Amorphous Bismuth-1,2-Ethanedithiol Synthesis via Solvent Parameter Control
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Solution Overview
Problem
There is a need for an amorphous form of bismuth-1,2-ethanedithiol (BisEDT) with improved physicochemical properties and bioavailability for effective pharmaceutical use, as previous syntheses have resulted in crystalline forms despite claims of amorphous production.
Innovation Solution
A method involving the mixing of an acidic aqueous solution containing a bismuth salt with a solvent, followed by combination with 1,2-ethanedithiol under specific conditions to form an amorphous BisEDT precipitate, which is then purified and characterized by X-ray powder diffraction and differential scanning calorimetry, resulting in a stable amorphous form with a glass transition at 101°C and specific purity levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional synthesis methods using ethanolic solvents are used to produce BisEDT, then the synthesis process is simple and well-established, but the product obtained is crystalline form which has inferior solubility and bioavailability
Solution Approach 1:
The patent applies parameter changes by modifying the solvent system from traditional ethanolic solvents to a water/organic solvent mixture system. Specifically, it uses an acidic aqueous solution containing bismuth nitrate mixed with organic solvents like acetonitrile, dichloromethane, or ethyl acetate. This parameter change in solvent composition and pH conditions enables the formation of amorphous BisEDT precipitate instead of crystalline form, thereby improving solubility and bioavailability while maintaining manufacturability through established precipitation techniques
2Reliability
If amorphous form of BisEDT is produced to improve solubility and bioavailability, then pharmaceutical efficacy is enhanced, but the synthesis process becomes more complex and requires precise control of conditions
Solution Approach 1:
The patent establishes specific parameter ranges for reliable amorphous form production: pH 1-3 acidic conditions, bismuth salt to thiol molar ratios of 1:1 to 1:5, and specific organic solvent to water ratios. These parameter specifications ensure consistent amorphous precipitate formation while maintaining pharmaceutical efficacy through improved solubility and bioavailability
Solution Approach 2:
The patent employs characterization techniques including X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) to verify the amorphous form of BisEDT. These analytical methods provide feedback on the successful formation of the desired amorphous structure, allowing for quality control and consistent pharmaceutical product production
3Productivity
If previous synthesis methods are used, then the process is well-documented and reproducible, but the product is incorrectly identified as amorphous when it is actually crystalline
Solution Approach 1:
The patent implements rigorous characterization using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) to accurately identify and confirm the amorphous form of BisEDT. These techniques provide definitive feedback on the physical state of the product, correcting previous misidentifications and ensuring accurate form characterization for quality control and regulatory purposes
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 amorphous BisEDT form exhibits enhanced stability, solubility, and bioavailability, making it suitable for treating pulmonary diseases and diabetic foot infections through inhalation or topical administration, with aerosolized microparticles demonstrating high deposition efficiency in the lungs and effective microbial biofilm reduction.
Implementation Method 1
combining the product of (a) with a solution of 1,2-ethanedithiol in a solvent selected from the group consisting of acetone, acetonitrile, 1,2-dichloroethane, dimethyl sulfoxide, ethyl acetate, isopropanol, methyl tert-butyl ether, and mixtures thereof, under conditions and for a time sufficient for formation of a precipitate which comprises the amorphous form of BisEDT
Implementation Method 2
formation of a precipitate which comprises the amorphous form of BisEDT
Implementation Method 3
the amorphous BisEDT has a glass transition at about 101° C.
Implementation Method 4
The X-ray powder diffraction pattern of amorphous BisEDT does not contain any distinct peaks
Implementation Method 5
the differential scanning calorimetry thermogram of amorphous BisEDT comprises an exothermic peak at about 168° C.
Data Source
AI summary
The invention relates to an amorphous form of bismuth-1,2-ethanedithiol (BisEDT). Methods of making amorphous BisEDT and methods of use are also provided.