Stable TETA Tetrahydrochloride Crystal Form for Room-Temperature Storage
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Solution Overview
Problem
Existing forms of triethylenetetramine tetrachloride (TETA·4HCl) are unstable at room temperature and sensitive to humidity, making them challenging to formulate into stable oral treatments for conditions like Wilson's disease.
Innovation Solution
A new crystalline form of TETA·4HCl, known as Form B, is produced by carefully controlling the temperature and rate of crystallization, typically at 20°C or below, ensuring improved stability and handling properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional crystallization methods are used to produce TETA·4HCl, then the compound can be obtained, but it forms unstable crystalline forms (Form A) that decompose at room temperature and require special storage conditions
Solution Approach 1:
The patent applies parameter changes by carefully controlling crystallization temperature (0-20°C) and rate to transform the unstable Form A into the stable Form B crystalline structure. This parameter optimization resolves the contradiction by producing a form that is both reliable in stability and easy to store under ambient conditions.
Solution Approach 2:
The patent utilizes phase transitions during crystallization to achieve form transformation. By controlling the phase change process under specific temperature and rate conditions, the unstable Form A transitions to the stable Form B phase, eliminating the need for special storage conditions while maintaining reliability.
2Ease of operation
If TETA·4HCl is stored at room temperature, then ease of operation is improved, but the compound deteriorates due to instability and humidity sensitivity
Solution Approach 1:
The patent changes the crystalline form parameter from Form A to Form B through controlled crystallization. This parameter change enables the compound to maintain stability at room temperature, simultaneously achieving ease of operation and reliability without requiring special storage conditions.
Solution Approach 2:
The patent eliminates the need for expensive and complex refrigeration storage systems by producing a crystalline form that is inherently stable at ambient conditions. This resolves the contradiction by making both storage and long-term stability achievable under simple, inexpensive conditions.
3Ease of operation
If high humidity is present, then ease of operation is improved, but the compound stability deteriorates due to polymorphic transformation
Solution Approach 1:
The patent changes the crystalline form parameter to Form B, which has superior humidity resistance. This parameter change allows the compound to maintain compositional stability even in high humidity environments, resolving the contradiction between ease of operation and polymorphic stability.
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
Form B exhibits enhanced stability at room temperature and in humid environments, allowing for the development of stable oral formulations for treating Wilson's disease without the need for special storage conditions.
Implementation Method 1
a new crystalline form of TETA·4HCl can be produced. This new form has good handling properties and also good stability and shelf life characteristics
Data Source
AI summary
The present invention describes a new crystalline form of triethylenetetramine tetrachloride which has improved room temperature stability over known forms and over the dichloride salt. The new crystalline form is characterised by having peaks in an XRPD spectrum at 22.9, 25.4, 25.8, 26.6, 34.6 and 35.3±0.1° 2θ and Raman shifts 943, 1173, 1527 and 1612±5 cm−1. The crystalline form of triethylenetetramine tetrachloride is useful in the treatment of Wilson's disease.