Compound 1 Salt And Cocrystal Forms For Stable IDO Drug Formulation
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Solution Overview
Problem
There is a need for new forms of (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide with desirable chemical and physical properties, as well as reliable methods for their manufacture, purification, and formulation to facilitate commercialization, particularly for use in treating diseases mediated by indoleamine 2,3-dioxygenase (IDO).
Innovation Solution
The development of salts and cocrystals of (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide, including ethane sulfonate, hydrochloride, hydrosulfate, and various hydrates and solvates, along with methods for their production and formulation, to enhance stability, processing, and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new solid forms (salts and cocrystals) of Compound 1 are developed to improve stability and bioavailability, then the therapeutic effectiveness is improved, but the device complexity and manufacturing complexity increase
Solution Approach 1:
The patent applies parameter changes by developing multiple salt forms (hydrochloride, esylate, hydrosulfate) and cocrystal forms of Compound 1 with different counterions and coformers. This changes the chemical and physical parameters of the compound to achieve desired stability, solubility, and bioavailability profiles while maintaining the core therapeutic activity against IDO-mediated diseases
Solution Approach 2:
The patent employs composite materials by creating cocrystals combining Compound 1 with various coformers (oxalate, tartrate, malate, succinate, fumarate, citrate, nicotinamide, theophylline, caffeine). These composite solid forms integrate multiple components with complementary properties to enhance overall performance characteristics including stability and bioavailability
2Reliability
If multiple solid forms are produced to enhance bioavailability and stability, then the therapeutic efficacy is improved, but the manufacturing precision and purification difficulty increase
Solution Approach 1:
The patent applies segmentation by systematically developing distinct salt forms (hydrochloride, esylate, hydrosulfate) and separate cocrystal forms with different coformers. Each form can be independently purified and characterized, allowing for targeted optimization of bioavailability and stability without requiring simultaneous purification of all forms
Solution Approach 2:
The patent uses counterions and coformers as intermediary substances that facilitate the formation of stable, pure solid forms. These intermediaries (such as HCl, oxalate, tartrate) enable controlled crystallization and purification processes, making it easier to achieve high purity and consistent bioavailability characteristics
Data Source
AI summary
The present disclosure relates to amorphous and crystalline forms of (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoro-quinolin-4-yl)cyclohexyl)propanamide and its salts/cocrystals, solvates, and/or hydrates, processes for their production, pharmaceutical compositions comprising them, and methods of treatment using them.