Polycyclic ALK Inhibitor Crystal Forms for Solubility Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing crystal forms of the anaplastic lymphoma kinase inhibitor compound of formula (1) do not adequately address solubility, stability, and bioavailability issues, which are critical for effective drug development and formulation.
Innovation Solution
Development of specific crystal forms (A, B, X, and 4) characterized by unique X-ray powder diffraction patterns and thermal analysis profiles, along with a controlled preparation method involving solvent selection, temperature adjustments, and gradient cooling to produce stable crystal forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If existing crystal forms of the compound are used, then the drug can be manufactured, but solubility and bioavailability are insufficient
Solution Approach 1:
The patent applies parameter changes by developing multiple crystal forms (Form A, Form B, Form C) of the compound with different crystal structures. Each crystal form has distinct X-ray diffraction patterns and differential scanning calorimetry profiles, representing different physical parameter configurations. These structural parameter changes directly improve solubility and bioavailability while maintaining chemical stability, resolving the contradiction between stability and bioavailability.
2Reliability
If multiple crystal forms are developed, then solubility and bioavailability improve, but the complexity of drug development increases
Solution Approach 1:
The patent applies local quality by providing detailed, localized characterization methods for each crystal form. Each form (A, B, C) is characterized by specific local features including distinct X-ray diffraction peak positions, differential scanning calorimetry transition temperatures, and solubility profiles in specific pH conditions. This localized characterization approach manages complexity by providing clear, form-specific identification criteria rather than requiring comprehensive analysis of all possible properties.
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 crystal forms exhibit enhanced solubility, stability, and bioavailability, improving the quality and efficacy of the drug for treating ALK-mediated diseases.
Implementation Method 1
an X-ray powder diffraction pattern comprising characteristic peaks at 11.9±0.2°, 14.0±0.2°, 15.2±0.2°, 17.2±0.2°, 17.5±0.2°, and 21.5±0.2° expressed as 2θ angles using Cu-Kα radiation
Implementation Method 2
a differential scanning calorimetry analysis diagram comprising an endothermic peak in the range of about 190°C to 205°C
Data Source
AI summary
The present invention relates to a crystal form of a polycyclic anaplastic lymphoma kinase inhibitor and a preparation method therefor, a pharmaceutical composition comprising the crystal form, and use of the crystal form or the pharmaceutical composition. Specifically, the present invention relates to a crystal form of a compound, i.e., 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(7-methyl-8-(piperidin-4-yl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)pyrimidine-2,4-diamine, that is represented by formula (1) and serves as an anaplastic lymphoma kinase inhibitor, a preparation method therefor, a pharmaceutical composition comprising the crystal form, and the use of the crystal form or the pharmaceutical composition in a medication for preventing and/or treating an anaplastic lymphoma kinase-mediated cancer or a non-cancer related disease.