Ceftiofur Sodium Crystalline Form Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional Ceftiofur sodium is amorphous, making it unstable and difficult to purify, which is undesirable in pharmaceutical manufacturing due to its chemical instability and poor handling properties.
Innovation Solution
A novel crystalline form of Ceftiofur sodium is developed through a process involving dissolution in water, optional addition of an organic solvent, and inclusion of alkaline or alkaline earth metal salts, followed by filtration to isolate the crystalline product directly from the reaction mixture, avoiding the use of amines and membrane filtration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional amorphous Ceftiofur sodium is used, then the preparation process is simple, but the product is unstable and difficult to purify
Solution Approach 1:
The patent applies phase transition by converting amorphous Ceftiofur sodium into a crystalline form. The process involves dissolving the amorphous salt in water and inducing crystallization through controlled conditions (pH adjustment, temperature control, and addition of crystallization promoters). This phase transition from amorphous to crystalline state resolves the contradiction by providing a product that maintains ease of manufacture while achieving superior stability and purifiability.
Solution Approach 2:
The patent employs parameter changes by systematically adjusting critical parameters during the conversion process: pH (maintaining at 7-9 using buffers), temperature (controlling crystallization at 4-25°C), concentration (optimizing saturation levels), and adding specific ions (calcium, magnesium, or zinc ions as crystallization promoters). These parameter changes enable the transformation from unstable amorphous form to stable crystalline form while maintaining manufacturing feasibility.
2Ease of manufacture
If conventional amorphous Ceftiofur sodium is used, then the preparation process is simple, but purification is difficult
Solution Approach 1:
The crystallization process enables effective purification by exploiting the phase transition from dissolved state to crystalline solid. Impurities remain in the mother liquor while pure Ceftiofur sodium crystallizes out, allowing simple filtration and washing to achieve high purity (99% or higher). This resolves the contradiction by maintaining process simplicity while dramatically improving purification capability.
Solution Approach 2:
The patent applies extraction principles by separating the desired crystalline product from impurities through selective crystallization. The process extracts pure Ceftiofur sodium crystals from the reaction mixture, leaving impurities in the aqueous phase. This is followed by simple filtration and washing steps that efficiently remove remaining impurities, achieving high purity without complex purification procedures.
3Reliability
If crystalline form is developed, then stability and purity are improved, but the process complexity increases
Solution Approach 1:
The patent utilizes phase transition as the core mechanism to achieve crystallization from a simple aqueous solution. By controlling pH, temperature, and adding minimal crystallization promoters (calcium, magnesium, or zinc ions at 0.1-5% concentration), the process achieves reliable crystallization without requiring complex equipment or multiple processing steps. The simplicity of the phase transition approach maintains process feasibility while delivering stable crystalline product.
Solution Approach 2:
The patent applies self-service principles by allowing the crystallization process to proceed with minimal intervention. The system uses naturally occurring phenomena (solubility changes with temperature, pH-dependent solubility, and spontaneous nucleation) to drive crystallization. The added ions (Ca²⁺, Mg²⁺, or Zn²⁺) act as crystallization promoters that facilitate the process without requiring complex control systems, enabling the process to be self-regulating and simple to operate.
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 crystalline form exhibits improved stability, purity, and physical characteristics, such as higher bulk density and reduced solubility, maintaining potency over a long shelf period and simplifying industrial-scale production.
Implementation Method 1
a process for the preparation of Ceftiofur sodium as a crystalline product, the crystalline Ceftiofur sodium prepared according to our invention
Implementation Method 2
isolating Ceftiofur sodium directly from the reaction mass
Data Source
AI summary
The present invention relates to novel polymorph of Ceftiofur sodium as a crystalline product. The present invention also provides a process for the preparation of crystalline Ceftiofur sodium of formula (I).