Elacestrant Form CSII Crystallization for Solubility and Flowability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing crystalline forms of Elacestrant dihydrochloride, such as Form 1B, suffer from issues like low solubility, poor flowability, compressibility, and adhesiveness, leading to uneven drug distribution, manufacturing challenges, and potential toxicity due to impurities, which affect drug efficacy and safety.
Innovation Solution
Development of a novel crystalline form, Form CSII, with improved solubility, flowability, compressibility, and stability, characterized by specific X-ray diffraction peaks, prepared through a process involving stirring in chloroform and drying, which enhances purification and maintains uniform particle size distribution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing crystalline forms (Form 1B) are used, then manufacturing process is simple, but solubility is low and flowability is poor
Solution Approach 1:
The patent applies parameter changes by modifying the crystallization conditions (solvent system, temperature, pH) to transform Compound I dihydrochloride from existing crystalline forms with poor solubility to a new crystalline form (Form CSII) with significantly improved solubility and flowability characteristics
2Ease of manufacture
If existing crystalline forms (Form 1B) are used, then manufacturing process is simple, but flowability and compressibility are poor
Solution Approach 1:
The patent uses parameter changes in the crystallization process (adjusting solvent composition, temperature, and other physical parameters) to obtain a new crystalline form with improved flowability and compressibility, enabling better manufacturing performance
3Productivity
If existing crystalline forms are used, then production can proceed, but uneven drug distribution occurs due to poor flowability
Solution Approach 1:
The patent applies parameter changes to the crystallization process to produce a new crystalline form with uniform particle size distribution and excellent flowability, ensuring homogeneous drug distribution in formulations while maintaining production efficiency
4Productivity
If existing crystalline forms are used, then manufacturing can proceed, but impurities remain due to poor purification ability
Solution Approach 1:
The patent uses parameter changes in the crystallization process (solvent system, temperature, pH control) to enhance the purification ability of the new crystalline form, achieving better impurity rejection while maintaining manufacturing efficiency
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
Form CSII exhibits twice the solubility in FeSSIF, higher purity, better flowability, and compressibility, reducing manufacturing issues and ensuring consistent drug quality and safety by minimizing agglomeration and impurities, thus improving bioavailability and reducing side effects.
Implementation Method 1
Adding Compound I dihydrochloride into chloroform, stirring, separating and drying to obtain Form CSII
Implementation Method 2
Adding Compound I dihydrochloride into chloroform, stirring, separating and drying to obtain Form CSII
Implementation Method 3
The X-ray powder diffraction pattern of Form CSII comprises characteristic peaks at 2theta values of 10.3°±0.2°, 12.1°±0.2° and 15.4°±0.2° using CuKα radiation
Data Source
AI summary
Provided are novel crystalline forms of Elacestrant (Referred to as “Compound I”) and preparation methods thereof, pharmaceutical compositions containing the crystalline form, and uses of the crystalline form for preparing estrogen receptor depressant drugs and drugs for treating breast cancer with ER+, HER2−, ESR1 mutations.