The method of separation of 2,5-dinitrourea

 

(57) Abstract:

The inventive method includes the recrystallization technical dinitrourea in a single ethanol exposure at 20oC for 1 h followed by treatment of the suspension dinitrourea in the mother solution, 3 to 5 times in an ultrasonic or rotary pulsation device at 5-15oFrequency ripple 2 - 5 Hz. table 1.

The invention relates to a method for producing 2,5-isosorbide dinitrate treatment (dinitrourea). Dinitrourea used to get drugs, which are effective means to coronary diseases, including for the prevention and relief of angina.

A known method of producing dinitrourea in which recrystallization technical dinitrourea in aqueous ethanol with a concentration of 50 to 90% (I).

The disadvantage of this method is that the obtained dinitrourea has a needle-like crystals form, which are easily are painted pellet-pellet mass (TM) drying and sieving, which disturbs its composition. In addition, needle crystals of dinitrourea when pressing tablets form a solid matrix, which significantly okogie get tablets pharmaceutical preparation based dinitrourea is what he is mixed with excipients (sucrose, starch and so on), the resulting mixture is granulated. The granules of the tablet mass must have a size of 0.2 to 1.5 mm When the granulation inevitably formed and smaller granules that need to be weeded out. When preparing TM is used dinitrourea with particles of needle-like form when the screening is chipping particles dinitrourea from the surface of the granules, otselenie small fraction of TM obtained enriched dinitrourea and commodity fraction depleted. Therefore it is necessary at the stage of mixing TEE to dose nitrosorbid abundant, however, and it does not always produce the desired results.

The aim of the invention is to obtain an isometric particles that enhance the stability of the composition of the TM containing dinitrogen, and reducing the time raspadaemosti tablets.

This goal is achieved by the fact that the suspension dinitrourea in the fallopian aqueous ethanol after recrystallization at a temperature of 5 15oC handle 3 to 5 fold in the acoustic apparatus providing a pulse frequency of 2 to 50 kHz.

The lower limits of the ratio of the circulation of the suspension and the pulsation frequency in the acoustic when the pulse frequency of less than 2 kHz not give the desired result.

In table.1 shows the results of analyses of key quality indicators TM and tablets "nitrosorbid", obtained at different process parameters.

Upper bounds for the multiplicity of processing and frequency ripple acoustic apparatus due to expediency. The increase in the number of processing slurry over 5 does not affect the quality of the TEE and ready tablets, but worsens filtering the suspension and reduces the efficiency of the process. The industry produces acoustic apparatus with a radiation frequency up to 50 kHz.

Temperature limits process of suspension due to the need to reduce losses of dinitrourea. At a temperature of more than 15oC dramatically increases the solubility of dinitrourea in aqueous ethanol, resulting in lower output. Processing at temperatures less than 5oC does not significantly affect the quality of the product and its output. However, increasing the energy cost of cooling the suspension, which makes the processing at temperatures less than 5oC uneconomic.

Example 1.

The solvent is poured 100 l of pure ethanol in it load 50 kg technical dinitrourea, the suspension is heated to dastore ethyl alcohol and zakolerovat it to a temperature of +5oC.

Then in the mold dispense hot solution of dinitrourea, cool the contents of the 20oC and incubated for 1 h, the Suspension is cooled to +5oC +10oC and pumped 4 times through the rotary pulsation apparatus in a closed loop mold apparatus.

After processing is complete, the suspension was poured onto the filter, uterine ethyl alcohol is expressed in the vacuum receiver, dinitrogen washed with water and dried. The resulting dinitrourea mixed in the required proportions with available domestic components tablemats, granularit on the plate granulator, and then tabletirujut in a known manner.

Get tablets nitrosorbid" content dinitrourea 10,1% raspadaemost tablets in water for 8-9 minutes, the remaining indicators meet all the requirements of the VFS.

Example 2.

In the mold pour 100 ml of ethyl alcohol, load of 50 g of dinitrourea and boil the mass at a temperature of 78oC for 30 minutes the Solution is metered into the apparatus, filled with 50 ml of aqueous ethanol and incubated for 1 h at a temperature of 10 20oC.

The unit is mounted with dispenser CHECK-2T with output power GE kHz.

Turning on the generator, the suspension is dispersed 3-fold at a temperature of 10 15oC. Upon completion of processing, the generator is disconnected, dinitrogen separated from the mother liquor, washed with about 1.D. water and dried.

The resulting dinitrourea with isometric particles form granularit. TM satisfies all the requirements of the VFS, the content of dinitrourea 10,3% raspadaemost tablets 7-9 minutes

The method of separation of 2,5-dinitrourea, including recrystallization technical dinitrourea in aqueous ethanol extract at 20oC for 1 h, characterized in that, after recrystallization suspension of dinitrourea in the mother solution process 3 to 5 times in an ultrasonic or rotary pulsation apparatus 5 15oFrequency ripple 2 50 Hz.

 

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