Field of the Invention
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The present invention provides an improved process for preparing nitrofurantoin monohydrate.
Background of the Invention Nitrofurantoin is chemically known as 1 -[(5-nitro-2-furyl)methylideneamino] imidazolidine-2,4-dione and is extensively used as an antibacterial agent for urinary tract infections. It is rapidly absorbed in the gastrointestinal tract and reaches high concentration in the urine. Furadantin and Macrodantin are the most commonly used trade marks.
Nitrofurantoin was first disclosed in US Patent No. 2,610,181 which describes a process for preparation of nitrofurantoin comprising reaction of 1-amino-hydantoin sulphate in an aqueous solution containing acetic acid and sulfuric acid with 5-nitro-2-furfural diacetate in ethyl alcohol at reflux condition for one and half hour to give nitrofurantoin. The nitrofurantoin obtained from the above process was recrystallized using a mixture of water and ethanol.
Nitrofurantoin exists as an anhydrous and monohydrate form. GB 954 841 discloses nitrofurantoin monohydrate in the form of stable prismatic crystals. The patent discloses that stable crystalline form of 1-[(5-nitro-2-furyl)methylideneamino]imidazolidine-2,4-dione is obtained by drying 1-[(5-nitro-2-furyl)methylideneamino] imidazolidine-2,4-dione to a temperature not exceeding 8O°C. The nitrofurantoin monohydrate so obtained consists of yellow transparent prisms that are stable to storage in presence of water vapor.
Journal of Crystallographic and Spectroscopic Research, Vol 23, No 9, 1993 describes the preparation and X-ray crystal structures of two monohydrate forms of Nitrofurantoin designated as Form I, crystallized in the monoclinic space group P2i/n and Form II, crystallized in the orthorhombic space group Pbca. Nitrofurantin monohydrate Form I was obtained by recrystallization from a hot acetone-water solution (volume ratio 2:1).

Nitrofurantoin monohydrate Form II was obtained by recrystallization from hot acetone-water solution (volume ration 1:1).
Alternatively, the present invention provides a novel process for preparing nitrofurantoin monohydrate.
Summary of the Invention It is a principal aspect of the present invention to provide a process for the preparation of nitrofurantoin monohydrate.
It is another aspect of the present invention to provide a simple and commercially viable process for preparing nitrofurantoin monohydrate, wherein the process involves minimum steps and less time.
It is yet another aspect of the present invention to provide a simple and commercially viable process for preparing nitrofurantoin monohydrate, wherein the process employs solvents that are safe and easy to handle.
In accordance with one exemplary embodiment of the present invention, there is provided a simple and commercially viable process for preparing nitrofurantoin monohydrate, wherein the process comprises the steps of suspending nitrofurantoin in a polar organic solvent, adding water to resultant mixture, heating the mixture and isolating the nitrofurantoin monohydrate.
Brief Description of the Drawings Further objects of the present invention together with additional features contributing thereto and advantages accruing there from will be apparent from the following description of preferred embodiments of the invention which are shown in the accompanying drawing figures wherein : Figure 1 is the X-ray powder diffraction pattern of nitrofurantoin monohydrate

Figure 2 is the differential scanning calorimetric (DSC) curve of nitrofurantoin
monohydrate.
Figure 3 is the thermogravimetric analysis (TGA) of Nitrofurantoin monohydrate.
Detailed Description of the Invention While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.
The present invention provides an improved process for preparing nitrofurantoin monohydrate using crude nitrofurantoin. The nitrofurantoin monohydrate according to the present invention is obtained in different crystalline forms, preferably Form II.
The present invention provides a process for the preparation of nitrofurantoin monohydrate, wherein the process comprising the steps of suspending nitrofurantoin in polar organic solvents, filtering to obtain crystals, adding water, heating the resultant suspension and isolating nitrofurantoin monohydrate.
The nitrofurantoin employed for the preparation of nitrofurantoin monohydrate is prepared by methods described in prior-art.
According to the present invention, the solvent used in the process is selected from any suitable polar organic solvents, preferably dimethyl sulfoxide, dimethyl formamide, dimethyl acetamide and formic acid.
In an exemplary procedure of the present invention, the process is provided, wherein nitrofurantoin is suspended in dimethyl sulfoxide and refluxed to obtain a clear solution, charcoal is added to the solution, filtered through hyflo bed followed by slow addition of water to the filtrate to obtain crystals. The crystals were suspended in water, heated to 80-

85°C and the temperature maintained for 2-5 hrs. The reaction mixture is cooled to 25-35°C and filtered to isolate nitrofurantoin monohydrate.
Powder X-rav Diffraction (PXRD)
The powder X-ray diffraction measurements of the present invention were carried out using PANalytical, X'Pert PRO powder diffractometer equipped with gonimeter of 9/9 configuration and X'Celerator detector. The Cu-anode X-ray tube was operated at 40 kV and 30 mA. The experiments were conducted over the 29 range of 2.0º-50.0 º, 0,030° step size and 50 seconds step time.
Differential Scanning Calorimetry (DSC)
The DSC measurements were carried out using the instrument TA Q1000 of TA instruments. The experiments were performed at a heating rate of 5.0 ºC/minute over a temperature range of 30ºC-300 °C purging with nitrogen at a flow rate of 5Oml/minute.
Thermo gravimetric Analysis (TGA)
TGA measurements were recorded on the instrument Mettler Toledo TGA/SDTA 85 le and TA Q5OOO of TA instruments. The experiments were performed at a heating rate of 10.0 ºC/min over a temperature range of 3O°C-3OO°C purging with nitrogen at a flow rate of 2Oml/min and 25ml/min.
The nitrofurantoin monohydrate of the present invention is characterized by powder X-ray diffraction pattern, differential scanning calorimetric pattern (DSC) and thermogravimetric analysis.
The nitrofurantoin monohydrate is characterized by an powder X-ray diffraction pattern as shown in Figure 1 with peaks at 12.27 13.93 0.2, 24.61 and 28.12, 31.32 ± 0.2 two-theta values.
The nitrofurantoin monohydrate is further characterized by DSC with an endothermic peak at 274.47 º C as shown in Figure 2.

The nitrofurantoin monohydrate has water content of about 7.61 % which is analyzed by its TGA data as shown in Figure 3.
The following non-limiting examples illustrate specific embodiments of the present invention. They are, not intended to be limiting the scope of present invention in any way.
Example 1 Nitrofurantoin was suspended in dimethyl sulfoxide at 25-30ºC and stirred for 15 minutes. The reaction mixture was heated to 8O-85°C following which charcoal carbon (PS-133) was added and heating continued for next 30 minutes. The reaction mass was filtered through hyflo bed and washed with 50 ml dimethyl sulfoxide. The above filtrate was taken into another round bottom flask and 750 ml DM water was slowly added in 45-50 minutes at 25-30ºC. The reaction mass was stirred for 30 minutes at 25-30ºC and filtered. The product was washed with DM water twice at 25-30ºC and vacuum dried for 30 minutes. The wet material was taken into another round bottom flask and 700 ml DM water was added at 25-30 °C. The reaction mixture was heated to 8O-85°C, maintained for three hours and cooled at 25-30ºC. The reaction mixture was filtered, washed with 100 ml DM water and 200ml methanol. The isolated solid was dried at 25-30ºC.
Example 2 Nitrofurantoin was suspended in dimethyl formamide at 25-30ºC and stirred for 15 minutes. The reaction mixture was heated to 8O-85°C following which charcoal carbon (PS-133) was added and heating continued for next 30 minutes. The reaction mass was filtered through hyflo bed and washed with 50 ml dimethyl formamide. The above filtrate was taken into another round bottom flask and 750 ml DM water was slowly added in 45-50 minutes at 25-30ºC. The reaction mass was stirred for 30 minutes at 25-30ºC and filtered. The product was washed with DM water twice at 25-30ºC and vacuum dried for 30 minutes. The wet material was taken into another round bottom flask and 700 ml DM water was added at 25-30 °C. The reaction mixture was heated to 8O-85°C, maintained

for three hours and cooled at 25-30ºC. The reaction mixture was filtered, washed with 100 ml DM water and 200ml methanol. The isolated solid was dried at 25-30ºC.
Certain modifications and improvements of the disclosed invention will occur to those skilled in the art without departing from the scope of invention, which is limited only by the appended claims.

We Claim:
1. An improved process for preparing nitrofurantoin monohydrate, the
process comprising
(i) suspending nitrofurantoin in a polar organic solvent;
(ii) adding water to resultant mixture;
(iii) heating the mixture; and
(iv) isolating the nitrofurantoin monohydrate.
2. The process according to claim 1, wherein the polar organic solvent is
preferably selected from dimethylsulfoxide, dimethylformamide, dimethylacetamide and
formic acid.
3. The process according to claim 1, wherein the heating of mixture is
preferably done at a temperature of about 8O-85°C.
4. The process according to claim 1, wherein the step of isolating the
nitrofurantoin monohydrate comprises cooling the mixture and filtering the resultant to
obtain nitrofurantoin monohydrate