The GMP Standard Plant Design Of300t/a Of Nitrofurantoin

As the raw material of nitrofuran kind of antibacterial drugs, nitrofurantoin has asuperiority of low price and stable efficacy. It is the first choice of treating and preventingnephritis, cystitis, urethritis, pyelitis and someother urinary tract infection diseases. Themarket prospect of nitrofurantoin is very considerable：the market capacity of nitrofurantoinin according with USPS32standards and EP6standards in the United States and Europeexceeded1000tons per year and the sale was more than200million dollars, with an annualgrowth rate of3%to5%. As living standards and medical level gradually improved, thequality of drugs had to meet more strict demands. The implementation of the new GMP leadto higher requirements to new API workshops. Therefore, in order to successfully pass theGMP certification and produce high quality products, the newly built nitrofurantoin plantmust be in accordance with the GMP and some related standards for design. This designintended to build a workshop getting an annual output of300tons of nitrofurantoin based onGMP standards.The content of this design mainly includes: process route choice, process design,material calculation, energy calculation, process equipment selection and calculation,workshop layout design, labor safety and some other non-process design, etc.In my design, the production process as follows: Firstly, a mixture of hydrazine hydrate,carbamide and acetone was reacted under certain conditions, after the condensation reaction,acetone semicarbazone was obtained. Secongdly, the acetone semicarbazone reacted withmethyl chloroacetate and then afforded1-aminoethane hydantoin by hydrochloric acidthrough the hydrolysis reaction. Finally,5-nitro-furfural diethyl was hydrolyzed byhydrochloric acid and then reacted with1-aminoethane hydantoin to obtained nitrofurantoin.Moreover, the yield of acetone semicarbazone,1-aminoethane hydantoin and nitrofurantoinwas88%,88%and90.9%, respectively. And the final yield was70.2%. The advantages ofthis production process is that this design possesses short process flow, low impurity content,less "three wastes" treatment, no need purification and less equipment investment, what’smore, it can directly produced to meet the requirements of the product.This design is based on the original old workshop. The original workshop’s space structure is not designed on the standards of new workshop project, so in the new plant design,we should not only consider the production technology, production scale and otherrequirements, but also make a comprehensive consideration to make best use of oldworkshop’s space available integrating the original workshop’s actual situation. The data ofthis design referred to the original nitrofurantoin workshop documentation and relevantmanuals. Plant layout and equipment selection were finally determined in the basis ofrepeated discussion and fine measurement. The new plant had been successfully constructedand had been running well.