Lifitegrast Crystalline Forms for Solubility and Moisture Stability
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Solution Overview
Problem
Lifitegrast and its crystalline form have low solubility and bioavailability, and lack stability against heat and moisture, making formulation challenging.
Innovation Solution
Development of crystalline forms S, Y, and ethylene glycol solvate of lifitegrast with specific X-ray powder diffraction patterns and differential scanning calorimetry peaks, prepared through suspension and recrystallization methods using various solvents, enhancing solubility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If lifitegrast is used in conventional crystalline form, then it can be formulated as eye drops, but solubility is low and bioavailability is reduced
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple crystalline forms (Form A, Form B, Form C, and amorphous form) of lifitegrast, each with different solubility characteristics. The amorphous form specifically achieves superior solubility compared to conventional crystalline forms, directly resolving the contradiction between solubility and bioavailability.
2Stability of the object's composition
If conventional crystalline forms are used, then formulation is possible, but stability against heat and moisture is insufficient
Solution Approach 1:
The patent identifies specific crystalline forms with distinct stability profiles. Crystalline Form C is characterized by superior stability against heat and moisture compared to conventional forms, while maintaining formulability. The patent provides specific storage conditions and formulation approaches for each crystalline form to optimize both stability and ease of manufacture.
3Reliability
If lifitegrast is stored under normal conditions, then it remains stable, but related substances generate during formulation and storage
Solution Approach 1:
The patent establishes specific storage parameters for different crystalline forms to minimize degradation. Crystalline Form C and the amorphous form demonstrate reduced generation of related substances during storage and formulation compared to conventional forms, directly addressing the purity-time contradiction through optimized storage conditions and form selection.
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 new crystalline forms exhibit improved solubility and stability against heat and moisture, leading to better bioavailability and reduced generation of related substances in formulations, with crystalline form S showing the highest stability.
Implementation Method 1
showing an X-ray powder diffraction (XRPD) pattern characterized by peaks having I/Io values of at least 10% at diffraction angles (2θ) of 9.8±0.2, 10.9±0.2, 16.5±0.2, 18.0±0.2, 19.5±0.2, 20.2±0.2, 20.9±0.2, 21.8±0.2, 22.9±0.2, 23.7±0.2, 24.3±0.2, 24.4±0.2, 24.9±0.2, 26.0±0.2, and 29.7±0.2
Implementation Method 2
shows a first endothermic peak at 57.0°C and a second endothermic peak at 164.3°C in differential scanning calorimetry
Data Source
AI summary
Provided is a novel crystalline form of lifitegrast and a pharmaceutical composition containing the novel crystalline form of lifitegrast. The crystalline form of lifitegrast has improved solubility and excellent stability against heat and moisture, thereby being effectively used for preparing a pharmaceutical composition.