Ubrogepant Amorphous Form Preparation via Two-Stage Vacuum Drying
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Solution Overview
Problem
Existing processes for preparing Ubrogepant result in pseudo-amorphous forms with low purity and high residual solvent levels, making them unsuitable for pharmaceutical applications.
Innovation Solution
A process involving the dissolution of Ubrogepant in a suitable solvent, followed by isolation of the pure amorphous form using techniques such as solvent removal or anti-solvent addition, to achieve a product with greater than 99% purity and minimal residual solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If Ubrogepant acetonitrile-water solvate is dried at 75°C under vacuum for one hour, then pseudo-amorphous form is obtained, but purity is low and residual solvent levels are high
Solution Approach 1:
The patent changes the drying parameters from 75°C for one hour to a two-stage process: initial drying at 75°C under vacuum for 1 hour, followed by extended drying at 40°C under vacuum for 18-24 hours. This parameter modification achieves both high purity (>99.5%) and low residual solvent content (<0.5%) in the amorphous form of Ubrogepant.
Solution Approach 2:
The patent performs preliminary characterization of the solvate structure and dissolution behavior before finalizing the drying protocol. This preliminary action allows optimization of the drying conditions to achieve complete solvate dissolution and amorphous form formation while minimizing residual solvents.
2Reliability
If amorphous form is prepared from crystalline form, then dissolution characteristics improve, but process complexity increases
Solution Approach 1:
The patent utilizes phase transition from crystalline solvate to amorphous form through controlled drying. The process involves dissolving the crystalline Ubrogepant acetonitrile-water solvate in water and then drying the solution to obtain the amorphous form, leveraging phase transition to improve dissolution characteristics while maintaining process simplicity.
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 resulting pure amorphous form of Ubrogepant exhibits high stability, low crystalline content, and meets pharmaceutical purity and residual solvent requirements, making it suitable for pharmaceutical preparations.
Implementation Method 1
Crystalline solids normally require a significant amount of energy for dissolution due to their highly organized, lattice like structures. For example, the energy required for a drug molecule to escape from a crystal is more than from an amorphous or a non-crystalline form
Implementation Method 2
The prior art describes the preparation of pseudo-amorphous form of Ubrogepant by drying of Ubrogepant acetonitrile-water solvate at 75° C. under vacuum for one hour
Data Source
AI summary
The present application relates to a pure amorphous form of Ubrogepant and its process for the preparation thereof. Ubrogepant is chemically known as (3′S)—N-((3S, 5S, 6R)-6-methyl-2-oxo-5-phenyl-1-(2, 2, 2trifluoroethyl) piperidin-3-yl)-2′-oxo-1′, 2′, 5, 7-tetrahydro spiro [cyclopenta [b] pyridine-6, 3′-pyrrolo [2, 3b] pyridine]-3-carboxamide and it is represented by the following structural formula-1.