Method for controlling related substances in cefodizime sodium

Abstract

The invention provides a method for preparing cefodizime sodium for injection as well as a method for controlling related substances in the preparation method. The quality control method of the cefodizime sodium for injection disclosed by the invention is simple and feasible, stable product quality can be guaranteed, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a quality control method in the preparation process of cephalosporins, in particular to a control method for related substances in cefodizime sodium. Background technique [0002] Cefodizime sodium, English name: Cefodizime Sodium, its chemical name is (6R,7R)-7-[(2-amino-4-thiazolyl)-(methoxyimino)acetamido]-3-{[ (5-Carboxymethyl-4-methyl-2-thiazolyl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2 - Formic acid disodium salt, molecular formula: C 20 h 18 N 6 Na 2 o 7 S 4 , molecular weight: 628.64, the chemical structure is as follows: [0003] [0004] Cefodizime sodium is a third-generation cephalosporin antibiotic for injection jointly developed by Hearst Company of Germany and Russell Company of France. It is also the first third-generation cephalosporin with immune-enhancing function in the world. It was first launched in Japan under the trade name "Neucef" in 1990...

AI Technical Summary

Problems solved by technology

[0007] In order to solve its stability problem, Chinese patent ZL200910016147.9 discloses a liposomal freeze-dried preparation of cefodizime and its preparation method, but its preparation process is relatively complicated, wherein a large number of pharmaceutical excipients are added, which leads to The increase in impurity content will greatly increase the hidden dangers of drug safety. Due to the increase in impurities, it is difficult for the content of related substances to meet the requirements of the Pharmacopoeia in the test and cannot be industrialized.

In addition, the preparation yield of liposomes is very low, which causes the cost of medicines to increase greatly, and is not suitable for industrial production.

[0008] Chinese patent application document CN102258521A discloses a kind of cefodizime sodium for injection, which is prepared from cefodizime sodium, potassium clavulanate and hydroxypropyl-β-cyclodextrin (HP-β-CD), but, The injection needs to add at least 2 to 6 times the amount of potassium clavulanate and at least 1 to 4 times the amount of hydroxypropyl-β-cyclodextrin as the active ingredient cefodizime, which not only greatly increases the content of impurities in the preparation, but also The pH value of the preparation is reduced, leading to an increase in drug safety hazards. Moreover, due to the addition of a large number of excipients, the content of active ingredients in the unit preparation is reduced, which greatly reduces the efficacy and bioavailability of the drug.

Most of the currently commercially available cefodizime sodium raw materials are extremely fine powders with poor fluidity, which is unfavorable for mechanical sub-packaging and loading control; and its critical relative humidity is low, often at RH40% or below, and it is easy to absorb moisture, which requires Additional dehumidification equipment is used to strictly control the humidity level of the sub-packaging workshop below the critical relative humidity, which leads to an increase in equipment and power costs, especially in summer with high humidity; in addition, the sub-packaging speed also needs to be as fast as possible , in order to reduce the exposure time of raw materials in the air and ensure the quality of finished preparations, thus increasing the difficulty of operation

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