Acetone Solvate of Ivabradine Hydrochloride for Polymorph Purity
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Solution Overview
Problem
The existing processes for producing polymorphic forms of ivabradine hydrochloride, such as delta and delta-d, involve residual ICH class 2 solvents like acetonitrile, which are not optimal due to their harmful nature and limited industrial scalability.
Innovation Solution
A novel crystalline acetone solvate of ivabradine hydrochloride is developed, allowing for the preparation of polymorphic forms delta and delta-d with reduced acetonitrile content through a process involving acetone as the solvent, using controlled temperature and humidity conditions to achieve high-purity products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If crystallization is carried out in acetonitrile to obtain polymorphic forms delta or delta-d, then the desired polymorphic forms are produced, but residual ICH class 2 solvent remains in the product which is harmful and limits industrial scalability
Solution Approach 1:
The harmful acetonitrile solvent is extracted and replaced with acetone as the crystallization medium. The patent describes a process where ivabradine hydrochloride is crystallized from acetone solution, and the resulting acetone solvate is then treated to remove acetone and obtain the desired polymorphic forms, thereby eliminating residual ICH class 2 solvents from the final product.
Solution Approach 2:
The patent changes the solvent parameter from acetonitrile to acetone in the crystallization process. This parameter change allows obtaining the same polymorphic forms (delta and delta-d) without incorporating harmful residual solvents, as acetone is ICH class 3 solvent with higher safety margins and can be more effectively removed.
2Productivity
If conventional crystallization processes are used to produce polymorphic forms, then production can be maintained, but energy consumption and solvent usage are excessive for industrial-scale production
Solution Approach 1:
The patent employs a continuous crystallization process using acetone as solvent, where the acetone solvate formed during crystallization is directly processed without intermediate isolation steps. The acetone is removed in a continuous drying process, and the desired polymorphic forms are obtained in a single continuous operation, reducing energy consumption compared to batch processes with multiple heating and cooling cycles.
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 process effectively reduces the energy consumption and solvent usage, enabling the production of high-purity polymorphic forms of ivabradine hydrochloride with minimal residual solvent content, making it suitable for industrial-scale production and extended storage stability.
Implementation Method 1
a novel crystalline solvate of ivabradine hydrochloride and a process of its preparation
Implementation Method 2
subjecting the crystalline solvate to drying conditions or to an atmosphere having a relative humidity in a range of from up to 50%
Data Source
AI summary
The present invention relates to a novel solvate of ivabradine hydrochloride, a process of its preparation and its use for the preparation of specific polymorphic forms of ivabradine hydrochloride.