LA1 Salt Crystalline Forms for Dissolution and Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing formulations of leukadherin 1 (LA1) lack improved dissolution profiles, pharmacokinetic profiles, and stability profiles, limiting its efficacy in treating β2 integrin-mediated conditions.
Innovation Solution
Development of novel salts and crystalline forms of LA1, including choline and meglumine salts with specific crystalline forms such as G, O, Q, H, and T, which enhance bioavailability and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing formulations of LA1 are used, then the basic anti-inflammatory activity is maintained, but the dissolution profile, pharmacokinetic profile, and stability profile are insufficient
Solution Approach 1:
The patent changes the physical and chemical parameters of LA1 by creating multiple crystalline forms (Forms A-N) with different crystal structures, and by forming salt compounds with various bases. These parameter changes result in improved stability profiles, dissolution rates, and pharmacokinetic properties while maintaining the anti-inflammatory efficacy of the compound.
Solution Approach 2:
The patent creates composite formulations by combining LA1 with different salt-forming bases (such as choline, meglumine, and other pharmaceutically acceptable bases) to produce salt compounds. These composite materials exhibit improved stability and pharmacokinetic profiles compared to the free acid form of LA1.
2Reliability
If existing formulations of LA1 are used, then the basic anti-inflammatory activity is maintained, but the dissolution profile is insufficient
Solution Approach 1:
The patent modifies the physical parameters of LA1 by establishing multiple crystalline forms with different packing arrangements and molecular orientations. These parameter changes significantly improve the dissolution profile, allowing for faster and more complete dissolution of the compound in biological fluids, thereby enhancing bioavailability and efficacy.
3Reliability
If existing formulations of LA1 are used, then the basic anti-inflammatory activity is maintained, but the pharmacokinetic profile is insufficient
Solution Approach 1:
The patent changes the physical state and chemical form of LA1 by creating multiple crystalline forms and salt compounds. These parameter changes result in improved pharmacokinetic profiles, including enhanced absorption, extended half-life, and optimized bioavailability, thereby improving the duration of action and overall efficacy of the compound.
Data Source
AI summary
The present invention provides new salts and crystalline forms of leukadherin LA1 [(Z)-4-(5-((3-benzyl-4-oxo-2-thioxothiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid] according to Formula I. Methods for preparation of the salts and crystalline forms are also described, as well as methods for treating β2 integrin-mediated diseases and conditions using the salts and crystalline forms.