The following specification claims priority from Indian Patent Application bearing Number 297/CHE/2009 dated Feb 11, 2009

FIELD OF THE INVENTION

The present invention relates to novel polymorphic forms of Dexlansoprazole designated as Form I, II, III, IV, V and VI. The present invention also relates to novel processes for the preparation of polymorphic forms I, II, III, IV, V, VI, amorphous, crystalline anhydrous and sesquihydrate of Dexlansoprazole.

The present invention further relates to novel Dexlansoprazole tartrate salt and its process for the preparation.

BACKGROUND OF THE INVENTION

Benzimidazole compounds such as Lansoprazole, Omeprazole, Rabeprazole and the like have a proton pump inhibitor like activity such as gastric acid secretion suppressing effect and gastric mucosa defensive effect. These compounds are used extensively as agents for the treatment of peptic ulcer.

In the above mentioned benzimidazoles, Lansoprazole, chemically known as 2-[[[3-methyl-4-(2s2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulflnyl]-lH-benzimidazole, is reported in Japanese Patent Application JP-A-61-50978, U.S. Pat. No. 4,628,098, JP-A-10-195068 and WO 98/21201 and has been recognized as the most potent antiulcer compound having superior activity.

These benzimidazole compounds mentioned herein have a sulfur atom which is asymmetrically substituted forming a chiral centre. WO 92/8716 discloses a pyridylmethylsulfiniyl-lH-benzimidazol compound which is enantiomerically pure, or a salt thereof and a process for producing the same. WO 99/38513 discloses a method of treating ulcers, etc. which comprises administering an optically pure (R)-lansoprazole or a pharmaceutical^ acceptable salt thereof.

(R)-2-[t[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-lH benzimidazole ((R)-Lansoprazole), represented by Formula (I), is less toxic and showed excellent antiulcer action, gastric acid secretion-inhibiting action, mucosa-protecting action, anti-Helicobacter pylori action, etc.

The method for producing (R)-2-[[[3-methyl-4-(2)2,2-trifluoroethoxy)-2-
pyridinyl]methyl]sulfinyl]-lH-benzimidazole [(R)-lansoprazole] or (S)-2-[[[3-methyl-4-
(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-lH-benzimidazole [(S)-
lansoprazole] having an antiulcer activity, is disclosed in JP-A-11-508590 (WO 97/02261), US 7169799 and US 7285668.

US 6664276 disclosed the process for the preparation of amorphous R-Lansoprazole by dissolving racemic lansoprazole in acetonitrile and fractionated by HPLC with the aid of a chiralcel column using mobile phase containing hexane/2-propanol/ethanol The fractions of the optical isomers of shorter retention time were combined and concentrated. The individual lots were combined and disslolved in ethanol and filtered. Hexane is added and evapourated to dryness to yield R (+) Lansoprazole. The said patent also disclosed the process for the preparation of R-lansoprazole sesquihydrate by dissolving amorphous Dexlansoprazole in ethanol and water. The solution is seeded and
allowed to stand at room temperature. Precipitated crystals are collected by filtration and dried to afford Dexlansoprazole sesquihydrate.

US20060057195 disclosed the process for the preparation of amorphous Dexlansoprazole by maintaining hydrated crystals of Lansoprazole R-isomer at about 20°C to about 100°C. US7271182 disclosed crystalline sodium, lithium, potassium, magnesium, calcium and barium salts of R-Lansoprazole and processes for their preparation.

The above-mentioned conventional method for the production of R-Lansoprazo!e does not necessarily satisfy the purity, solubility, preservation stability and industrial viability. Moreover the prior art process involves heating upto 100°C wherein the possibility of forming impurities are more. Thus there is a need for a better process for the preparation of Dexlansoprazole having superior properties than the ones disclosed in the prior art. Thus, the present invention relates to novel processes for preparation of amorphous and crystalline forms of Dexlansoprazole which are used in the pharmaceutical compositions.

OBJECT OF THE INVENTION

The main object of the present invention is to provide novel polymorphic forms of Dexlansoprazole designated as Form I, II, III, IV, V and VI.

Another object of the present invention is to provide novel processes for the preparation of polymorphic forms I, II, III, IV, V, VI, amorphous, crystalline anhydrous and crystalline sesquihydrate of Dexlansoprazole.

Yet another object of the present invention is to provide novel Dexlansoprazole tartrate salt and its preparation.

SUMMARY OF THE INVENTION

The present invention relates to novel polymorphic forms of Dexlansoprazole designated as Form I, II, III, IV, V and VI and processes for the preparation of the said polymorphic forms I, II, III, IV, V and VI.

The present invention also relates to novel tartrate salt of Dexlansoprazole and process for the preparation thereof,

The present invention further relates to novel processes for the preparation of amorphous, crystalline anhydrous and sesquihydrate of Dexlansoprazole.

In one aspect the present invention provides a novel crystalline form of Dexlansoprazole designated as Form I, having an X-ray diffraction pattern with peaks at 9.15,9.71, 10.39, 11.25, 13.12, 13.71, 19.47, 20.86 ± 29, shown in Fig. 1.

In another aspect, the present invention provides a process for the preparation of crystalline Dexlansoprazole Form I, which comprising the steps of; dissolving Dexlansoprazole in solvent, adding water and/or antisolvent and isolating crystalline Dexlansoprazole Form I.

In another aspect, the present invention provides a novel crystalline form of Dexlansoprazole designated as Form II, having an X-ray diffraction pattern with peaks at 8.53, 9.02, 10,14, 11,36, 11.91, 13.79, 16.88, 19.42, 21.96, 23.98 ± 26, shown In Fig.
2.

In another aspect, the present invention provides a process for the preparation of crystalline Dexlansoprazole Form II comprising the steps of dissolving Dexlansoprazole in solvent, seeding with Form II, adding water and/or antisolvent and isolating crystalline Dexlansoprazole Form II.

In another aspect, the present invention provides a novel crystalline form of Dexlansoprazole designated as Form III, having an X-ray diffraction pattern with peaks at 6.66, 14.33, 18.69, ± 29, shown in Fig. 3.

In another aspect, the present invention provides a process for the preparation of crystalline Dexlansoprazole Form III comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent and aerial drying to get Dexlansoprazole Form III.

In another aspect, the present invention provides a novel crystalline form of Dexlansoprazole designated as Form IV, having an X-ray diffraction pattern with peaks at 5.89, 17.73, 19.40, 20.32, 20.88, 25.43 ± 20, shown in Fig. 4.

In another aspect, the present invention provides a novel process for the preparation of novel crystalline Dexlansoprazole Form IV comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent, isolating followed by aerial drying to get crystalline Dexlansoprazole Form IV.

In one aspect the present invention provides a novel crystalline form of Dexlansoprazole designated as Form V, having an X-ray diffraction pattern with peaks at 10.66, 13.223, 13.72, 15.93, 21.46, 24.41, 25.91, 27.99 ± 20, shown in Fig. 5.

In another aspect, the present invention provides a process for the preparation of crystalline Dexlansoprazole Form V comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent, isolating followed by aerial drying to get crystalline Dexlansoprazole Form V.

In one aspect the present invention provides a novel crystalline form of Dexlansoprazole designated as Form VI, having an X-ray diffraction pattern with peaks at 5,39, 17.75, 22,79, 25.60, ± 26, shown in Fig. 6.

In another aspect, the present invention provides a novel process for the preparation of novel crystalline Dexlansoprazole Form VI comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent, isolating novel crystalline Dexlansoprazole Form VI.

In another aspect, the present invention provides a novel crystalline tartrate salt of Dexlansoprazole, having an X-ray diffraction pattern with peaks at 3,4, 5,9, 10,2, 12,5, 15.6, 19.3, 19.7, 21.1, 22.0, 23.0 ± 29, shown in Fig, 7.

In another aspect, the present invention provides a process for preparing crystalline tartrate salt of Dexlansoprazole comprising the steps of; dissolving Dexlansoprazole and L-tartaric acid in a solvent, stirring the solution at room temperature to afford Dexlansoprazole L-Tartrate salt.

In another aspect, the present invention provides a novel process for the preparation of amorphous form of Dexlansoprazole comprising the steps of; dissolving Dexlansoprazole in a solvent and removing the solvent to afford amorphous Dexlansoprazole.

In another aspect, the present invention provides a novel process for the preparation of amorphous Dexlansoprazole comprising the steps of; a) dissolving Dexlansoprazole in a solvent, b) adding antisolvent, c) isolating amorphous Dexlansoprazole,

In another aspect, the present invention provides a novel process for the preparation of amorphous Dexlansoprazole wherein grinding Dexlansoprazole in mortar and pestle for several hours at room temperature to afford amorphous form of Dexlansoprazole.

In another aspect, the present invention provides a novel process for the preparation of amorphous Dexlansoprazole, which comprising the steps of; heating Dexlansoprazole Form I, II or III under reduced pressure to get amorphous Dexlansoprazole.

In another aspect, the amorphous Dexlansoprazole disclosed in the present invention is confirmed by PXRD pattern shown in Fig. 8.

In another aspect, the present invention provides a novel process for the preparation of anhydrous crystalline Dexlansoprazole comprising the steps of; a) dissolving Dexlansoprazole in a solvent b) adding antisolvent and c) isolating the anhydrous crystalline Dexlansoprazole.

In another aspect the present invention provides a novel process for the preparation of crystalline Dexlansoprazole sesquihydrate comprising the steps of; a) dissolving Dexlansoprazole in a solvent b) adding antisolvent and c) isolating the crystalline Dexlansoprazole sesquihydrate.

In another aspect, the present invention provides a novel process for the preparation of crystalline Dexlansoprazole sesquihydrate comprising the steps of; dissolving Dexlansoprazole in acetone and subjected to acid base treatment to afford crystalline Dexlansoprazole sesquihydrate,

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a representative X-ray diffraction pattern of crystalline Dexlansoprazole Form I

FIG. 2 is a representative X-ray diffraction pattern of crystalline Dexlansoprazole Form
II

FIG. 3 is a representative X-ray diffraction pattern of crystalline Dexlansoprazole Form
III

FIG. 4 is a representative X-ray diffraction pattern of crystalline Dexlansoprazole Form
IV

FIG. 5 is a representative X-ray diffraction pattern of crystalline Dexlansoprazole Form
V

FIG. 6 is a representative X-ray diffraction pattern of crystalline Dexlansoprazole Form
VI

FIG. 7 is a representative X-ray diffraction pattern of crystalline tartrate salt of
Dexlansoprazole

FIG. 8 is a representative X-ray diffraction pattern of amorphous Dexlansoprazole

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to novel polymorphic forms of Dexlansoprazole designated as Form I, J1, HI, IV, V and VI and processes for the preparation of the said polymorphic forms I, II? III, IV, V and VI.

The present invention also relates to novel tartrate salt of Dexlansoprazole and process for the preparation thereof.

The present invention further relates to novel processes for the preparation of amorphous, crystalline anhydrous and sesquihydrate of Dexlansoprazole.

In one embodiment, the present invention provides a novel crystalline form of Dexlansoprazole designated as Form I, having an X-ray diffraction pattern with peaks at 9.15,9.71, 10.39, 11.25, 13.12, 13.71, 19.47, 20.86 ± 26, shown in Fig 1.

In another embodiment, the present invention provides a novel crystalline form of
Dexlansoprazole designated as Form II, having an X-ray diffraction pattern with peaks
at 8.53, 9.02, 10.14, 11.36, 11.91, 13.79, 16.88, 19.42, 21.96, 23.98 ± 20, shown in Fig.
2.

In another embodiment, the present invention provides a novel crystalline
Dexlansoprazole Form III, having an X-ray diffraction pattern with peaks at 6.66,
14.33, 18.69, ± 29, shown in Fig. 3.

In another embodiment, the present invention provides a novel crystalline Dex lansoprazole Form IV, having an X-ray diffraction pattern with peaks at 5.89, 17.73, 19.40, 20.32, 20.88, 25.43 ± 20, shown in Fig. 4.

In another embodiment, the present invention provides a novel crystalline Dexlansoprazole Form V, having an X-ray diffraction pattern with peaks at 10.66, 13.223, 13.72, 15.93, 21.46, 24.41, 25.91, 27.99 ± 29, shown in Fig. 5.

In another embodiment, the present invention provides a novel crystalline Dexlansoprazole Form VI, having an X-ray diffraction pattern with peaks at 5.39, 17,75, 22.79, 25.60 ± 29, shown in Fig. 6,

In another embodiment, the present invention provides a process for the preparation of crystalline Dexlansoprazole Form I, which comprising the steps of; dissolving Dexlansoprazole in solvent, adding water and/or antisolvent and isolating crystalline Dexlansoprazole Form I.

According to the present invention, Dexlansoprazole is dissolved in a solvent selected from methanol, ethanol, isopropanol or butanol, added water, followed by adding an antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and filtered the obtained solid to get crystalline Dexlansoprazole Form I.

In another embodiment, the present invention provides a process for the preparation of crystalline Dex lansoprazole Form II comprising the steps of; dissolving Dexlansoprazole in solvent, seeding with Form II, adding water and/or antisolvent and isolating crystalline Dexlansoprazole Form II.

According to the present invention, Dexlansoprazole is dissolved in a solvent selected from methanol, ethanol, isopropanol or butanol, seeded the reaction mass with Dexlansoprazole Form II, added water and optionally antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and filtered the obtained solid to get crystalline Dexlansoprazole Form II.

In another embodiment, the present invention provides a process for the preparation of crystalline Dexlansoprazole Form III comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent and aerial drying to get Dexlansoprazole Form III.

According to the present invention, Dexlansoprazole is dissolved in solvent selected from methanol, ethanol, isopropanol or butanol, added an antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and filtered the obtained solid to get crystalline Dexlansoprazole Form III.

In another embodiment, the present invention provides a novel process for the preparation of novel crystalline Dexlansoprazole Form IV comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent and stirring, isolating followed by aerial drying to get crystalline Dexlansoprazole Form IV.

According to the present invention, Dexlansoprazole is dissolved in isopropanol, added antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and filtered the obtained solid to get crystalline Dexlansoprazole Form-IV.

In another embodiment, the present invention provides a process for the preparation of crystalline Dex lansoprazole Form V comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent and stirring, isolating followed by aerial drying to get crystalline Dexlansoprazole Form V.

According to the present invention, Dexlansoprazole is dissolved in pyridine, added antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and filtered the obtained solid to get crystalline Dexlansoprazole Form V.

In another embodiment, the present invention provides a novel process for the preparation of novel crystalline Dexlansoprazole Form VI comprising the steps of; dissolving Dexlansoprazole in solvent, adding an antisolvent and stirring, isolating novel crystalline Dexlansoprazole Form VI.

According to the present invention, Dexlansoprazole is dissolved in n-propanol, added antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and filtered the obtained solid to get crystalline Dexlansoprazole Form VI.

In another embodiment, the present invention provides a process for preparing crystalline tartrate salt of Dexlansoprazole comprising the steps of; dissolving Dexlansoprazole and L-tartaric acid in a solvent, stirring the solution at room temperature to afford Dexlansoprazole L-Tartrate salt.

According to the present invention, Dexlansoprazole and L-tartaric acid are dissolved in solvent selected from ketones such as methyl ethyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, ethers such as t-butyl methyl ether, optionally adding an antisolvent selected from diisopropyl ether, diethyl ether and hydrocarbons such as n-pentane, n-hexane, n-heptane, cyclohexane, octane or mixtures thereof and filtered the obtained solid to get tartrate salt of Dexlansoprazole.

In another embodiment the novel crystalline tartrate salt of Dexlansoprazole is confirmed by PXRD pattern as shown in Fig. 7.

The tartrate salt of Dex lansoprazole prepared according to the present invention has an X-ray diffraction pattern with peaks at 3,4, 5-9, 10.2, 12.5, 15.6, 19.3, 19.7, 21.1, 22.0, 23.0 ±26.

In another embodiment, the present invention provides a novel process for the preparation of amorphous form of Dexlansoprazole comprising the steps of; dissolving Dexlansoprazole in a solvent and removing the solvent to afford amorphous Dexlansoprazole.

In another embodiment, the present invention provides a novel process for the preparation of amorphous Dexlansoprazole comprising the steps of; a) dissolving Dexlansoprazole in a solvent, b) adding an antisolvent, c) isolating amorphous Dexlansoprazole,

According to the present invention, Dexlansoprazole is dissolved in solvent selected from ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone halogenated hydrocarbons such as dichloromethane, dichloroethane, trichloromethane alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, esters such as alkyl esters like methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate and nitriles such as acetonitrile or mixtures thereof, optionally adding an antisolvent selected from diisopropyl ether, diethyl ether and hydrocarbons such as n-pentane, n-hexane, n-heptane, cyclohexane, octane or mixtures thereof, removing the solvent by using conventional methods such as distillation, spray drying, freeze drying or agitated thin film dryer (ATFD) to get amorphous Dexlansoprazole.

In another embodiment, the present invention provides a novel process for the preparation of amorphous Dexlansoprazole wherein grinding Dexlansoprazole in mortar and pestle for several hours at room temperature to afford amorphous form of Dexlansoprazole

In another embodiment, the present invention provides a novel process for the preparation of amorphous Dexlansoprazole, which comprising the steps of; heating Dexlansoprazole Form I, II or III under reduced pressure to get amorphous Dexlansoprazole.

According to the present invention, Dexlansoprazole Form I, II or III are dried under vacuum at about 20-40°C to get amorphous Dexlansoprazole.

In another embodiment, the amorphous form of Dexlansoprazole disclosed in the present invention is confirmed by PXRD pattern as shown in Fig. 8.

In another embodiment, the present invention provides a novel process for the preparation of anhydrous crystalline Dexlansoprazole comprising the steps of; a) dissolving Dexlansoprazole in a solvent b) adding antisolvent and c) isolating the anhydrous crystalline Dexlansoprazole.

According to the present invention, Dexlansoprazole is dissolved in a solvent selected from ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone, halogenated hydrocarbons such as dichloromethane, dichloroethane, trichIoromethane, added an antisolvent such as methyl t-butyl ether, diisopropyl ether, diethyl ether, hydrocarbons such as n-hexane, n-heptane, cyclohexane, methyl cyclohexane, toluene or mixture thereof and filtered the obtained solid to get anhydrous crystalline Dexlansoprazole.

In another embodiment the present invention provides a novel process for the preparation of crystalline Dexlansoprazole sesquihydrate comprising the steps of; a) dissolving Dexlansoprazole in a solvent b) adding antisolvent and c) isolating the crystalline Dexlansoprazole sesquihydrate.

According to the present invention, Dexlansoprazole is dissolved in a solvent selected from acetonitrile, acetone, l-methyl-2-pyrrolidine, KN-dimethyl formamide, dioxane, dichloromethane, ethyl acetate, added antisolvent selected from water, n-pentane, n-hexane, heptane, cyclohexane, methyl cyclohexane, toluene, diisopropyl ether, methyl t-butyl ether, diethyl ether or mixtures thereof and filtered the obtained solid to get crystalline Dexlansoprazole sesquihydrate by filtering,

In another embodiment, the present invention provides a novel process for the preparation of crystalline Dexlansoprazole sesquihydrate comprising the steps of; dissolving Dexlansoprazole in acetone and subjected to acid base treatment to afford crystalline Dexlansoprazole sesquihydrate.

According to the present invention, Dexlansoprazole is dissolved in acetone at room temperature, pH is adjusted using 10% aqueous hydrochloric acid, stirred for 30-40 mm followed by treating with 10% sodium hydroxide solution, diluted with water and the obtained solid is filtered to get crystalline Dexlansoprazole sesquihydrate.

According to the present invention, starting material used herein for the preparation of Dexlansoprazole Form I, II, III, IV, V, VI, amorphous, anhydrous, sesquihydrate may be amorphous, anhydrous or hydrous Dexlansoprazole.

The following examples are provided for illustrative purposes only and are not intended to limit the scope of the invention in any way.

EXPERIMENTAL SECTION

Powder X-ray Diffraction (PXRD)
The X-ray diffraction patterns of said polymorphs of the invention were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of 8/6 configuration and X'Celerator detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 26 range of 2.0°-50.0°, 0.030° step size and 50 seconds step time.

Example 1: Preparation of Dexlansoprazole Form I
Ig of Dexlansoprazole is dissolved in 5 ml ethanol and stirred for 15 minutes at 0-5°C. Water (I ml) is added and stirred for 0.5 h at 0-5°C. To the thick gummy mass obtained, IPE (50 ml) is added and stirred for 2h at 5-10°C. The solid obtained is filtered and washed with IPE and dried at ambient conditions. The solid obtained is identified as novel crystalline Dexlansoprazole Form I.

Example 2: Preparation of Dexlansoprazole Form II by seeding 0.5g of Dexlansoprazole is dissolved in 5 ml ethanol and stirred for 15 minutes at 0-5°C. To this clear solution seeds of Form II were added, added water (1 ml) and stirred for 0.5 h at 0-5°C. To the thick gummy mass obtained, IPE (50 ml) is added and stirred for 2h at 5-10°C. The solid obtained is filtered and washed with IPE and dried at ambient conditions. The solid obtained is identified as novel crystalline Dexlansoprazole Form II,

Example 3: Preparation of Dexlansoprazole Form III

lg of Dexlansoprazole was dissolved in ethanol (5 ml) at 25-30QC. The clear solution was added to heptane (50 ml) and maintained for 30-60 min at 25-30°C with agitation.

The solid obtained was filtered and aerially dried at room temperature. The product obtained was identified as Dexlansoprazole Form III

Example 4: Preparation of Dexlansoprazole Form III
0.5g of Dexlansoprazole is dissolved in ethanol (5 ml) and stirred for 15 minutes at 25-30°C. Cool the solution to -30°C, added heptane (20 ml) and stirred for 0.5 h at -30°C. Slowly raise the temperature to room temperature and add heptane (5ml) at 25-30°C and stirred for 15-30 minutes. The resulting precipitate was further cooled to -10°C and stir for 30 minutes. The solid obtained is filtered and washed with heptane (1ml). The solid obtained is identified as novel crystalline Dexlansoprazole Form HI.

Examples S: Preparation of Dexlansoprazole Form IV
lg of Dexlansoprazole was dissolved in isopropyl alcohol (5 ml) at 25-30°C. The clear solution was added to heptane (50 ml) and maintained for 30-60 min at 25-30°C. The solid obtained was filtered and aerially dried. The product was identified as Dexlansoprazole Form IV

Examples 6: Preparation of Dexlansoprazole Form V 3g of Dexlansoprazole was suspended in pyridine (12 ml) at 25-30DC and stirred for 15-20 min to get the clear solution. To this solution heptane (100 ml) added dropwise and maintained for 30-60 min at 25-30aC with agitation. The solid obtained was filtered and washed with heptane (50 ml). The product obtained was identified as Dexlansoprazole Form V.

Example 7: Preparation of Dexlansoprazole Form VI 0.5g Dexlansoprazole was dissolved in n-Propanol (3 ml) at 25-30°C, To the clear solution n-Heptane (20 ml) was added at 25-30°C and stirred for 1-3 hrs at 25-30°C. The solid obtained was filtered, washed with n-Heptane (10 ml) and dried at ambient temperature. The product obtained was identified as Dexlansoprazole Form VI.

Example 8; Preparation of amorphous Dexlansoprazole from Dexlansoprazole Form I
by heating 0.5g of Dexlansoprazole Form I obtained as described above was kept in oven at 40°C under vacuum for lhr. The resulting solid was identified as amorphous Dexlansoprazole.

Example 9: Preparation of Dexlansoprazole amorphous from Dexlansoprazole Form II
by heating 0,5g of Dexlansoprazole Form II obtained as described above was kept in oven at 40°C under vacuum for The resulting solid was identified as amorphous
Dexlansoprazole.

Example 10: Preparation of Dexlansoprazole amorphous from Dexlansoprazole Form III by heating 0.5g of Dexlansoprazole Form III obtained as described above was kept in oven at 40°C under vacuum for 2-3hr. The resulting solid was identified as amorphous Dexlansoprazole.

Example 11: Preparation of amorphous Dexlansoprazole lg of Dexlansoprazole was dissolved in acetone (10 ml) at 25 to 30°C. The clear solution was then subjected to distillation to remove the solvent completely under vacuum at 35°C, The solid isolated was identified as amorphous Dexlansoprazole.

Example 12: Preparation of amorphous Dexlansoprazole
0.5g of Dexlansoprazole was dissolved in dichloromethane (5 ml) at 25 to 30°C. The clear solution was then subjected to distillation to remove the solvent completely under vacuum at 35°C. The solid isolated was identified as amorphous Dexlansoprazole.

Example 13; Preparation of amorphous Dexlansoprazole
0.5g of Dexlansoprazole was dissolved in methanol (5 ml) at 25 to 30°C, The clear solution was then subjected to distillation to remove the solvent completely under vacuum at 35°C. The solid isolated was identified as amorphous Dexlansoprazole.

Example 14: Preparation of amorphous Dexlansoprazole
0.5g of Dexlansoprazole was dissolved in ethyl acetate (5 ml) at 25 to 30°C. The clear solution was then subjected to distillation to remove the solvent completely under vacuum at 35°C. The solid isolated was identified as amorphous Dexlansoprazole.

Example 15: Preparation of amorphous Dexlansoprazole
1 g of Dexlansoprazole was dissolved in acetonitrile (10 ml) at 25 to 30°C The clear solution was then subjected to distillation to remove the solvent completely under vacuum at 35°C. The solid isolated was identified as amorphous Dexlansoprazole,

Example 16: Preparation of amorphous Dexlansoprazole
0.5 g Dexlansoprazole was dissolved in n-Propanol (2 ml) at 25-30°C. To the clear solution n-Pentane (20 ml) was added at 25-30°C and stirred for 1-3 hrs at 25-30°C. The solid obtained was filtered, washed with n-Pentane (10 ml) and dried at ambient temperature. The product obtained was identified as amorphous Dexlansoprazole.

Example 17: Preparation of amorphous Dexlansoprazole by Spray-drying
5g of Dexlansoprazole was suspended in dichloromethane (100 ml) at room
temperature. The resulting solution was filtered through hyflow to remove any undissolved particulate. The filtered solution was then subjected to spray drying in a Mini Spray Dryer (Model Buchi - 290). The obtained solid was identified as amorphous Dex lansoprazole.

Example 18: Preparation of amorphous Dexlansoprazole by Spray-drying 5g of Dexlansoprazole was suspended in acetone (100 ml) at room temperature. The resulting solution was filtered through hyflow to remove any undissolved particulate. The filtered solution was then subjected to spray drying in a Mini Spray Dryer (Model Buchi - 290). The obtained solid was identified as amorphous Dexlansoprazole.

Example 19: Preparation of amorphous Dexlansoprazole by Spray-drying 5g of Dexlansoprazole was suspended in ethanol (50 ml) at room temperature. The resulting solution was filtered through hyflow to remove any undissolved particulate. The filtered solution was then subjected to spray drying in a Mini Spray Dryer (Model Buchi - 290). The obtained solid was identified as amorphous Dexlansoprazole.

Example 20: Preparation of amorphous Dexlansoprazole by Spray-drying 5g of Dexlansoprazole was suspended in isopropanol (50 ml) at room temperature. The resulting solution was filtered through hyflow to remove any undissolved particulate. The filtered solution was then subjected to spray drying in a Mini Spray Dryer (Model Buchi - 290). The obtained solid was identified as amorphous Dexlansoprazole.

Example 21: Preparation of amorphous Dexlansoprazole by Grinding
0.5g of Dexlansoprazole was ground in a mortar for 15 to 30 minutes at room
temperature. The solid resulted was identified as amorphous Dexlansoprazole.

Example 22: Preparation of anhydrous crystalline Dexlansoprazole
lg Dexlansoprazole was dissolved in acetone (5 ml) at 25 to 30°C. To the resulting clear
solution isopropyl ether (80 ml) was added slowly at 25 to 30°C and stirred for 1 hour.

The solid obtained was filtered, washed with chilled isopropyl ether (20 ml) and dried at ambient temperature. The product obtained was identified as crystalline anhydrous Dex lansoprazole.

Example 23: Preparation of anhydrous crystalline Dexlansoprazole
0.5g Dexlansoprazole was dissolved in dichloromethane (2 ml) at 25 to 30°C. To the resulting clear solution heptane (10 ml) was added slowly at 25 to 30°C and stirred for 1 hour. The solid obtained was filtered, washed with heptane (10 ml) and dried at ambient temperature. The product obtained is identified as crystalline anhydrous Dexlansoprazole.

Example 24: Preparation of anhydrous crystalline Dexlansoprazole
0.5g of Dexlansoprazole was suspended in appropriate solvents in appropriate volumes at 25 to -30°C and stirred for 2 hours. The resulting solid was filtered and was analyzed by X-Ray Powder Diffraction. The results obtained are displayed in Table 1.

Example 25: Preparation of anhydrous crystalline Dexlansoprazole 0.2g of Dexlansoprazole was suspended in appropriate solvents (5 ml) at 25 to 30°C and stirred for 2 hours. The resulting solid was filtered and was analyzed by X-Ray Powder Diffraction. The results obtained are displayed in Table 2.


Example 26: Preparation of crystalline Dexlansoprazole Sesquihydrate
0.5g Dexlansoprazole was dissolved in acetonitrile (5 ml) at 25 to 30°C. To the resulting
clear solution water (25 ml) was added slowly at 25 to 30°C and stirred for 1 hour. The
solid obtained was filtered, washed with water (10 ml) and dried at ambient
temperature. The product obtained was identified as crystalline Dexlansoprazole
sesquihydrate.

Example 27: Preparation of crystalline Dexlansoprazole Sesquihydrate 0.5g Dexlansoprazole is dissolved in acetone (5 ml) at 25 to 30°C. To the resulting clear solution water (25 ml) was added slowly at 25 to 30°C and stirred for 1 hour. The solid obtained was filtered, washed with water (10 ml) and dried at ambient temperature. The product obtained was identified as crystalline Dexlansoprazole sesquihydrate.

Example 28; Preparation of crystalline Dexlansoprazole Sesquihydrate 0.5g Dexlansoprazole was dissolved in l-methyl-2-pyrrolidinone (5 ml) at 25 to 30°C.

To the resulting clear solution water (25 ml) was added slowly at 25 to 30°C and stirred
for 1 hour. The solid obtained was filtered, washed with water (10 ml) and dried at ambient temperature. The product obtained is identified as crystalline D ex lansoprazole sesquihydrate.

Example 29: Preparation of crystalline Dexlansoprazole Sesquihydrate
0.5g Dexlansoprazole was dissolved in N, N-Dimethyl formamide (5 ml) at 25 to 30°C.

To the resulting clear solution water (25 ml) was added slowly at 25 to 30°C and stirred
for 1 hour. The solid obtained was filtered, washed with water (10 ml) and dried at
ambient temperature. The product obtained is identified as crystalline Dexlansoprazole
sesquihydrate.

Example 30: Preparation of crystalline Dexlansoprazole Sesquihydrate
0.5g Dexlansoprazole was dissolved in dioxane (5 ml) at 25 to 30°C. To the resulting
clear solution n-hexane (25 ml) was added slowly at 25 to 30°C and stirred for 1 hour.

The solid obtained was filtered, washed with n-hexane (10 ml) and dried at ambient
temperature. The product obtained was identified as crystalline Dexlansoprazole
sesquihydrate.

Example 31: Preparation of crystalline Dexlansoprazole Sesquihydrate 0.5g Dexlansoprazole was dissolved in dichloromethane (5 ml) at 25 to 30°C. To the resulting clear solution isopropyl ether (20 ml) was added slowly at 25 to 30°C and stirred for 1 hour. The solid obtained was filtered, washed with isopropyl ether (10 ml) and dried at ambient temperature. The product obtained was identified as crystalline Dexlansoprazole sesquihydrate.

Example 32: Preparation of crystalline Dexlansoprazole Sesquihydrate 0,5g Dexlansoprazole was dissolved in ethyl acetate (5 ml) at 25 to 30°C. To the resulting clear solution n-heptane (15 ml) was added slowly at 25 to 30°C and stirred for 1 hour.

The solid obtained was filtered, washed with n-heptane (10 ml) and dried at ambient temperature. The product obtained was identified as crystalline
Dexlansoprazole sesquihydrate.

Example 33: Preparation of crystalline Dexlansoprazole Sesquihydrate 0.5g Dexlansoprazole was dissolved in acetone (5 ml) at 25 to 30°C and pH of the solution was slowly adjusted to acidic (pH 4) by addition of 10% HC1 (0.5 ml) and stirred for 0.5 hours. The solution was then neutralized by addition of 10% NaOH followed by addition of 20 ml of water at 25-30°C. The solid obtained was filtered, washed with water (10 ml) and dried at ambient temperature. The product obtained was identified as crystalline
Dexlansoprazole sesquihydrate.

Example 34: Preparation of crystalline Dexlansoprazole sesquihydrate 0.5g of Dexlansoprazole was suspended in water (10 ml) at 25-30°C and stirred for 1-2 hours.

The resulting solid was filtered and dried at ambient temperature. The resulting solid was filtered and was analyzed by X-Ray Powder Diffraction. The results obtained are displayed in Table 3.


Example 35: Preparation of crystalline Dexlansoprazole sesquihydrate
0.5g of Dexlansoprazole was exposed to relative humidity > 90% in a dessicator for different time intervals. The resulting solid was filtered and was analyzed by X-Ray Powder Diffraction. The results obtained are displayed in Table 4.

Example 36: Preparation of Dexlansoprazole L-Tartrate salt
0.8g L-Tartaric acid and Dexlansoprazole (2g) are dissolved in acetone (20 ml) at 25 to 30°C. The clear solution is then stirred for 1 hour at 25 to 30°C. The solid obtained is filtered, washed with acetone and dried at ambient temperature. The solid obtained is identified as Dexlansoprazole L-Tartrate salt.

Example 37: Preparation of Dexlansoprazole L-Tartarate salt 0.8g L-Tartaric acid and Dexlansoprazole (2 g) are dissolved in acetone (25 ml) at 25-30°C. The clear solution is then stirred for 1 hour at 25-30°C. IPE (100 ml) was added to the above solution slowly at 25-30°C and stirred for 2 hours. The solid obtained was filtered, washed with IPE (10 ml) and dried at ambient temperature. The product obtained was identified as crystalline Dexlansoprazole L-Tartarate salt.

We Claim:

1. A process for the preparation of novel crystalline Dexlansoprazole Form I, which comprises dissolving Dexlansoprazole in an organic solvent selected from methanol, ethanol, isopropanol or butanol, adding water and/or antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and isolating crystalline Dexlansoprazole Form-I,

2. A process for the preparation of novel crystalline Dexlansoprazole Form II, which comprises dissolving Dexlansoprazole in an organic solvent selected from methanol, ethanol, isopropanol or butanol, seeding with Dexlansoprazole Form-I I adding water and/or antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and isolating crystalline Dexlansoprazole Form-II.

3. A process for the preparation of novel crystalline Dexlansoprazole Form III, which comprises dissolving Dexlansoprazole in an organic solvent selected from methanol, ethanol, isopropanol or butanol, adding antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and isolating crystalline Dexlansoprazole Form-Ill.

4. A process for the preparation of novel crystalline Dexlansoprazole Form IV, which comprises dissolving Dexlansoprazole in isopropyl alcohol, adding antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and isolating crystalline Dexlansoprazole Form-IV,

5. A process for the preparation of novel crystalline Dexlansoprazole Form V, which comprises dissolving Dexlansoprazole in pyridine, adding antisolvent such as isopropyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and isolating crystalline Dexlansoprazole Form-V.

6. A process for the preparation of crystalline Dexlansoprazole Form VI, which comprises dissolving Dexlansoprazole in n-propanol, adding antisolvent such as isopropyl ether, n-pentane, n-hexane, n-hcptane and isolating crystalline Dexlansoprazole Form-VL

7. A process for the preparation of amorphous Dexlansoprazole, which comprises dissolving Dexlansoprazole in an organic solvent selected from acetone, dichloromethane, methanol, ethanol, isopropyl alcohol, ethyl acetate, acetonitrile removing the solvent by using techniques such as distillation, spray drying, freeze drying, agitated thin film dryer (ATFD) and isolating amorphous Dexlansoprazole.

8. A process for the preparation of amorphous Dexlansoprazole, which comprises dissolving Dexlansoprazole in n-propanol, adding antisolvent such as n-pentane, n-hexane, n-heptane or cyclohexane followed by isolating the solid and drying to get amorphous Dexlansoprazole.

9. A process for the preparation of amorphous Dexlansoprazole, which comprises heating Dexlansoprazole Form I, II or III under reduced pressure to get amorphous Dexlansoprazole.

10. A process for the preparation of anhydrous crystalline Dexlansoprazole, which comprises dissolving Dexlansoprazole in acetone, dichloromethane, dichloroethane, adding antisolvent selected from diisopropyl ether, diethyl ether, n-pentane, n-hexane, n-heptane or cyclohexane and isolating anhydrous crystalline Dexlansoprazole.

11. A process for the preparation of anhydrous crystalline Dexlansoprazole, which comprises, slurring Dexlansoprazole Form III, IV or V in a solvent selected from n-heptane, n-hexane, n-heptane, cyclohexane isopropyl ether or toluene and isolating anhydrous crystalline Dexlansoprazole.

12. A process for the preparation of crystalline Dexlansoprazole sesquihydrate, which comprises slurring Dexlansoprazole Form III, IV, V, VI or amorphous in water and isolating crystalline Dexlansoprazole sesquihydrate.

13. A process for the preparation of crystalline Dexlansoprazole sesquihydrate, which comprises dissolving Dexlansoprazole in an organic solvent selected from acetonitrile, acetone, l-methylpyrrolidine, dimethylformamide, dioxane, dichloromethane, ethylacetate, adding antisolvent selected from water, n-pentane, n-hexane, n-heptane, n-pentane, cyclohexane, isopropyl ether and isolating crystalline Dexlansoprazole sesquihydrate.

14. A process for the preparation of crystalline Dexlansoprazole sesquihydrate, which comprises dissolving Dexlansoprazole in an organic solvent selected from acetone, acetonitrile, dioxane, treating with an acid followed by base and isolating crystalline Dexlansoprazole sesquihydrate.

15. The process according to claim 14, wherein the acid is selected from 10% aqueous hydrochloride and the base is 10% aqueous sodium hydroxide.

16. A process for the preparation of crystalline tartrate salt of Dexlansoprazole, which comprises dissolving Dexlansoprazole and L-tartaric acid in acetone, acetonitrile or dioxane; optionally adding an antisolvent selected from n-pentane, n-hexane, n-heptane, cyclohexane or isopropyl ether and isolating Dexlansoprazole L-tartrate salt.