DE3911321A1 - Process for the preparation of cefazolin sodium salt - Google Patents

Abstract

Process for the preparation of crystalline cefazolin sodium by dissolving cefazolin in water together with a sodium donor and crystallizing by concentrating this solution.

Description

DE-OS 27 52 443 is the production of crystalline Cefazolin sodium salt

described.

According to this procedure, cefazolin sodium is combined in one Water-ethanol mixture crystallizes at -10 to -30 ° C and then freeze-dried.

It has now been found that the very water-soluble Cefazolin sodium (aqueous solution = application form) is reflected Expect from aqueous solution by concentrating in the form can be crystallized by needles.

The invention thus relates to a method for Production of crystalline sodium cefazolin, thereby is characterized in that with cefazolinic acid in water a sodium donor in solution and through Concentrate this solution crystallized.

As sodium donors e.g. Sodium hydroxide, Sodium acetate, sodium bicarbonate, preferably sodium 2 ethyl hexanoate and sodium hydroxide. The Sodium hydroxide can for example be in the form of a 1n solution be used.  

The sodium salt solution is expediently prepared at room temperature. Subsequently, in general sterile filtered and then concentrated.

By gentle concentration, if possible in a vacuum, expediently at temperatures below 60 ° C., preferred between 20 and 40 ° C, cefazolin sodium is already at Room temperature or at lower temperatures around 0 ° C crystallized out.

By adding alcohols during the isolation - ethanol is preferably used - to the cefazolin sodium salt suspension, the crystallization is completed, although weak cooling, for example to about 0 ° C., can also be favorable. The crystal suspension is then diluted by further ethanol addition, the crystals are suctioned off, washed with ethanol and dried in vacuo.

The crystallization with concentration can also by Azeotropic distillation takes place. The water is there partially or entirely by means of a tractor, e.g. n-butanol, for example at reduced pressure Temperatures around 40 ° C away, where already the Crystallization takes place. Cafazolin sodium is used in this Case, for example, from butanol or butanol water isolated.

It was not foreseeable that the compared to DE-OS 27 52 443 significantly simplified measures, in particular also with regard to the very good solubility of the product would lead to a well crystallizing sodium salt.

example 1

25 g of cefazolinic acid are suspended in 125 ml of water and dissolved by adding 1N sodium hydroxide solution to pH 8.5. The solution is clarified with 0.5 g of activated carbon, then concentrated in vacuo at a bath temperature of F40 ° C. to 30-40% of the initial volume, with crystallization occurring. 125 ml of ethanol are added to the crystal suspension, the mixture is stirred at room temperature for 1 hour and stored at 0 ° C. overnight. The crystals are filtered off, washed with 50 ml of ethanol and dried in vacuo at room temperature.
Yield: 22.83 g (80% of theory)
(The mother liquor can be recycled or cefazolinic acid can be recovered by acidification to pH 1.9.)

Example 2

20 g of cefazolinic acid are suspended in 125 ml of water and mixed with 1N sodium hydroxide solution at max. pH 8.5 dissolved. The mixture is clarified with 0.5 kg of activated carbon and the water is azeotropically distilled from the filtrate after addition of 250 ml of n-butanol, which can be added if necessary, until finally cefazolin sodium is present in crystalline form in water / butanol or butanol . The mixture is cooled to room temperature, the crystals are filtered off and washed with 100 ml of ethanol. Drying in vacuum at room temperature, in a stream of nitrogen.
Yield: 24.9 g (95% of theory).

Claims (3)

1. A process for the preparation of crystalline cefazolin sodium, characterized in that cefazolin is dissolved in water with a sodium dispenser and crystallized by concentrating this solution. 2. The method according to claim 1, characterized in that the sodium donor sodium hydroxide, sodium 2 is ethylhexanoate or sodium acetate. 3. The method according to claims 1 to 2, characterized characterized in that the concentration under Azeotroping is performed.