Ultrasonic Induced Purification Method for Pharmaceutical Grade Guanidine Hydrochloride

Guanidine hydrochloride, white or slightly yellow lumps. Used as an intermediate for medicines, pesticides, dyes and other organic compounds. It is an important raw material for the manufacture of sulfa drugs and folic acid. It can also be used as an antistatic agent for synthetic fibers.

The purification of guanidine hydrochloride mainly uses solid crude guanidine hydrochloride to dissolve in an aqueous solution, and the difference in solubility between impurities and the product in the aqueous solution is used to crystallize solid impurities. There are many types of impurities in this process, mainly unreacted raw materials, as well as cyanamide polymers produced by side reactions. The content of various impurities is different, and the solubility gap is large. In order to ensure the maximum possible removal of various impurities, low-concentration impurities require a longer crystallization nucleation time, which leads to a longer purification cycle of guanidine hydrochloride and severely limited production capacity.

Now Wugan Pharmaceutical has disclosed a pharmaceutical grade guanidine hydrochloride ultrasonic induced purification method, which is^[1]:

(1) Add crude guanidine hydrochloride to water for stirring and mixing, and then pump into a coarse filter to remove impurities to obtain crude guanidine hydrochloride aqueous solution. The mass ratio of crude guanidine hydrochloride to water is 1.5-3:1.

(2) The crude guanidine hydrochloride aqueous solution is pumped into the ultrasonic crystallization system, and the guanidine hydrochloride clear liquid is obtained by continuous and circulating treatment, and the precipitation of fine impurities is induced. The control parameters of the ultrasonic crystallization system are: temperature 0℃～120℃, hydraulic residence time 0.5h～2h and ultrasonic power frequency 10KHz～20KHz.

(3) The guanidine hydrochloride clear liquid is pumped into the filter to remove fine impurity crystal particles, and then pumped into the decolorizer to remove the trace cyanamide impurities dissolved in the guanidine hydrochloride clear liquid to obtain a refined guanidine hydrochloride solution.

(4) Pump the refined guanidine hydrochloride solution into a crystallizer, perform crystallization purification, separate the crystals, and dry to obtain pharmaceutical grade guanidine hydrochloride.

By controlling the mixing ratio of crude guanidine hydrochloride and water, and accurately controlling the process parameters of the ultrasonic crystallization system, the production capacity of pharmaceutical grade guanidine hydrochloride is increased by 7-10 times, and the production cycle is reduced from 20-30 days to about 3 days, which greatly improve production efficiency and reduce production cycle.

References

[1] Liu Yongchao, Qian Weiwen, Han Juquan, etc. A purification method of pharmaceutical grade guanidine hydrochloride [P]. Chinese Patent: CN111302977A, 2020-03-18;