Field of the Invention This invention, in general relates to novel polymorphs of triclabendazole. More particularly, the present invention provides the polymorphs of triclabendazole, directed as Forms I, II, III, IV, V of triclabendazole, wherein Forms I and II are the anhydrous forms, Forms III, IV and V are the solvates and an amorphous form VI of triclabendazole. Further, the process for preparing the same are disclosed.
Background of the Invention
Triclabendazole (TCB), 5-chloro-6-(2,3-dichlorophenoxy)-2-(methylthio)benzimidazole, is a halogenated benzimidazole compound that possesses high activity against immature and adult stages of the liver fluke, Faciola hepatica. The intensive use of TCB in endemic areas of facioliasis has resulted in the development of liver flukes resistant to this compound.
H

Triclabendazole
US 4,197,307 discloses the process for the preparation of triclabendazole, wherein 4-chloro-5-(2,3-dichlorophenoxy)-l,2-benzenediamine is reacted with carbondisulfide to give cyclic benzimidazole thione, which is further subjected to alkylation reaction with dimethyl sulfate to give triclabendazole, which is recrystallized from a mixture of alcohol and water to give pure triclabendazole, which is crystalline and having the similar pXRD pattern shown in figure-1. In this patent, triclabendazole polymorphic forms are not disclosed.
EP 0224249 discloses amorphous triclabendazole wherein, triclabendazole is dissolved in basic condition followed by addition of acid to precipitate triclabendazole solid as an amorphous. The resultant amorphous form contains around 10% crystalline triclabendazole.
Scientia Pharmaceutica (Sci.Pharm) 58, 55-67 (1990) paper teaches melt film contains mixtures of crystals of triclobendazole Form I and Form II, in the form of needles and plates, without providing any further information on relative amounts of the polymorphs present. The DSC thermogram of the melt film compound shows a sharp melting

endotherm at 165° C attributed to melting of Form II and a small endotherm at 176° C attributed to melting of Form I. However, melt-film preparation is not a viable method to produce pure polymorphs on commercial scale.
The present invention provides novel polymorphic forms of triclobendazole characterized as anhydrous forms, solvates and an amorphous form.
Summary of the Invention The present invention relates to novel crystalline polymorphs of the triclabendazole, referred to herein after Form I, Form II as anhydrous forms. Form III, Form IV, Form V as solvates and Form VI as an amorphous, characterized by X-ray powder diffraction pattern. Infrared absorption spectrum, thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC) and/or moisture content.
Furthermore, the present invention is also directed to the process for the preparation of novel crystalline polymorphs of the triclabendazole and amorphous form by using different solvent systems and conditions.
In accordance with one preferred embodiment of the present invention, there is provided a higher mehing anhydrous crystalline triclabendazole Form I with a moisture content of 0.1-0.3 % (By KF method) and crystalline triclabendazole polymorphic Form-I is characterized by an x-ray powder diffraction pattern having peak at about 10.62 (±) 0.2, 16.45 (±) 0.2, 20.67 (±) 0.2, 25.37 (±) 0.2, 25,84 (±) 0.2 and 27.85 (±) 0.2 two-theta.
In accordance with another preferred embodiment of the present invention, there is provided an anhydrous crystalline triclabendazole Form II with a moisture content of 0.1-0.3 % (By KF method) and crystalline triclabendazole polymorphic Form-II is characterized by an x-ray powder diffraction pattern having peak at about 18.02 (±) 0.2, 19.84 (±) 0.2, 23.95 (±) 0.2, 25.68 (±) 0.2, 27.17 (±) 0,2 and 30.57 (±) 0.2 two-theta.
In accordance with yet another preferred embodiment of the present invention, there is provided a crystalline triclabendazole Form III as a l-methyl-2-pyrrolidone solvate with a solvent content of 11-14 % supported by thermogravemetric analysis (TGA) and a moisture content of 0.3-0.7% (By KF method). Preferably, the solvate is a mono 1-

methyl-2-pyrrolidone solvate. Interestingly the solvate shows a sharp melting endotherm at 123°C in DSC and no evidence of the desolvation.
Further embodiment of the present invention is to provide a crystalline triclabendazole Form IV as a 2-butanol solvate with a 2-butanol content of 7-10 % supported by TGA and moisture content of 0.7-1.2 % (By KF method). Preferably, the solvate is a hemibutanolate.
In other embodiment of the present invention, there is provided a crystalline triclabendazole Form V as a N,N-dimethylacetamide (DMA) with a DMA content of 18-22 % supported by TGA and moisture content of 2-4 % supported by KF method. Preferably, the solvate is a mono DMA solvate.
Furthermore, according to another embodiment of the present invention, there is provided a novel stable Form VI of triclabendazole in amorphous state with moisture content of 1-4 % (by KF method) and glass transition onset at 52° C supported by modulated DSC.
In accordance with yet another embodiment of the present invention, there is provided a process for the preparation of triclabendazole crystalline polymorphic forms designated as I, II, III, IV & V. Triclabendazole polymorphic form I & II are anhydrous forms and form III, IV & V are hydrated forms.
In accordance with another embodiment of the present invention, there is provided a process for the preparation of pure amorphous Triclabendazole.
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 Form I of Triclabendazole. Figure 2 is the DSC of Form I of Triclabendazole.

Figure 3 is the X-ray powder diffraction pattern of Form II of Triclabendazole.
Figure 4 is the DSC of Form II of Triclabendazole.
Figure 5 is the X-ray powder diffraction pattern of Form III of Triclabendazole.
Figure 6 is the DSC of Form III of Triclabendazole.
Figure 7 is the TGA of Form III of Triclabendazole.
Figure 8 is the X-ray powder diffraction pattern of Form IV of Triclabendazole.
Figure 9 is the DSC of Form IV of Triclabendazole.
Figure 10 is the TGA of Form IV of Triclabendazole.
Figure 11 is the X-ray powder diffraction pattern of Form V of Triclabendazole.
Figure 12 is the DSC of Form V of Triclabendazole.
Figure 13 is the TGA of Form V of Triclabendazole.
Figure 14 is the X-ray powder diffraction pattern of Form VI of Triclabendazole.
Figure 15 is the DSC of Triclabendazole amorphous Form VI.
Figure 16 is the TGA of Triclabendazole amorphous Form VI.
Figure 17 is the IR of Triclabendazole amorphous Form VI.
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 describes the crystalline triclabendazole Form I and Form II, which exists as anhydrous forms and Form III, Form IV and Form V in solvated forms along with the amorphous Form VI and are intended to be encompassed with in the scope of the present invention. The said forms are differ from each other in their physical properties, spectral data and method of preparation and characterized by their X-ray powder diffraction patterns, thermo gravimetric analysis (TGA) and/or by infra red absorption spectrum (IR).
Powder X-ray Diffraction (PXRD)
The said polymorphs of the present invention are characterized by their X-ray powder diffraction pattern. Thus, the X-ray diffraction patterns of said polymorphs of the invention were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of 9/9 configuration and X'Celerator detector. The Cu-anode X-ray tube

was operated at 40kV and 30mA. The experiments were conducted over the 29 range of 2.0°-50.0°, 0.030° step size and 50 seconds step time.
Diffrential Scanning Calorimetry (DSC)
The DSC measurements were carried out on Mettler Toledo 822 Star* and TA QIOOO of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 150ml/min and 50ml/min. Standard aluminum crucibles covered by lids with three pin holes were used.
DSC Glass Transition
The glass transition temperature (Tg) of the amorphous triclabendazole was measured on
TA QIOOO of TA instruments with modulated DSC software. The experiments were
performed at a heating rate of 3.0°C/min up to a final temperature of 250° with
modulation amplitude ±1.0°C, modulation period 80sec and nitrogen purging at a flow
rate of 50ml/min. Standard aluminum crucibles covered by lids with five pin holes were
used.
Thermogravimetric Analysis fTGA)
TGA was recorded on out using the instrument Mettler Toledo TGA/SDTA 851' and TA Q5000 of TA instruments. The experiments were performed at a heating rate of 10.0 °C/min over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 20ml/min and 25ml/min.
Karl-Fisher
Water content was determined on Metrohm Karl-Fisher titrator (Model: 794 Basic Titrino) using pyridine free single solution (Merck, Mumbai) with sample mass between 450mg to 550mg.
Infrared spectroscopy
Fourier transform infrared (FT-IR) spectra were recorded with a Perkin-Elmer spectrum one spectrophotometer. The samples were prepared as 13mm thickness potassium bromide discs by triturating 1 to 2mg of sample with 300mg to 400mg of KBR by applying pressure of about 1000 Ibs/sq inch. Then theses discs were scanned in the spectral range of 4000 to 650 cm-1 with a resolution of 4 cm-1

Crystalline triclabendazole Form I is characterized by powder X-ray diffraction pattern as shown in Figure 1 with peaks at 5.13, 9.79, 10.25,10.62, 10.91, 12.87, 15.38, 16.45, 17.42, 17.57, 17.91, 18.77, 19.05, 19.63, 20.13, 20.67, 21.31, 21.96, 23.40, 24.12,24.82, 25.37, 25.84, 26.32, 26.85, 27.11, 27.84, 28.84, 29.27, 30.24, 31.32, 32.12, 34.93, 35.29, 36.20,38.08,38.51, 39.81,40.52, 43.39, 44.91, and 48.15 ± 0.2 29 values.
Crystalline triclabendazole Form I is further characterized by DSC with an endothermic
o
peak at 177 C corresponding to melting of the product as shown in Figure 2. (The water content determined by the Karl-Fisher method is 0.1 to 0.3%)
The present invention also provides the process for the preparation of crystalline triclabendazole Form I, which comprises contacting triclabendazole in a solvent or mixture of solvents, from about ambient temperature to reflux temperature. The solvent used herein selected from the group comprising Isopropyl alcohol, methanol. Ethyl acetate, chloroform, 1,4-dioxane, Tetrahydrofuran, nitromethane, diethyl ether, t-butylether, acetone, acetonitrile. Dimethyl formamide, 2-methoxy ethanol, ethanediol, dimethyl carbonate (DMC), xylene, toluene, ethanol and mixtures thereof. The obtained solid is filtered under suction followed by vacuum drying. Triclabendazole used herein selected from anhydrous or hydrated forms.
Crystalline triclabendazole Form II is characterized by powder X-ray diffraction pattern as show in Figure 3 with peaks at 8.981, 10.93, 11.43, 13.19, 16.71, 17.27, 18.01, 18.81, 19.48, 19.82, 22.03, 23.09, 23.93, 24.72, 25.67, 26.34, 26.54, 26.94, 27.15, 27.45, 28.17, 30.56, 30.79, 31.44, 33.39, 34.79, 36.17, 36.91, 39.54, 40.25, 43.87, 44.46, 45.38, 46.10, 47.60, and 48.93 ± 0.2 20 values.
Crystalline triclabendazole Form II is further characterized by DSC with an endotherm at 166 C corresponding melting of the product as shown in Figure 4. (The water content determined by the Karl-Fisher method is 0.1 to 0.3%)
The present invention also provides the process for the preparation of crystalline triclabendazole Form II, which comprises contacting triclabendazole in a solvent or

mixtures thereof, such as methanol, ethylacetate, heptane and water, from about 0°C to reflux temperature. Triclabendazole used herein group selected from anhydrous or hydrated form.
Crystalline triclabendazole Form III characterized by powder X-ray diffraction pattern as shown in Figure 5 with peaks at 6.12, 11.37, 12.25, 13.50, 15.63, 16.68, 16.77, 17.61, 18.40, 20.16, 22.7, 24.62, 24.95, 26.31, 28.16, 30.90, and 35.72 ± 0.2 29 values.
Crystalline triclabendazole Form III is further characterized by DSC with a sharp endothermic peak at 123°C corresponding to mehing of the product as shown in Figure 6. No evidence of solvent loss (desolvation) is observed in the DSC thermogram of the Form III, Figure 6. Crystalline triclabendazole Form III is 1-methylpyrrolidone solvate having 11-14%, which is analyzed by its TGA data as shown in Figure 7. Preferably, the solvate is a mono l-methyl-2-pyrrolidone solvate. (The water content determined by the Karl-Fisher method is 0.3 to 0.7 %).
The present invention also provides a process for the preparation of crystalline triclabendazole Form III, which comprises crystallizing triclabendazole from 1-methyl-2-pyrrolidone, using the method of slow or fast evaporation. Triclabendazole Form III may also be prepared by anti-solvent method from the l-methyI-2-pyrrolidone/water mixture. The obtained solid is filtered under suction followed by vacuum drying. Triclabendazole used herein group selected from anhydrous or hydrated form.
Crystalline triclabendazole Form IV characterized by powder X-ray diffraction pattern as shown in Figure 8 withpeaks at 6.11, 10.6, 11.33,12.3, 12.94, 13.14, 13.81, 14.80, 16.51, 16.98, 17.54, 18.35, 18.58, 19.5, 20.51, 20.62, 21.76, 22.53, 23.47, 24.15, 24.54, 25.23, 25.60, 26.02, 26.78, 27.32, 28.89, 30.80, 32.31, and 35.11 ± 0.2 28 values.
Triclabendazole Form IV, is further characterized by the DSC (Figure 9), it shows three melting endothermic peaks; first at about 102°C attributed to desolvation and later at \66°C and 176°C due to melting of the product. Crystalline triclabendazole Form IV is 2-butanol solvate having 7-10 %, which is analyzed by its TGA data as shown in Figure 10.

Preferably, the solvate is a hemibutanolate. (The water content determined by the Karl-Fisher method is 1.0 to 1.6 %).
The present invention also provides a process for the preparation of crystalline triclabendazole Form IV, which comprises slow or fast evaporation of saturated solution of triclabendazole from a solvent, such as 2-butanol, at ambient temperature for several days. Form IV may also prepared by contacting triclabendazole in a solvent such as 2-butanol, from about ambient temperature to reflux temperature. The obtained solid is filtered under suction followed by vacuum drying. Triclabendazole used herein group selected from anhydrous or hydrated form.
Crystalline triclabendazole Form IV can also be prepared by seeding the saturated solution,of Triclabendazole in 2-butanol. Triclabendazole used herein group selected from anhydrous or hydrated form.
Crystalline triclabendazole Form V is characterized by powder X-ray diffraction pattern as shown in Figure 11 with peaks at 8.80, 9.74, 10.66, 12.41, 13.2, 14.30, 15.72, 17.43, 17.87, 18.48, 19.04, 19.62, 20.07, 21.72, 22.38, 22.66, 23.5, 24.87, 25.17, 26.20, 27.07, 27.62, 28.20, 31.2, 33.24, 35.15, 44.24, 46.01 ± 0.2 20 values.
Crystalline triclabendazole Form V is further characterized by the DSC (Figure 12), which shows a broad endothermic peak at an extrapolated onset temperature ranging from 45-80°C, corresponding to desolvation followed by melting of the product. Crystalline triclabendazole Form V is N,N-dimethylacetamide (DMA) with a DMA content of 18-22 %, which is analyzed by its TGA data shown in Figure 13 and moisture content of 2-4 % supported by KF method. Preferably, the solvate is a mono DMA solvate.
The present invention also provides the preparation of crystalline triclabendazole Form V, which comprises slow or fast evaporation of saturated solution of triclabendazole in a solvent, such as N,N-dimethylacetamide (DMA), at ambient temperature for several days. Triclabendazole Form V may also be prepared by slurrying or seeding in DMA solvent. The crystalline product was isolated by filtration followed by drying, e.g. at room temperature and atmospheric pressure. The resulting DMA solvate crystalline form has water content typically ranging from approx. 2.0 to 4.0 % by weight, preferably 1.0-2.0 %

by weight determined by the KF method. Triclabendazole used herein selected from the group consisting of but not limited to anhydrous or hydrated form.
Amorphous triclabendazole Form VI is characterized by powder X-ray diffraction pattern as shown in Figure 14.
Amorphous triclabendazole Form VI is further characterized by the DSC, which shows the glass transition onset for the amorphous form exactly at 52°C as measured by modulated DSC. The DSC thermogram (Figure 15) of triclabendazole amorphous shows three characteristic peaks; first endothermal peak at an extrapolated onset temperature ranging 60-70°C corresponding loss due to the moisture, an exothermic peak at an extrapolated onset temperature ranging from 126 to 155°C, corresponding to the transition from amorphous phase to an anhydrous crystalline phase which is identified with a peak at 142°C, and a second endothermal peak at 165°C (maxima), corresponding to the complete melting of the product.
The amorphous form contains the water up to approximately 1.0 to 3.0 % by weight, preferably 1.0 to 2,0 % determined by TGA (Figure 16) and the Karl-Fisher method. Amorphous triclabendazole Form VI is further characterized by IR with absorption bands (cm'*) at .1448, 1574 respectively; as depicted in Figure 17.
The present invention also provides the preparation of Amorphous triclabendazole Form VI, which comprises preparing a solution of triclabendazole in a solvent selected from the group consisting of alcoholic solvents, apolar aprotic solvents, lower aliphatic ketones, ether solvents, chlorinated solvents, esters, hydrocarbon solvents including aliphatic, alicyclic, aromatic compounds, and/or mixtures thereof, followed by removal of the solvent and recovering the isolated amorphous triclabendazole Form VI.
The solvent used is selected from the group consisting of but not limited to acetonitrile, acetone, methanol, ethanol, ethylacetate, chloroform, methylene dichloride, diethyl ether, isopropyl ether, petroleum ether, hexane, heptane, pentane, cyclohexane, toluene and mixtures thereof The removal of the solvent may include the processes known in the

literature such as distillation, distillation under vacuum, evaporation, spray drying, freeze-drying, filtration, filtration under vacuum, decantation and centrifugation.
The amorphous triclabendazole Form VI can also be prepared by spray drying the solution of triclabendazole in a solvent. The solvent used herein selected from the group consisting of but not limited to lower alcohol, ketone, apolar aprotic solvent such as methanol, ethanol, isopropyl alcohol, propanol, butanol, iso-butanol, acetone, dimethylformamide, dimethylsulfoxide, nitromethane, acetonitrile, water or mixture thereof preferably water, methanol, acetone acetonitrile, propanol, n-butanol or mixture thereof
The present invention also provides a process for the preparation of crystalline triclabendazole Form II, which comprises heating either amorphous or crystalline Form IV of triclabendazole. The triclabendazole Form II can also be prepared by slurrying the amorphous triclabendazole Form VI in a solvent. The solvent used herein are selected from the group consisting of but not limited to hexane, heptane, pentane, cyclohexane, toluene or mixtures thereof
The present invention also provides a process for the preparation of crystalline triclabendazole Form I, which comprises heating any crystalline form of triclabendazole selected from the group consisting of Form III and Form V. Form I may also be preprared by slurrying Form VI in a solvent selected form the group consiting of but not limited to isopropyl ether, petroleum ether, ditheyl ether and methyl tertiary butyl ether.
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.
TRICLABENDAZOLE FORM I
Example 1
Preparation of Triclabendazole Form-I using product patent process US 4,197.307: Triclabendazole was crystallized in a mixture of alcohol and water to give crystalline triclabendazole, which was having similar pXRD pattern and matching with Polymoprhic
form-1.

Example 2
Preparation of Triclabendazole Form I using Solvent -Anti solvent technique
100 ml of heptane was placed into a round bottom flask and heated to reflux temperature.
To this solution added Ig of triclabendazole dissolved in 8ml of 1,4-dioxane for a period
of Ihour at reflux temperature. Then the reaction mass was stirred for 2 hours at this
temperature followed cooling to room temperature. The separated solid was filtered and
suction dried under vacuum at room temperature and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form I
Example 2
Preparation of Triclabendazole Form I
2g of triclabendazole was dissolved in 14 ml of methanol at hot condition. Then the
reaction mass was stirred for 2hours at reflux temperature followed by cooling to room
temperature. The solid obtained was isolated by filtration and dried under vacuum at
atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form I
Example 3
Preparation of Triclabendazole Form-I
2g of triclabendazole was dissolved 8 ml of 1,4-dioxane at hot condition. The resulting saturated solution was allowed for slow evaporation at ambient temperature. The solid obtained was isolated by filtration and dried under vacuum at atmospheric pressure. XRD of wet sample showed it to be triclabendazole form I
Example 4
Preparation of Triclabendazole Form I
100 ml of heptane was placed into a round bottom flask and heated to reflux temperature.
To this solution added Ig of triclabendazole dissolved in 10 ml of chloroform for a period
of Ihour at reflux temperature. Then the reaction mass was stirred for 2 hours at this
temperature followed cooling to room temperature. The separated solid was filtered and
suction dried under vacuum at room temperature and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form I
Example 5
Preparation of Triclabendazole Form I

Ig of triclabendazole was suspended in 10 ml of heptane refluxed for 2 hours followed by cooling to room temperature. The solid obtained was filtered and suction dried under vacuum at room temperature and atmospheric pressure. XRD of wet sample showed it to be triclabendazole form I
TRICLABENDAZOLE FORM II
XRD of wet sample showed it to be triclabendazole form II
Example 6
Preparation of Triclabendazole Form II
Ig of triclabendazole was suspended in 20 ml of IP A refluxed for 2 hours followed by
cooling to room temperature. The solid obtained was filtered and suction dried under
vacuum at room temperature and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form II
TRICLABENDAZOLE FORM-III
Example 7
Preparation of Triclabendazole Form III
2g of triclabendazole was dissolved in 10 ml of IPA at hot condition. The resulting
saturated solution was allowed for slow evaporation at ambient temperature for several
days. The resulting crystalline solid was isolated by filtration.
XRD of wet sample showed it to be triclabendazole form III
Example 8
Preparation of Triclabendazole Form III
2g of triclabendazole was dissolved in 10 ml of IPA at hot condition. The resulting
saturated solution was allowed for fast evaporation at ambient temperature for several
days. The resulting crystalline solid was isolated by filtration.
XRD of wet sample showed it to be triclabendazole form III
Example 9
Preparation of Triclabendazole Form III
2g of triclabendazole was dissolved in 3ml of 1-Methyl 2-pyrrolidinone at ambient
temperature. The resulting saturated solution was allowed for slow evaporation at
ambient temperature for several days. The resulting crystalline solid was isolated by
filtration.
XRD of wet sample showed it to be triclabendazole form III

Example 10
Preparation of Triclabendazole Form III
Ig of triclabendazole was dissolved in 3ml of 1-Methyl 2-pyrrolidinone at ambient
temperature. To this saturated solution 10ml of water was added slowly forming a gummy
residue. The resulting gummy residue was then freed by stirring for overnight at ambient
temperature. The solid compound obtained was isolated by filtration and dried at room
temperature and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form III
TRICLABENDAZOLE FORM IV
Example 11
Preparation of Triclabendazole Form IV
Ig of triclabendazole was dissolved in 10ml of 2-butanol at hot condition. The resulting
saturated solution was allowed for slow evoparation at ambient temperature. The resulting
solid was isolated by filtration.
XRD of wet sample showed it to be triclabendazole form IV
Example 12
Preparation of Triclabendazole Form IV
Ig of triclabendazole was dissolved in 10ml of 2-butanol at hot condition. The resulting
saturated solution was allowed for fast evaporation ambient temperature. The resulting
solid was isolated by filtration.
XRD of wet sample showed it to be triclabendazole form IV
Example 13
Preparation of Triclabendazole Form IV
Ig of triclabendazole was dissolved in 10ml of 2-butanol at hot condition. The resulting
saturated solution was stirred for 4 hours at ambient temperature. The resulting solid was
isolated by filtration and dried at room temperature and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form IV
Example 14
Preparation of Triclabendazole Form IV
Ig of triclabendazole was dissolved in 10ml of 2-butanol at reflux temperature. The reaction mass was stirred for 2 hours at reflux temperature, slowly cool to ambient temperature. The solid obtained was isolated by filtration and dried at room temperature and atmospheric pressure.

XRD of wet sample showed it to be triclabendazole form IV TRICLABENDAZOLE FORM V
Example 15
Preparation of Triclabendazole Form V
Ig of triclabendazole was dissolved in 3ml of DMA at hot condition. The resulting
saturated solution was allowed for slow evaporation at ambient temperature. The resulting
crystalline product was isolated by filtration.
XRD of wet sample showed it to be triclabendazole form V
Example 16
Preparation of Triclabendazole Form V
Ig of triclabendazole was dissolved in 3ml of N,N-Dimethyl Acetamide at hot condition.
The resulting saturated solution was allowed for fast evaporation at ambient temperature.
The resulting crystalline product was isolated by filtration.
XRD of wet sample showed it to be triclabendazole form V
Example 17
Preparation of Triclabendazole Form V
Ig of TCB was dissolved in 3ml of DMA at ambient temperature and added 10ml of
diethyl ether was added as an anti solvent. The resulting clear solution was allowed for
slow evaporation at ambient temperature for several days. The solid compound was
isolated by filtration and dried at room temperature and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form V.
TRICLABENDAZOLE AMORPHOUS
Example 18
Preparation of Triclabendazole Amorphous
30 ml of diethyl ether placed in round bottom flask and heated to reflux temperature. Then slowly add saturated acetone solution (Ig of triclabendazole dissolved in 10 ml of acetone) at reflux temperature. The reaction mass was stirred for over night at reflux temperature and cooled to room temperature. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihr results free solid product (2g, 98%) of amorphous triclabendazole.

Example 19
Preparation of Triclabendazole Amorphous
30 ml of diethyl ether was placed in a round bottom flask and heat to reflux temperature. Then slowly add methanol solution (Ig of triclabendazole dissolved in 10 ml of methanol) at reflux temperature. The reaction mass was stirred for over night and followed by cooling to room temperature. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihr results free solid product (2g, 98%) of amorphous triclabendazole.
Example 20
Preparation of Triclabendazole Amorphous
30 ml of diethyl ether was placed in a round bottom flask and cool to 0°C. Then slowly added THF solution (Ig of triclabendazole was dissolved in 6 ml of THF). The reaction mass was stirred for over night and followed by cooling to room temperature. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihr results free solid product (2g, 98%) of amorphous triclabendazole.
Example 21
Preparation of Triclabendazole Amorphous
50 ml of diethyl ether was placed in a round bottom flask and cool to 0°C. Then slowly added chloroform solution (Ig of triclabendazole dissolved in 16 ml of chloroform) at 0°C. The reaction mass was stirred for over night and followed by cooling to room temperature. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihr results free solid product (2g, 98%) of amorphous triclabendazole.
Example 22
Preparation of Triclabendazole Amorphous
30 ml of diethyl ether was placed in a round bottom flask and cool to 0°C. Then slowly added ethyl acetate solution (Ig of triclabendazole dissolved in 16 ml of ethyl acetate) at 0°C. The reaction mass was stirred for over night and followed by cooling to room temperature. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihr results free solid product (2g, 98%) of amorphous triclabendazole.
Example 23
Preparation of Triclabendazole Amorphous

20 ml of diethyl ether was placed in a round bottom flask and cool to 0°C. Then slowly added 1,4-dioxane solution (Ig of triclabendazole dissolved in 5 ml of 1,4-dioxane) at 0°C. The reaction mass was stirred for over night and followed by cooling to room temperature. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihr results free solid product (2g, 98%) of amorphous triclabendazole.
Example 24
Preparation of Triclabendazole Amorphous
lOg of triclabendazole was dissolved in 100ml of methanol at hot condition. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihour results free solid product of amorphous triclabendazole.
Example 25
Preparation of Triclabendazole Amorphous
5g of triclabendazole was dissolved in 125 ml of acetone at hot condition. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihour results free solid product of amorphous triclabendazole.
Example 26
Preparation of Triclabendazole Amorphous
5g of triclabendazole was dissolved in 125 ml of chloroform at hot condition. The resuhing clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihour results free solid product of amorphous triclabendazole.
Example 27
Preparation of Triclabendazole Amorphous
5g of triclabendazole was dissolved in 125 ml of THF at hot condition. The resulting clear solution was distilled off completely under vacuum at 50°C leaving white foam. Additional drying under reduced pressure for Ihour results free solid product of amorphous triclabendazole.
Example 28
Conversion of Triclabendazole Amorphous to Anhydrous Form II by Slurrying

15 ml of heptane was placed into a round bottom flask along with 1g of amorphous triclabendazole. The mixture was then stirred at ambient temperature for 1 hour. The mixture was filtered under a vacuum of 600 mm Hg and the solid was finally dried under vacuum at ambient temperature to give the Form II of triclabendazole.
Example 29
Conversion of Triclabendazole Amorphous to Anhydrous Form I by Slurrying 15ml of IPE was placed into a round bottom flask along with Ig of amorphous triclabendazole. The mixture was then stirred at ambient temperature for Ihour. The mixture was filtered under a vacuum of 600 mm Hg and the solid was finally dried under vacuum at ambient temperature to give the Form I of triclabendazole.
Example 30
Conversion of Triclabendazole Amorphous to Anhydrous Form II by Drying 1 g of amorphous triclabendazole was taken in a clean Petri dish. The compound was then dried in a vacuum oven at 100°C under a vacuum of 600 mm Hg for 16 hours to obtain triclabendazole Form II.
Example 31
Conversion of Solvate Form III to Anhydrous Form I by Drying
1 g of triclabendazole Form III was taken in a clean Petri dish. The compound was then dried in a vacuum oven at 60*^C under a vacuum of 600 mm Hg for 16 hours to obtain triclabendazole Form I.
Example 32
Conversion of Solvate Form IV to Anhydrous Form II by Drying
1 g of triclabendazole Form IV was taken in a clean Petri dish. The compound was then dried in a vacuum oven at 60°C under a vacuum of 600 mm Hg for 16 hours to obtain triclabendazole Form II.
Example 33
Conversion of Solvate Form V to Anhydrous Form I by Drying
1 g of triclabendazole Form V was taken in a clean Petri dish. The compound was then dried in a vacuum oven at 60°C under a vacuum of 600 mm Hg for 24hrs to obtain triclabendazole Form I.
Example 34
Preparation of Triclabendazole Form IV by seeding

1 g of triclabendazole was dissolved in 10 ml of 2-butanol at hot condition. The resulting saturated solution was seeded with form IV and stirred for 1 hour at ambient temperature. The obtained solid was isolated by filtration and dried at room temperature and atmospheric pressure. XRD of wet sample showed it to be triclabendazole form IV.
Example 35
Preparation of Triclabendazole Form V by seeding
1 g of triclabendazole was dissolved in 3 ml of Dimethyl acetamide at hot condition. The
resulting saturated solution was seeded with form V and stirred for 1 hour at ambient
temperature. The obtained solid was isolated by filtration and dried at room temperature
and atmospheric pressure.
XRD of wet sample showed it to be triclabendazole form V.
While this invention has been described in detail with reference to certain preferred embodiments, it should be appreciated that the present invention is not limited to those precise embodiments rather, in view of the present disclosure, which describes the current best mode for practicing the invention, many modifications and variations, would present themselves to those skilled in the art without departing from the scope and spirit of this invention.

We Claim:
1. A crystalline triclabendazole polymorphic Form L
2. The crystalline polymorphic Form according to claim 1, wherein said form I is characterized by an X-ray powder diffraction pattern having peak at about 5.13, 9.79, 10.25,10.62, 10.91, 12.87, 15.38, 16.45, 17.42, 17.57, 17.91, 18.77, 19.05, 19.63, 20.13, 20.67, 21.31, 21.96, 23.40, 24.12,24.82, 25.37, 25.84, 26.32, 26.85, 27.11, 27.84, 28.84, 29.27, 30.24, 31.32, 32.12, 34.93, 35.29, 36,20, 38.08, 38.51, 39.81,40.52, 43.39, 44.91, and 48.15 ± 0.2 2G values.
3. A process for preparing crystalline triclabendazole polymorphic Form-I comprising the steps of:
(a) dissolving triclabendazole in a solvent medium and stirring the resultant at reflux temperature;
(b)cooling the resultant of step (a); and
(c) isolating the crystalline triclabendazole polymorphic Form-I.
4. The process according to claim 3, wherein the solvent is selected from methanol, ethanol, isopropyl alchohol, toluene, heptane , hexane or mixtures thereof
5. A process for preparing crystalline triclabendazole polymorphic Form-I comprising the steps of:

a) dissolving triclabendazole in a solvent medium;
b) adding anti-solvent in the resultant of step (a); and
c) isolating the crystalline triclabendazole polymorphic Form-I.

6. The process according to claim 5, wherein the solvent is selected from alcohol, ether or chlorinated solvents.
7. The process according to claim 6, wherein the alcohol is selected from methanol, ethanol and isopropyl alcohol, ether is selected from tetrahydrofuran and 1, 4-dioxane, and chlorinated solvent is chloroform.

8. The process according to claim 5, wherein the anti-solvent is selected from hexane, heptane, diisopropyl ether, water or mixtures thereof.
9. A process for preparing crystalline triclabendazole polymorphic Form-I comprising the steps of:
(a) dissolving triclabendazole in a solvent medium at hot condition; (b)evaporating the resultant saturated solution of step (a); and (c) isolating the crystalline Triclabendazole Polymorphic Form-I.
10. The process according to claim 9, wherein solvent group is selected from alcohol, ketone, ester, chlorinated, aromatic hydrocarbons.
11. The process according to claim 10, wherein the alcohol is selected from methanol, ethanol, n-butanol, isopropyl alcohol, ketone solvent is selected from acetone, ester solvent is selected from ethylacetate, aromatic hydrocarbon is selected from toluene, xylene, chlorinated solvent is selected from chloroform, dichloromethane, other solvents are selected from dimethylformamide, nitromethane.
12. A crystalline triclabendazole polymorphic Form II.
13. The crystalline polymorphic Form according to claim 12, wherein said form II is characterized by an X-ray powder diffraction pattern having peak at about 18.02 (±) 0.2, 19.84 (±) 0.2, 23.95 (±) 0.2, 25.68 (±) 0.2, 27.17 (±) 0.2 and 30.57 (±) 0.2 two-theta.
14. The crystalline polymorphic Form according to claim 13, wherein said form II is characterized by an X-ray powder diffraction pattern having peak at about 8.99 (±) 0.2, 10.94 (±) 0.2, 11.45 (±) 0.2, 13.20 (±) 0.2, 16.80 (±) 0.2, 17.28 (±) 0.2, 18.02 (±) 0.2, 18.91 (±) 0.2, 19.50 (±) 0.2, 19.84 (±) 0.2, 22.05 (±) 0.2, 23.11 (±) 0.2, 23.95 (±) 0.2, 24.74 (±) 0.2, 25.69 (±) 0.2, 26.50 (±) 0.2, 26.91 (±) 0.2, 27.17 (±) 0.2, 27.46 (±) 0.2, 28.18 (±) 0.2, 30.57 (±) 0.2, 31.48 (±) 0.2, 33.40(±) 0.2, 34.80 (±) 0.2, 36.18 (±) 0.2, 37.00 (±) 0.2, 39.56 (±) 0.2, 40.28 (±) 0.2, 42.90(±) 0.2, 44.38 (±) 0.2, 45.34 (±) 0.2, 46.10 (±) 0.2, 47.59(±) 0.2 and 48.93 ± 0.2 20 values.

15. The crystalline polymorphic Form according to claim 12, wherein the said
form is having a substantially similar X-ray powder diffraction pattern as shown in
figure-3.
16. The crystalline polymorphic Form according to claim 12, wherein said form is characterized by a differential scanning calorimetry (DSC) as shown in figure-4.
17. A process for preparing crystalline triclabendazole polymorphic Form-II comprising the steps of:

(a) dissolving triclabendazole in a solvent;
(b) adding the resultant solution of step (a) into anti solvent; and
(c) isolating the crystalline triclabendazole Form-II.
18. The process according to claim 17, wherein the solvent is selected from
methanol, ethyl acetate, acetone or mixtures thereof.
19. The process according to claim 17, wherein the anti solvent is selected from heptane and water.
20. A process for preparing crystalline triclabendazole polymorphic Form-II comprising the steps of:

(a) dissolving triclabendazole in a solvent;
(b) heating anti-solvent to reflux temperature;
(c) adding triclabendazole solution of step (a) into the anti solvent; and
(d) isolating the crystalline triclabendazole Form-II.

21. The process according to claim 20, wherein the solvent is selected from methanol, ethyl acetate, acetone or mixtures thereof.
22. The process according to claim 20, wherein the anti solvent is selected from heptane and water.

23. A process for preparing crystalline triclabendazole polymorphic Form-II
comprising the steps of:
(a) dissolving triclobendazole in a solvent;
(b) maintaining the resultant solution of step (a) at reflux temperature;
(c) cooling the resultant of step (b); and
(d) isolating the triclabendazole From-II.

24. The process according to claim 23, wherein the solvent is Isopropyl alcohol.
25. A crystalline triclabendazole polymorphic Form-Ill.
26. The crystalline polymorphic Form according to claim 25, wherein said form III is characterized by an X-ray powder diffraction pattern having peak at about 12.38 (±) 0.2, 18.51 (±) 0.2, 24.70 (±) 0.2 and 30.98 (±) 0.2 two-theta.
27. The crystalline polymorphic Form according to claim 26, wherein said Form III is characterized by an X-ray powder diffraction pattern having peak at about 6.28 (±) 0.2, 11.51 (±) 0.2, 12,38 (±) 0.2, 13.56 (±) 0.2, 16.87 (±) 0.2,18.52 (±) 0.2, 20.32 (±) 0.2, 22.70 (±) 0.2, 24.70 (±) 0.2, 25.05 (±) 0.2, 26.35 (±) 0.2, 28.28 (±) 0.2 and 30.98 (±) 0.2.
28. The crystalline polymorphic Form according claim 25, wherein said form is having a substantially similar X-ray powder diffraction pattern as shown in figure-5.

29. The crystalline polymorphic Form according claim 25, wherein said form is characterized by a differential scanning calorimetry (DSC) as shown in figure-6 and thermo gravimetric analysis (TGA) as shown in figure-7.
30. The crystalline Triclabendazole polymorphic Form-Ill according to claim 25, wherein said form III is a solvate containing 11-14 % of 1-methylpyrrolidone.
31. A process for preparing crystalline triclabendazole polymorphic Form-Ill
comprising the steps of:

(a) dissolving triclabendazole in 1-methyl pyrrolidone at ambient
temperature;
(b) evaporating the resultant saturated solution of step (a); and
(c ) isolating the triclabendazole Form-Ill.
32. The process according to claim 31, wherein the solvent evaporation is either slow or fast.
33. A process for preparation of Triclabendazole crystalline Form-Ill comprising the steps of:
(a) dissolving triclabendazole in 1-methyl pyrrolidone;
(b) adding anti-solvent to the resuhant of step (a) solution; and
(c) isolating triclabendazole Form-Ill.
34. The process according to claim 33, wherein the anti-solvent is water.
35. A crystalline triclabendazole polymorphic Form-IV.
36. The crystalline polymorphic Form according to claim 35, wherein said form IV is characterized by an X-ray powder diffraction pattern having peak at about 18.29 (±) 0.2, 20.56 (±) 0.2, 24.47 (±) 0.2 and 30.74 (±) 0.2 two-theta.
37. The crystalline polymorphic Form according to claim 36, wherein said form IV is characterized by an X-ray powder diffraction pattern having peak at about 6.05 (±) 0.2, 11.27 (±) 0.2, 12.15 (±) 0.2, 12.88 (±) 0.2, 13.08 (±) 0.2, 13,73 (±) 0.2, 14.20 (±) 0.2,14.74 (±) 0.2, 16.45 (±) 0.2, 16.89 (±) 0.2, 17.69 (±) 0.2, 18.29 (±) 0.2, 18.83 (±) 0.2, 19.18 (±) 0.2, 19.43 (±) 0.2, 20.56 (±) 0.2, 21.22 (±) 0.2, 21.68 (±) 0.2, 22.46 (±) 0.2, 23.40 (±) 0.2, 24.06 (±) 0.2, 24.47 (±) 0.2, 25.14 (±) 0.2, 25.23 (±) 0.2, 25.95 (±) 0.2, 26.64 (±) 0.2, 26.64 (±) 0.2, 27.30 (±) 0.2, 28.82 (±) 0.2, 30.74 (±) 0.2, 32.11 (±) 0.2, 32.43 (±) 0.2, 33.29 (±) 0.2, 34.30 (±) 0.2, 35.01 (±) 0.2, 35.64 (±) 0.2, 36.31 (±) 0.2, 37.04 (±) 0.2,and 38.20 ± 0.2 two theta.
38. The crystalline polymorphic Form according to claim 35, wherein said form is having a substantially similar X-ray powder diffraction pattern as shown in figure-8.

39. The crystalline polymorphic Form according to claim 35, wherein said form is characterized by a differential scanning calorimetry (DSC) as shown in figure -9 and thermo gravimetric analysis (TGA) as shown in figure -10.
40. The crystalline polymorphic Form according to claim 35, wherein said form is a solvate containing 7-10 % of 2 -butanol.
41. A process for preparation of Triclabendazole crystalline Form-IV
comprising the steps of:
(a) dissolving triclabendazole in 2-butanol;
(b) evaporating the resultant saturated solution of step (a) or cooling to
ambient temperature;
(c) optionally seeding with form IV; and
(d) isolating Triclabendazole Form-IV

42. The process according to claim 41, wherein the evaporation is either slow or fast.
43. The process according to claim 41, wherein the ambient temperature is 20-
30°C.
44. A crystalline triclabendazole polymorphic Form-V.
45. The crystalline polymorphic Form according to claim 44, wherein said form
V is characterized by an X-ray powder diffraction pattern having peak at about 18.48 (±)
0.2, 23.50 (±) 0.2, 24.86 (±) 0.2, 26.20 (±) 0.2 and 30.73 (±) 0.2 two-theta.
46. The crystalline polymorphic Form according to claim 45, wherein said form
V is characterized by an X-ray powder diffraction pattern having peak at about 8.80 ± 0.2,
9.74 ± 0.2, 10.66 ± 0.2, 12.41 ± 0.2, 13.2 ± 0.2, 14.30 ± 0.2, 15.72 ± 0.2, 17.43 ± 0.2,
17.87 ± 0.2, 18.48 ± 0.2, 19.04 ± 0.2, 19.62 ± 0.2, 20.07 ± 0.2, 21.72 ± 0.2, 22.38 ± 0.2,
22.66 ± 0.2, 23.50 ± 0.2, 24.87 ± 0.2, 25.17 ± 0.2, 26.20 ± 0.2, 27.07 ± 0.2, 27.62 ± 0.2,
28.20 ± 0.2, 31.2 ± 0.2, 33.24 ± 0.2, 35.15 ± 0.2, 44.24 ± 0.2 and 46.01 ± 0.2 two theta.

47. The crystalline polymorphic Form according to claim 44, wherein said form is having a substantially similar X-ray powder diffraction pattern as shown in figure-11.
48. The crystalline polymorphic Form according to claim 44, wherein said form is characterized by a differential scanning calorimetry (DSC) as shown in figure -12 and thermo gravimetric analysis (TGA) as shown in figure -13.
49. The crystalline polymorphic Form according to claim 44, wherein said form is a solvate containing 18-22 % of N,N-dimethylacetamide.
50. A process for preparation of Triclabendazole crystalline Form-V
comprising the steps of:
(a) dissolving triclabendazole in dimethyl acetamide;
(b) evaporating the resultant saturated solution of step (a);
(c) optionally seeding with Form-V; and
(d) isolating triclabendazole Form-V.

51. The process according to claim 50, wherein the evaporation is either slow or fast.
52. An amorphous form of triclabendazole, wherein said amorphous form is characterized by having a substantially similar X-ray powder diffraction pattern as shown in figure-14 and glass transition on set temp at 52° C.
53. A process for preparation of amorphous form of triclabendazole
comprising the steps of:
(a) dissolving triclabendazole in a solvent at reflux temperature;
(b) adding the resultant solution of step (a) into second solvent;
(c) removing solvent completely under reduced pressure; and
(d) isolating amorphous triclabendazole.
54. A process according to claim 53, wherein the solvent is selected from
alcohol, ketone, ester, ether and chlorinated solvents.

55. The process according to claim 54, wherein the alcohol is selected from methanol, ethanol, ketone preferably acetone, ester preferably ethyl acetate, ether preferably tetrahydrofuran, chlorinated solvent selected from chloroform or MDC, 1,4-dioxane or mixtures thereof
56. The process according to claim 53, wherein the second solvent is a non-polar solvent.
57. The process according to claim 54, wherein the non-polar solvent is selected from pentane, hexane, heptane, cyclohexane, diethyl ether, isopropyl ether and mixture thereof.
58. A process for preparation of amorphous form of triclabendazole
comprising the steps of:
(a) dissolving triclabendazole in a solvent at reflux temperature;
(b) removing solvent completely under reduced pressure; and
(c) isolating amorphous triclabendazole.

59. The process according to claim 58, wherein the solvent is selected from alcohol, ketone, ester, ether and chlorinated solvents.
60. The process according to claim 59, wherein the alcohol is selected from methanol, ethanol, ketone preferably acetone, ester preferably ethyl acetate, ether preferably tetrahydofuran or 1,4-dioxane, chlorinated solvent preferably chloroform or
mixtures thereof
61. A process for preparation of triclabendazole Form-I comprising the steps
of:
(a) suspending amorphous triclabendazole in a solvent; and
(b) isolating triclabendazole Form-I.
62. The process according to claim 61, wherein the solvent is preferably
isopropyl ether.

63. A process for preparation of triclabendazole Form-I comprising the steps
of:
(a) drying amorphous or crystalline triclabendazole Form-Ill or
crystalline triclabendazole Form-V; and
(b) isolating triclabendazole Form-I.
64. The process according to claim 63, wherein the drying is carried out under reduced pressure.
65. The process according to claim 64, wherein the drying is carried out at a temperature of about 55-60 C
66. A process for preparation of triclabendazole Form-II comprising the steps
of:
(a) suspending amorphous triclabendazole in a solvent; and
(b) isolating triclabendazole Form-II.
67. The process according to claim 66, wherein the solvent is preferably
heptane.
68. A process for preparation of triclabendazole Form-II comprising the steps
of:
(a) drying amorphous or crystalline triclabendazole Form -IV; and
(b) isolating triclabendazole Form-II.
69. The process according to claim 68, wherein the drying is carried out under
reduced pressure.

70. The process according to claim 68, wherein the drying is carried out at a
o
temperature of about 55-60 C.