Crystalline Cholinate Salt for Pyrazole Benzoic Acid Bioavailability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The existing form of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-4-(trifluoromethyl)-phenyl]cyclopropyl}carbonyl)amino]benzoic acid, known as the free acid, does not exhibit sufficient bioavailability at higher doses, making it unsuitable for reliable toxicological testing and pharmaceutical applications, and most tested salts are either amorphous or partially crystalline, which are difficult to handle in pharmaceutical processing.
Innovation Solution
The development of the choline salt, specifically the 2-hydroxy-N,N,N-trimethylethanaminium salt, also known as cholinate, which is crystalline, provides good bioavailability over a wide dosage range and is less hygroscopic, ensuring stability and ease of handling in pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the free acid form is used, then the compound can be synthesized and tested, but bioavailability is insufficient at higher doses
Solution Approach 1:
The patent applies parameter changes by converting the free acid into a salt form (cholinate). This chemical parameter change fundamentally alters the compound's properties, resulting in improved bioavailability and extended usable dose range for toxicological testing and pharmaceutical applications.
Solution Approach 2:
The invention creates a composite structure by forming a salt between the active compound and choline. This composite material (cholinate salt) combines the pharmacological activity of the original compound with the beneficial pharmacokinetic properties of the choline salt form, achieving both crystalline structure and improved bioavailability.
2Reliability
If most tested salts are used, then salt formation is attempted to improve properties, but they are amorphous or partially crystalline and difficult to handle
Solution Approach 1:
The patent successfully achieves a crystalline form by changing the chemical parameter of salt formation with choline. This specific parameter change (choosing choline as the counterion) results in a stable crystalline structure that is easy to handle, unlike other tested salts that remained amorphous or partially crystalline.
Data Source
AI summary
The present invention relates to the choline salt (cholinate) of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-4-(trifluoromethyl)-phenyl]cyclopropyl}carbonyl)amino]benzoic acid. In particular, the invention relates to the compound according to formula (II):or a tautomer, solvate or hydrate thereof, as well as to medical uses of the cholinate according to the invention.