Solvent Vapour Crystallization of APIs in Rotary Cone Dryers
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Solution Overview
Problem
There is a need for scalable, industrially applicable solid-state methods for the preparation of pharmaceutical salts and multiple-component crystalline forms, such as cocrystals, that reduce environmental impact, solvent use, and equipment costs while maintaining regulatory acceptability.
Innovation Solution
A process involving the mixing of active pharmaceutical ingredients with pharmaceutically acceptable entities in the presence of solvent vapour, using standard production equipment like rotary cone dryers, to form crystalline lattices without liquid solvent, employing agitator devices and solvent vapour delivery and evacuation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If liquid solvent-based methods are used to prepare crystalline forms, then crystalline forms can be formed, but environmental impact increases and solvent waste is generated
Solution Approach 1:
The patent extracts and eliminates liquid solvent from the crystalline form preparation process by using solvent vapour instead. The method involves mixing solid API with coformer/salt in a vessel while solvent vapour is introduced through a gas inlet, forming crystalline forms without requiring liquid solvent, thereby eliminating solvent waste and reducing environmental impact
Solution Approach 2:
The patent changes the physical state parameter of the solvent from liquid to vapour phase. By introducing solvent vapour instead of liquid solvent, the process maintains the ability to form crystalline forms while eliminating the harmful effects of liquid solvent waste and reducing environmental impact
2Loss of substance
If liquid solvent is used in crystalline form preparation, then crystalline forms can be formed, but solvent waste and disposal costs increase
Solution Approach 1:
The patent removes liquid solvent from the process entirely by using solvent vapour. The crystalline forms are formed by direct contact with vapour phase solvent, eliminating the need for liquid solvent handling, recovery, and disposal operations, thereby eliminating solvent waste
Solution Approach 2:
The patent employs a disposable or recyclable vessel system where solvent vapour is introduced and then evacuated. The solvent is not retained in the product but is instead removed through evacuation, eliminating the need for expensive solvent recovery and disposal systems
3Device complexity
If standard production equipment is used, then equipment costs are reduced, but scalability and industrial applicability may be limited
Solution Approach 1:
The patent designs a versatile vessel system that can function as both a mixing device and a crystallization reactor. The same vessel used for initial mixing of solids can subsequently receive solvent vapour, mix, and facilitate crystalline form formation, eliminating the need for separate specialized equipment and enabling scalability
Solution Approach 2:
The patent introduces solvent vapour as an intermediary medium that facilitates crystalline form formation without requiring liquid solvent. The vapour phase acts as a transport medium for the crystalline form precursors, enabling the process to be conducted in standard production equipment while maintaining scalability
4Object-affected harmful factors
If solvent vapour method is used, then environmental impact and solvent waste are reduced, but residual solvent levels must be controlled to meet regulatory standards
Solution Approach 1:
The patent incorporates a vapour pressure monitoring system that provides feedback on residual solvent levels in the vessel. This allows real-time control of the solvent vapour introduction and evacuation process to ensure residual solvent levels remain below regulatory thresholds while maintaining effective crystalline form formation
Solution Approach 2:
The patent replaces liquid solvent-based mechanical mixing and handling systems with a vapour-phase process. The solvent vapour is introduced, allows contact time for crystalline form formation, and then is evacuated, eliminating the need for liquid solvent removal operations and ensuring consistent control over residual solvent levels
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 reduces environmental impact, costs, and solvent waste, while ensuring low residual solvent levels, meeting regulatory standards and enabling efficient production of crystalline forms like cocrystals and salts in standard pharmaceutical equipment.
Implementation Method 1
mixing, in the presence of solvent vapour, of the active pharmaceutical ingredient in solid form and the entity
Implementation Method 2
crystalline solids exhibit a regular and repeating packing array of a structural unit (i.e. unit cell)
Data Source
AI summary
The present invention provides solvent-limited processes for the preparation of an existing crystalline solid form of an active pharmaceutical ingredient comprising mixing, in the presence of solvent vapour, of a solid active pharmaceutical ingredient and a pharmaceutically acceptable entity that is either a high-boiling liquid or a solid. Also provided is the use of a standard rotary apparatus, such as a rotary cone dryer, for application of the processes herein.