Icotinib Polymorphs Enhance Solubility and Stability
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Solution Overview
Problem
Current EGFR tyrosine kinase inhibitors, such as Icotinib, face challenges in solubility and stability, limiting their bioavailability and effectiveness in cancer treatment, and there is a need for new polymorphic forms that can enhance these characteristics.
Innovation Solution
Development of polymorphic forms of Icotinib (Forms I, II, III, and IV) with specific X-ray powder diffraction patterns and melting points, prepared through methods involving solvents and temperature control, which exhibit improved solubility and stability, and methods for their production, including reactions with bases in specific media.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional Icotinib is used, then the drug can be administered for cancer treatment, but its solubility and stability are poor, limiting bioavailability and effectiveness
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple polymorphic forms (Forms I, II, III, and IV) of Icotinib, each with distinct crystal structures and physical properties. By changing the crystalline state parameter, the invention achieves different solubility and stability profiles, allowing selection of the most appropriate form for specific therapeutic applications while improving overall bioavailability and effectiveness
Solution Approach 2:
The patent creates composite crystalline structures through polymorphism, where the same chemical compound (Icotinib) is organized into different spatial arrangements. These composite crystal forms exhibit enhanced properties compared to the conventional form, particularly in solubility and stability, thereby improving drug performance without altering the chemical structure
2Productivity
If conventional Icotinib is used, then the drug structure is simple and well-defined, but its bioavailability and treatment effectiveness are limited due to poor solubility and stability
Solution Approach 1:
By changing the physical state parameter from conventional crystalline form to specific polymorphic forms (I, II, III, IV), the invention significantly improves bioavailability and treatment effectiveness. The distinct crystal structures of each polymorph provide different dissolution rates and bioavailability profiles, enabling optimized therapeutic outcomes
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 polymorphic forms of Icotinib demonstrate enhanced bioavailability and chemical stability, making them more effective for cancer treatment and other related diseases, with specific pharmaceutical compositions and administration methods for improved clinical applications.
Implementation Method 1
Many pharmaceutically active organic compounds can crystallize in more than one type of three-dimensional crystal structure. That is, the compounds may crystallize in different crystalline forms. This phenomenon (identical chemical structure but different crystalline structure) is referred to as polymorphism
Implementation Method 2
Polymorph Form I and its X-ray powder diffraction pattern having characteristic peaks at diffraction angles 2θ of approximately 7.6°, 14.7°, 20.9°, 23.1° and 27.5°±0.2°
Data Source
Figure 1
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AI summary
Provided are polymorphic forms of the compound of Formula I, preparation thereof and pharmaceutical compositions, and use of a polymorph above in the treatment of a disease, a disorder or a condition, or in the manufacturing of a medicament for the treatment of a disease, a disorder or a condition.