Cefadroxil Crystallization pH Control for Particle Size and Color Stability
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Solution Overview
Problem
Existing crystallization processes for cefadroxil result in agglomerates with large particle size distribution and low color stability, characterized by high CIE b values.
Innovation Solution
A two-step process involving an aqueous solution of cefadroxil at a pH of 7 to 9, followed by lowering the pH to 5 to 6.5, using suitable titrants like formic acid, to achieve cefadroxil crystals with small particle size distribution and high color stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional crystallization processes are used for cefadroxil, then crystallization can be achieved, but the result is agglomerates with large particle size distribution and low color stability
Solution Approach 1:
The patent applies parameter changes by controlling the pH of the aqueous solution to be between 7 and 9 during crystallization, and then lowering it to between 5 and 6.5. This specific pH control mechanism transforms the crystallization process to produce crystals with small particle size distribution (10-150 μm) and high color stability (CIE b value below 6), directly resolving the contradiction between manufacturing precision and product reliability.
2Ease of operation
If pH is not controlled during crystallization, then the process is simpler, but cefadroxil crystal explosion occurs resulting in large particle size and poor color stability
Solution Approach 1:
The patent introduces pH control as a critical parameter change to prevent crystal explosion during crystallization. By maintaining pH between 7 and 9 and then lowering to 5-6.5, the process achieves both operational feasibility and manufacturing precision, producing crystals with particle size distribution of 10-150 μm without excessive complexity.
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 yields cefadroxil crystals with particle sizes between 10 to 150 μm and low CIE b values, maintaining stability for extended storage periods, significantly improving color stability and particle size distribution compared to traditional methods.
Implementation Method 1
a process for the crystallisation of a β-lactam compound, such as cefadroxil
Implementation Method 2
bringing an aqueous solution of cefadroxil at a pH of between 7 to 9 with a suitable titrant; and lowering the pH to a value of between 5 and 6.5
Data Source
AI summary
The present invention relates to a process for the preparation of cefadroxil in crystal form, comprising: a) adding an aqueous solution of cefadroxil to a crystallisation vessel and a titrant to keep a pH in the crystallisation vessel of between 7 to 9; and b) lowering the pH in the crystallisation vessel to a value of between 5 and 6.5 to obtain a suspension of the β-lactam compound in crystal form.