Crystalline Salt Form for Pharmaceutical Handling Stability
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Solution Overview
Problem
The existing compound (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate is not suitable for pharmaceutical development due to its foam or oil form, which complicates handling and industrial application, lacking stability and purity.
Innovation Solution
A novel salt form, specifically (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate with multiple crystal forms (I to VIII), exhibiting improved stability, strong crystallinity, and reduced impurities, is developed, enhancing its physical properties for pharmaceutical use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the compound is used in its original form, then it shows biological activity as a muscarine M3 receptor antagonist, but it exists as foam or oil which makes it unsuitable for pharmaceutical development and difficult to handle industrially
Solution Approach 1:
The patent applies parameter changes by converting the physical state of the compound from foam or oil to crystalline solid through salt formation. This transformation maintains the biological activity while dramatically improving handling properties, solubility, and suitability for pharmaceutical formulation.
Solution Approach 2:
The patent creates composite materials by forming salts of the active compound with various acids (oxalate, citrate, tartrate, etc.). These salt forms combine the pharmacologically active base compound with counterions to produce materials with improved physical properties including crystallinity, stability, and solubility characteristics suitable for drug development.
2Reliability
If the compound is used in its original form, then it shows biological activity, but it lacks stability and has high impurity content
Solution Approach 1:
The patent uses parameter changes by altering the chemical composition through salt formation, which stabilizes the active compound. The salt forms exhibit enhanced stability and reduced impurity content compared to the original free base form, while maintaining the desired biological activity.
Solution Approach 2:
The patent introduces acid counterions as intermediaries that form stable salt complexes with the active compound. These intermediary salt structures protect the active pharmacophore while providing improved stability and purity profiles suitable for pharmaceutical applications.
3Stability of the object's composition
If a salt form is created to improve physical properties, then crystallinity and stability are enhanced, but the complexity of salt selection and characterization increases
Solution Approach 1:
The patent applies segmentation by systematically evaluating and selecting from multiple acid candidates (oxalic acid, citric acid, tartaric acid, etc.) to form distinct salt forms. Each salt is characterized independently, allowing selection of the most suitable form for specific pharmaceutical applications based on desired properties.
Solution Approach 2:
The patent utilizes parameter changes by varying the acid counterion to achieve different crystalline forms with distinct properties. This systematic approach allows optimization of solubility, stability, and other critical parameters while maintaining the active pharmacological component.
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 novel salt form provides a stable, non-hygroscopic, and high-purity crystalline solid, suitable for pharmaceutical formulations, with enhanced mechanical stability and solubility, facilitating industrial production and efficacy as a muscarine M3 receptor antagonist.
Implementation Method 1
The present invention provides an (R)-(1-methylpyrrolidine-3-yl)methyl(3'-chloro-4'-fluoro-[1,1'-biphenyl]-2-yl)carbamate oxalate and crystal forms thereof
Data Source
AI summary
The present invention relates to a novel salt of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate and a crystal form thereof. Also, the novel salt of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate and the crystal form thereof according to examples of the present invention have remarkably excellent stability, hygroscopicity and solubility.