Crystalline API Forms for Reproducible Polymorphic Purity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for a substantially polymorphically pure crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile that can be effectively, safely, and reproducibly used on a large scale for industrial manufacture, particularly for the treatment of dermatological conditions.
Innovation Solution
The development of crystalline forms I, II, and III of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile, characterized by specific X-ray diffraction patterns and prepared through controlled crystallization processes using solvents and anti-solvents with controlled water activity, to achieve high polymorphic purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional crystallization methods are used, then production can proceed, but polymorphic purity cannot be ensured
Solution Approach 1:
The patent applies parameter changes by precisely controlling water activity (aw) levels during crystallization to obtain specific polymorphic forms. By adjusting aw parameters and using controlled anti-solvent addition, the process achieves reproducible polymorphic purity while maintaining industrial scalability
Solution Approach 2:
The patent uses anti-solvents as intermediaries to control the crystallization process. The anti-solvent mediates between the solvent system and the compound, enabling precise control over polymorphic form formation while maintaining process simplicity and scalability
2Productivity
If large-scale industrial manufacture is pursued, then production volume increases, but reproducibility and safety decrease
Solution Approach 1:
The patent applies preliminary action by establishing detailed pre-crystallization conditions including specific water activity ranges and anti-solvent addition protocols. These preliminary controls ensure that when scaling to large production volumes, the polymorphic form remains consistent and reproducible across different manufacturing scales
Solution Approach 2:
The patent maintains reliability during scale-up by carefully controlling critical parameters such as water activity, temperature, and anti-solvent addition rate. These parameter controls ensure that the crystallization process produces consistent polymorphic forms regardless of production volume
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 crystalline forms provide efficient and reproducible pharmaceutical compositions with suitable stability, enabling effective treatment of dermatological conditions such as psoriasis and atopic dermatitis in non-human mammals.
Implementation Method 1
prepared through controlled crystallization processes using solvents and anti-solvents with controlled water activity
Implementation Method 2
controlled crystallization processes using solvents and anti-solvents with controlled water activity, to achieve high polymorphic purity
Implementation Method 3
characterized by specific X-ray diffraction patterns
Data Source
AI summary
The present disclosure provides crystalline forms of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile, pharmaceutical compositions comprising the crystalline forms, methods of using the crystalline forms, and processes for making the crystalline forms.