Crystalline Form A for Stable Bromopyrido Triazolopyrazine Drug
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing crystalline and amorphous forms of 1-(8-bromopyrido[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)-N-methylazetidin-3-amine exhibit instability, interconversion to other polymorphic forms, and unsuitable physical properties for pharmaceutical use, such as solubility and stability issues under varying humidity and temperature conditions.
Innovation Solution
Development of a novel crystalline form A, characterized by specific XRPD reflections at approximately 7.0, 22.6, and 26.3 degrees, which is thermodynamically stable up to 273°C and maintains stability under stress testing at high temperature and humidity, ensuring reliable production and storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If existing crystalline forms and amorphous forms of the compound are used, then the compound can be produced and stored, but they exhibit instability and interconversion to other polymorphic forms under varying humidity and temperature conditions
Solution Approach 1:
The patent identifies and characterizes a specific crystalline form (Form A) with distinct physical parameters including specific XRPD reflections at 2θ = 7.0, 22.6, and 26.3 degrees, melting point of 273°C, and specific solubility characteristics. This form exhibits enhanced stability compared to other polymorphic forms and amorphous forms, maintaining its structural integrity under varying humidity and temperature conditions without interconverting to other forms.
Solution Approach 2:
The patent creates a reproducible crystalline form A through a defined crystallization process that can be consistently replicated. The form is characterized by specific XRPD patterns, melting point, and solubility properties that serve as copyable criteria for identifying and producing the desired polymorphic form reliably across different batches and conditions.
2Ease of manufacture
If other crystalline forms and salts of the compound are used, then the compound can be formulated, but they exhibit interconversion upon drying or loss of water at relatively low temperature
Solution Approach 1:
The patent specifies Form A as a crystalline form of the free base with distinct physical parameters including XRPD reflections at 2θ = 7.0, 22.6, and 26.3 degrees, and a melting point of 273°C. This form is stable upon drying and does not undergo interconversion at relatively low temperatures, unlike other crystalline forms and salts that convert between hydrate and anhydrate forms or interconvert polymorphic forms under similar conditions.
3Stability of the object's composition
If crystalline forms with distinct physical properties are selected, then the compound can be optimized for pharmaceutical use, but the crystallization process must be robust and reliably produce the desired crystalline form in polymorphically pure form
Solution Approach 1:
The patent defines Form A by specific characteristic parameters including XRPD reflections at 2θ = 7.0, 22.6, and 26.3 degrees, melting point of 273°C, and specific solubility characteristics. These parameters serve as control criteria during crystallization to ensure production of polymorphically pure Form A with the desired physical properties for pharmaceutical applications.
Solution Approach 2:
The patent establishes a reproducible crystallization process that consistently produces Form A with identical characteristic properties across different batches. The XRPD pattern, melting point, and solubility characteristics serve as copyable identifiers that confirm the production of the desired polymorphic form with high purity and consistency.
Data Source
AI summary
Novel crystalline forms of 1-(8-bromopyrido[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)-N-methylazetidin-3-amine is provided along with pharmaceutical compositions comprising the same. Also disclosed is the use of the novel polymorph for the treatment of diseases, such as atopic dermatitis (AD), itch, pruritus and various forms of urticaria for example chronic idiopathic urticaria subtypes.