Method for controlling acidity of piperacillin sodium and tazobactam sodium for injection

Abstract

The invention relates to a method for controlling the acidity of piperacillin sodium and tazobactam sodium for injection. The method is characterized by comprising the following steps of: (1) determining the weight ratio of piperacillin sodium to tazobactam sodium at 2:1; (2) determining the weight ratio of ion exchange resin to water at 1:25, mixing with one or two of piperacillin sodium and tazobactam sodium, and adding alkali in a salifying process while stirring, wherein the alkali is prepared into an alkali solution with certain concentration; (3) controlling the acidity of liquid medicine subjected to filter pressing at 5.8-6.2, filtering, and preparing filtrate into a liquid injection, an infusion solution, a powder injection and a freeze-dried powder injection according to a pharmaceutic conventional requirement. According to the method, the pH value is 6.13, the moisture is 0.7%, and the bacterial endotoxin content of every 1 mg of a product is less than 0.060 EU; the acidity of a finished product is 5.8-6.5, so that the stability of the product is enhanced, and the compliance of the medication of a patient is changed.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a method for reducing related substances of piperacillin sodium and tazobactam sodium for injection. Background technique [0002] Piperacillin / tazobactam is a compound broad-spectrum antibiotic composed of piperacillin sodium and β-lactamase inhibitor tazobactam sodium. Combination of this drug with aminoglycosides such as amikacin, gentamicin or tobramycin has antibacterial effects against Pseudomonas, Serratia, Klebsiella, indole-positive Proteus, Proteus Sensitive strains of Weedenella, other Enterobacteriaceae, and Staphylococcus have a synergistic bactericidal effect. 2. The combination of this drug and some cephalosporins has a synergistic antibacterial effect on certain sensitive strains of Escherichia coli, Pseudomonas, Klebsiella and Proteus. 3. When this drug is used in combination with probenecid, probenecid can reduce the excretion of piperacillin in renal tubules...

AI Technical Summary

Problems solved by technology

5. Combination of this drug with anticoagulant drugs such as heparin, coumarin, and indanedione may cause coagulation disorder and increase the risk of bleeding

Invention patent CN102018713B discloses a piperacillin / tazobactam pharmaceutical composition, in which the weight ratios of piperacillin sodium to tazobactam sodium are 8:1, 4:1 and 2: 1. Use the method of ion exchange resin to exchange HT in piperacillin acid and tazobactam acid with Na+ to obtain the pharmaceutical composition of piperacillin acid sodium and tazobactam acid sodium, and there is no carbon dioxide in the composition Residue, after being prepared into a preparation, the drug piperacillinate sodium and tazobactam sodium composition is obtained, but the carbon dioxide in the drug will always remain in the water, so the stability of the preparation and insoluble particles are always unsolvable Yes, the main factor affecting the stability of piperacillin sodium and tazobactam sodium for injection is the acidity in the drug, so it needs to be researched and developed: the alkali added in the process of salt formation needs to be prepared into an alkali solution of appropriate concentration, and stirred while adding , so that the reaction is complete, the acid will not be included, and the acidity of the liquid medicine after the press filtration will not change; 2. Control the acidity of the liquid medicine after the press filtration. The acidity of the dry product will only be 6.0~6.4