Plasma Kallikrein Inhibitor Solid Form Stability
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Solution Overview
Problem
Current plasma kallikrein inhibitors, such as Ecallantide, are often large proteins that can cause anaphylactic reactions and have limitations in stability and handling during pharmaceutical manufacturing, and existing small molecule inhibitors may have polar and ionizable functional groups that affect their efficacy and stability.
Innovation Solution
Development of a novel solid form (Form 1) of the compound of Formula A, characterized by specific X-ray powder diffraction peaks, which exhibits improved physico-chemical properties like reduced hygroscopicity, stability, and ease of processing, suitable for oral solid dosage forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If large protein plasma kallikrein inhibitors (such as Ecallantide) are used, then therapeutic efficacy is achieved, but anaphylactic reactions occur and manufacturing stability is compromised
Solution Approach 1:
The patent changes the molecular size parameter by transitioning from large protein inhibitors to small molecule inhibitors, thereby maintaining therapeutic efficacy while eliminating anaphylactic reactions and improving manufacturing stability
Solution Approach 2:
The patent employs small molecule inhibitors that can be easily synthesized and disposed of, replacing complex protein inhibitors that require sophisticated manufacturing and have stability issues
2Ease of manufacture
If small molecule plasma kallikrein inhibitors are used, then manufacturing stability improves, but polar and ionizable functional groups affect efficacy and stability
Solution Approach 1:
The patent modifies the chemical structure parameters of small molecule inhibitors by removing or modifying polar and ionizable functional groups, thereby maintaining manufacturing stability while preserving therapeutic efficacy
Solution Approach 2:
The patent extracts or removes problematic polar and ionizable functional groups from the small molecule inhibitor structure, eliminating their negative effects on efficacy and stability while retaining the core inhibitory activity
3Ease of manufacture
If conventional solid forms of plasma kallikrein inhibitors are used, then dosage form preparation is straightforward, but hygroscopicity and processing difficulty increase
Solution Approach 1:
The patent changes the physical state parameters by developing a novel solid form with specific crystal structure, thereby reducing hygroscopicity and improving processing ease while maintaining straightforward dosage form preparation
Data Source
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AI summary
The present inventionrelates tooral solid dosage forms comprising a plasma kallikrein inhibitor, in particular a solid form (Form 1) of the compoundof Formula A. Also provided are methods of preparing oral solid dosage forms comprising the compound of Formula A using Form 1 of the compound of Formula A.