Active pharmaceutical ingredient synthesis is of great significance to chemical synthesis companies. What is it? Active pharmaceutical ingredients are the active ingredients used in the manufacture of pharmaceutical formulations. It is usually obtained by chemical synthesis, semi-synthesis and microbial fermentation or isolation of natural products and made by one or more chemical unit reactions and manipulations. The research on the synthesis process of active pharmaceutical ingredients is the basis of drug development and production.
Ⅰ. First, the selection and design of the synthetic route of the active pharmaceutical ingredient must have a basis and be reasonable
For new chemical entities, according to their structural characteristics, the following points are comprehensively considered:
1. The difficulty of obtaining the starting material;
2. The length of the synthesis steps;
3. The yield level;
4. Whether the post-processing and conditions of the reaction meet the industrial requirements Production and environmental protection requirements.
For drugs with known structures, the research situation of pharmaceutical preparations should be fully understood on the basis of literature research, including:
1. Feasibility;
2. Controllability;
3. Stability (whether the quality of intermediates is controllable, whether the quality of the final product is stable, whether the yield is stable);
4. Rationality (cost, price and toxicity of raw materials, reagents, solvents, etc.).
Ⅱ. The starting materials, reagents, and organic solvents for the synthesis of active pharmaceutical ingredients must be standardized, emphasizing standardization
Secondly, starting materials, reagents, and organic solvents must be standardized, and standardization is emphasized. For the control of starting materials, GMP requires the quality of products to be controlled from the source. Requirements for synthetic products:
1. Bill of materials: list the names of the materials used to synthesize active pharmaceutical ingredients, explain their respective use procedures, and identify key materials;
2. Material testing methods: clarify the quality control information of these materials.
Ⅲ. Active pharmaceutical ingredient synthesis should control the intermediate process of active pharmaceutical ingredient synthesis
Finally, intermediate processes in the synthesis of active pharmaceutical ingredients should be controlled. The control of intermediate process is divided into quality control of preparation intermediates and selection, optimization and control of process conditions and process parameters; quality control of preparation intermediates: the information provided should be able to explain how to identify key intermediates and general intermediates through research , how to achieve process control through different control of intermediates, so as to better ensure the quality of final products. Selection, optimization and control of process conditions and process parameters: The reaction device, temperature, pressure, time, solvent, pH value, illumination and other process conditions should be strictly controlled. The end of the reaction should be clearly defined (the extent to which the starting material is converted to the target product, the generation of impurities, etc.).
The research on the synthesis process of active pharmaceutical ingredients is the starting point of drug research and development, and also runs through the whole process of drug research and development. In the study of the synthesis process of active pharmaceutical ingredients, the importance of the whole process control, data accumulation, impurity analysis, starting material and reagent control is particularly emphasized, so as to determine a feasible, controllable and stable production process.
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