Amoxicillin Trihydrate Micronization for Solubility
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Solution Overview
Problem
Enzymatically produced amoxicillin trihydrate has reduced solubility due to its higher purity, which is a drawback compared to traditional chemically produced forms that contain organic contaminants, leading to decreased dissolution rates.
Innovation Solution
Control the surface area of amoxicillin trihydrate between 1.0 to 2.5 m2/g, reducing particle size through micronization to enhance solubility while minimizing contaminants like dichloromethane, isopropanol, pivalic acid, and triethyl amine, and incorporating enzymatic synthesis with biocatalysts to maintain purity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional chemical synthesis is used to produce amoxicillin, then solubility is improved due to presence of organic contaminants, but purity deteriorates with significant levels of residual solvents and auxiliary chemicals
Solution Approach 1:
The patent changes the physical parameter of particle size through micronization to improve solubility. By reducing particle size and increasing surface area, the patent achieves enhanced dissolution rates without relying on organic contaminants, thus maintaining high purity while improving solubility characteristics.
2Manufacturing precision
If enzymatic processes are used to produce high purity amoxicillin, then purity is improved with minimal contaminants, but solubility deteriorates due to absence of contaminant-induced dissolution enhancement
Solution Approach 1:
The patent applies micronization to change the physical parameter of particle size, thereby improving solubility and dissolution rates of high-purity enzymatically produced amoxicillin without compromising purity. This physical modification allows the patent to achieve both high purity and improved solubility simultaneously.
3Quantity of substance
If particle size is reduced to improve solubility, then dissolution rate is improved, but manufacturing complexity increases due to need for precise surface area control
Solution Approach 1:
The patent establishes specific surface area ranges (1.0 to 2.5 m²/g) as optimal parameters for achieving improved dissolution rates. By defining these precise parameter ranges, the patent simplifies manufacturing control while maintaining enhanced solubility and dissolution characteristics.
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 optimized amoxicillin trihydrate composition exhibits improved solubility and efficacy in treating bacterial infections, with faster dissolution in aqueous environments and increased bioavailability, maintaining high purity and stability even at elevated temperatures, thus addressing the solubility and stability issues of enzymatically produced forms.
Implementation Method 1
contacting 6-aminopenicillanic acid and an ester or an amide of D-4-hydroxyphenylglycine or a salt thereof together with a biocatalyst in water
Implementation Method 2
controlling the surface area of amoxicillin trihydrate between 1.0 to 2.5 m2/g, reducing particle size through micronization to enhance solubility
Data Source
AI summary
The present invention relates to amoxicillin trihydrate compositions having a surface area of from 1.0 to 2.5 m2·g−1 that are free of organic contaminants such as dichloromethane, isopropanol, pivalic acid and triethyl amine and that have a purity of from 97.0% to 99.99%. Furthermore, the present invention relates to a method for the preparation of said amoxicillin trihydrate compositions and to the use of said compositions for the treatment of a bacterial infection.