JPH0219119B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a process for making solid sodium amoxicillin by spray drying a slurry of sodium amoxicillin in a mixture of water and t-butanol. Solid sodium amoxicillin is produced by precipitation (as in British Patents Nos. 1241844 and 1286199), but on an industrial scale residual reagents such as triethylamine or sodium 2-ethylhexanoate or excess residual It has been found that the product is poor due to contamination caused by the solvent. Solid sodium amoxicillin has also been produced by freeze-drying (as in British Patents Nos. 1,527,557 and 1,543,317), but this requires very expensive equipment to produce the quantities required for industrial use. Furthermore, the extremely low temperatures required require long periods of time and reduce yields from a given device. An object of the present invention is to provide a method for obtaining solid sodium amoxicillin in a desired particle size at low cost and in a short time without contamination caused by residual reagents or residual solvents. The method of the invention consists of spray drying a slurry of sodium amoxicillin in aqueous t-butanol in a spray dryer. The spray drying device used in the method of the present invention may be any known suitable device, and its type is not particularly limited.
Spray drying equipment sprays and disperses the fluid containing the material to be dried through a nozzle in hot air.The nozzle types include the pressure type, which pressurizes the fluid and sprays it out, and the rotation type, which supplies the fluid onto a high-speed rotating disk and scatters it using centrifugal force. There are different types, but you can use any of them. In the present invention, since the fluid components are flammable, it is desirable to use nitrogen or the like as the hot air to keep the oxygen concentration at a safe concentration. The spray drying apparatus used in the examples of the present invention is a closed cycle type spray drying apparatus. FIG. 1 is a schematic diagram showing an example thereof. The apparatus mainly consists of a drying chamber 1, a product cyclone 2, an exhaust fan 3, a condenser/scrubber 4, a nitrogen fan, a heat exchanger 5, a nozzle 6 and a feed pump. The apparatus was set up to run simultaneously while discharging cyclone products. First, nitrogen is introduced to reduce the oxygen concentration below the safe concentration, and the _N2 introduction temperature is
Gas flow rate, condenser temperature, etc. were adjusted. Aqueous t-butanol sodium amoxicillin slurry 8 was then injected through nozzle 6 into the drying chamber. The dry product and gas were sent from the bottom to a cyclone for separation. The experimental results are shown in the table below. From the results in the following table, it can be seen that spray drying of a slurry using an aqueous t-butanol solution exhibits excellent effects. The inlet temperature 7 is preferably about 180°C, and the outlet temperature 9 is preferably about 120°C.
The latter can be adjusted by cooling N ₂ 10. Also t
-Butanol The aqueous solution preferably contains about 1.5 parts of t-butanol per 3.6 parts of water.

【table】

Table: The purity and physical properties of the four batches of spray-dried solid sodium amoxicillin were suitable for commercial use after sterilization, such as with ethylene oxide. In the production of the feed solution to the dryer (dissolution step above), finely powdered amoxicillin trihydrate (potency 845mc) was used.
g/mgm) of water per Kg of amoxicillin trihydrate
A slurry was prepared in an aqueous t-butanol solution using 2.4 parts of t-butanol and 1.5 parts of t-butanol, and the slurry was kept at 25°C. A 1.97N aqueous sodium hydroxide solution was continuously added to this slurry to give an approximately 2% excess (1.23/Kg).

【table】

【table】

Table: The pressure during the spray drying process was varied to obtain the desired particle size. A spray drying operation under aseptic conditions using a pressure nozzle produces sterile solid sodium amoxicillin, which can be directly filled into bottles under aseptic conditions. The antibacterial properties and clinical uses of amoxicillin are well known in the medical literature for the oral use of its trihydrate. For parenteral administration, it is preferred to inject the aqueous solution, which requires conversion of the insoluble trihydrate to the highly water-soluble sodium salt, as in the method of the present invention. The results of parenteral administration of sodium amoxicillin aqueous solutions can be found, for example, in DA Spiker et al.'s “Drug Kinetics of Amoxicillin: Dose-dependence after Intravenous, Oral and Intramuscular Administration”.
(Antimicrobial Agents and Chemotherapy,
11, 132 (1977)) and SA Hill et al., “Pharmacokinetics of parenterally administered amoxicillin” (Journal
of Infection 2, 320-332 (1980)).

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing an example of a spray drying apparatus used in the present invention.

Claims (1)

[Claims] 1. A method for producing solid sodium amoxicillin, which comprises spray-drying a slurry of sodium amoxicillin in an aqueous solution of t'-butanol in a spray dryer. 2. The method according to claim 1, wherein the inlet temperature of the spray drying device is about 180°C and the outlet temperature is about 120°C. 3. The method of claim 1, wherein the slurry to be spray dried comprises about 1.5 parts t-butanol to every 3.6 parts water.