ABSD Lysine Salt Crystalline Phase Hygroscopy
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Solution Overview
Problem
The existing forms of 3S,3S' 4,4'-disulfanediylbis(3-aminobutane 1-sulfonic acid) (ABSD) are highly hygroscopic, lack thermal stability, and have variable hydration forms that complicate pharmaceutical formulations, making them unsuitable for reliable drug development due to sensitivity to moisture and humidity.
Innovation Solution
A new anhydrous crystalline phase of ABSD is formed by contacting it with L-lysine in a 1:2 stoichiometry, which enhances thermal stability, solubility, and reduces hygroscopy, offering a more stable and effective form for pharmaceutical applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If ABSD is stored as zwitterionic form under ambient conditions, then it forms stable hydrate phases, but it exhibits high hygroscopy and poor thermal stability
Solution Approach 1:
The patent changes the chemical composition parameters by forming a salt complex with lysine, transforming ABSD from zwitterionic form to a stable salt form. This parameter change resolves the contradiction by maintaining composition stability while eliminating the harmful effects of hygroscopy and thermal instability associated with hydrate phases
Solution Approach 2:
The patent creates a composite material system by combining ABSD with lysine in a 1:2 molar ratio. This composite salt form integrates the properties of both components, achieving both stable composition and reduced hygroscopy while improving thermal stability compared to the pure zwitterionic form
2Temperature
If ABSD zwitterion is dehydrated to improve thermal stability, then partial dehydration occurs below 30°C, but it causes swelling effect that jeopardizes tablet manufacturing
Solution Approach 1:
The patent changes the physical and chemical parameters of ABSD by converting it to a lysine salt form. This transformation fundamentally alters the thermal behavior, eliminating the swelling effect during dehydration while maintaining thermal stability, thus resolving the contradiction between temperature stability and shape integrity
3Ease of operation
If ABSD is used in highly hygroscopic form, then it is easy to handle initially, but it shows sensitivity to moisture and humidity complicating pharmaceutical formulations
Solution Approach 1:
The patent changes the hygroscopicity parameter by forming a stable salt with lysine. The new salt form maintains good handling properties while dramatically reducing sensitivity to moisture and humidity, thereby improving formulation reliability without sacrificing ease of operation
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 phase of ABSD with L-lysine exhibits improved thermal stability up to 180°C, higher aqueous solubility, and lower hygroscopy compared to the zwitterionic form, making it a superior alternative for pharmaceutical use, particularly in treating hypertension and related diseases.
Implementation Method 1
contacting ABSD with L-lysine, in particular in a 1:2 stoichiometry (ABSD:L-lysine)
Data Source
Figure 1
Figure 2a~2d
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AI summary
The present invention relates to a new crystalline phase of (3S,3S') 4,4'-disulfanediylbis(3-aminobutane 1-sulfonic acid) (ABSD) with L-lysine and its use, particularly in the pharmaceutical industry, and to processes for preparation thereof. The invention is also directed to pharmaceutical compositions containing at least one crystalline phase of (3S,3S') 4,4'-disulfanediylbis(3-aminobutane 1-sulfonic acid) (ABSD) with L-lysine and to the therapeutic or prophylactic use of such crystalline phase and compositions comprising the same.