Daprodustat Crystal Form M for Solubility and Purity Balance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing crystal forms of Daprodustat exhibit poor solubility and low purity, which affects bioavailability and suitability for industrial production.
Innovation Solution
Development of new crystal forms M and K with improved solubility and purity, characterized by specific X-ray powder diffraction peaks and thermal stability, prepared through a method involving solvent treatment and crystallization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If existing crystal forms (CS1 and CS9) are used to improve purity, then purity is improved, but solubility deteriorates
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing a new crystal form (Form M) with different crystal structure parameters compared to existing forms CS1 and CS9. This new crystal form exhibits improved solubility (1.82-2.19 times higher) while maintaining high purity (99.96%), resolving the contradiction between purity improvement and solubility deterioration through fundamental changes in crystal lattice parameters and molecular arrangement.
2Manufacturing precision
If crystal forms CS1 and CS9 are used to achieve high purity, then purity is improved, but dissolution performance deteriorates
Solution Approach 1:
The patent resolves this contradiction by identifying crystal form M with fundamentally different physical parameters including improved solubility (1.82-2.19 times higher than CS1 and CS9) and corresponding dissolution performance. The new crystal form maintains manufacturing precision at 99.96% purity while achieving excellent dissolution characteristics essential for pharmaceutical formulation and bioavailability.
3Quantity of substance
If new crystal form M is developed to improve solubility, then solubility is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies preliminary action by establishing a systematic approach to crystal form screening and identification before formulation development. The new crystal form M was identified through preliminary polymorph screening using X-ray powder diffraction characterization, allowing manufacturers to select the optimal crystal form early in the development process. This preliminary characterization prevents later manufacturing complications and simplifies production by providing clear identification criteria (specific diffraction peaks at 2θ angles of 4.7±0.2°, 6.5±0.2°, and 6.8±0.2°).
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
Crystal form M shows enhanced solubility by 1.82-2.19 times, higher purity of 99.96%, and stability under various conditions, facilitating stable pharmaceutical formulations.
Implementation Method 1
an X-ray powder diffraction of the crystal form M using Cu-Kα radiation has characteristic peaks at 2θ angles of 4.7±0.2°, 6.5±0.2° and 6.8±0.2°
Implementation Method 2
an X-ray powder diffraction of the crystal form M using Cu-Kα radiation has characteristic peaks at 2θ angles of 4.7±0.2°, 6.5±0.2° and 6.8±0.2°
Implementation Method 3
a differential scanning calorimetry curve of the crystal form M has an absorption peak at 122.8±2° C.
Implementation Method 4
the crystal form M has a thermal weight loss of less than 3.2% before 100° C. in a thermo gravimetric analysis curve
Data Source
AI summary
Disclosed is crystal form M of the proline hydroxylase inhibitor daprodustat, wherein the X-ray powder diffraction thereof, expressed in 2θ angles and using Cu-Ka radiation, has characteristic peaks at 4.7±0.2°, 6.5±0.2°, and 6.8±0.2°. Disclosed are the preparation method for and the use of crystal form M. The crystal form M has good light stability, high temperature stability and high humidity stability, good solubility, and high purity.