Vortioxetine Hydrobromide Propylene Glycol Solvate Form AC1
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Solution Overview
Problem
Current processes for producing vortioxetine and its pharmaceutically acceptable salts are hindered by the use of hazardous and costly reagents, as well as extensive protection and deprotection steps, necessitating a simpler, cost-effective, and industrially viable method for improving stability, purity, flowability, solubility, and bioavailability.
Innovation Solution
A novel crystalline polymorphic form of vortioxetine hydrobromide propylene glycol solvate, designated as form AC1, is developed through a process involving the reaction of 1-chloro-2-nitrobenzene with piperazine, followed by subsequent steps to obtain vortioxetine free base, which is then converted into vortioxetine hydrobromide, and subsequently combined with propylene glycol to form the solvate, characterized by specific X-ray powder diffraction patterns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional processes are used for producing vortioxetine, then the product can be obtained, but the process involves hazardous and costly reagents and extensive protection and deprotection steps
Solution Approach 1:
The invention extracts and eliminates the hazardous and costly reagents from the synthesis pathway by employing alternative reagents and reaction conditions that achieve the same transformation without requiring protective group chemistry, thereby simplifying the manufacturing process
Solution Approach 2:
The patent employs inexpensive, readily available reagents and catalysts that can be easily disposed of or recycled, replacing expensive and hazardous materials, making the process more economically viable and environmentally friendly
2Productivity
If conventional processes are used for producing vortioxetine, then the product can be obtained, but extensive protection and deprotection steps are required
Solution Approach 1:
The invention removes the unnecessary protection and deprotection steps from the synthesis pathway by designing a route that inherently avoids sensitive functional groups requiring protection, thereby reducing process complexity and improving productivity
Solution Approach 2:
The patent employs continuous flow chemistry or one-pot multi-step reactions that eliminate intermediate isolation and protection/deprotection cycles, maintaining continuous productive action throughout the synthesis process
3Reliability
If new polymorphic forms are developed, then pharmaceutical properties such as stability and solubility are improved, but the manufacturing process becomes more complex
Solution Approach 1:
The patent achieves improved storage stability by controlling crystallization parameters such as temperature, solvent composition, and cooling rate during the formation of the novel polymorphic form, without requiring complex post-processing steps
Solution Approach 2:
The invention develops a solvate form containing propylene glycol molecules within the crystal lattice, creating a composite structure that inherently provides improved stability and solubility properties while maintaining a relatively simple manufacturing process
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 new crystalline form of vortioxetine hydrobromide propylene glycol solvate exhibits enhanced chemical purity, stability, flowability, and solubility, offering improved pharmaceutical properties such as storage stability and reduced hygroscopicity.
Implementation Method 1
a novel crystalline polymorphic form of vortioxetine hydrobromide propylene glycol solvate, designated as form AC1
Implementation Method 2
vortioxetine hydrobromide propylene glycol solvate
Data Source
AI summary
Processes are disclosed for making vortioxetine and pharmaceutically acceptable salts thereof. A propylene glycol solvate of vortioxetine hydrobromide is disclosed. A novel crystalline form of vortioxetine hydrobromide propylene glycol solvate, designated form AC1, is disclosed along with a method for making same. Form AC1 may be characterized by an x-ray powder diffraction pattern with peaks at about 19.64, 22.85, 25.51, 29.57, 30.18±0.2 degrees 2-theta.