I in lipid-based self-emulsifying systems with specific surfactant-to-oil ratios and co-solvent compositions. This transforms the drug from an insoluble solid into a solubilized formulation with improved pharmacokinetic properties while maintaining therapeutic efficacy
2Ease of operation
If existing compositions are used, then treatment is provided, but solubility limitations prevent effective pharmaceutical administration
Solution Approach 1:
SEDDS formulations serve as intermediaries that bridge the gap between hydrophobic drug molecules and aqueous administration routes. The surfactant-containing lipid system mediates solubilization, allowing oral or parenteral administration of Compound I at therapeutically effective concentrations
Solution Approach 2:
The patent creates composite material systems combining Compound I with lipid vehicles, surfactants, and co-solvents in specific ratios. This composite formulation approach enables the hydrophobic drug to achieve adequate solubility and stability for pharmaceutical use while maintaining its biological activity
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 improved solubility and bioavailability of Compound I, enabling effective treatment of conditions like ALS and Alzheimer's disease.
Implementation Method 1
a surfactant, in an amount of from 50 to 90% (w/w)
Implementation Method 2
a cosolvent, in an amount of from 1 to 25% (w/w)
Data Source
AI summary
The present invention provides formulations of (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone, and methods of making and using the same.