ESOMEPRAZOLE SALTS AND PROCESSES FOR PREPARATION THEREOF
INTRODUCTION TO THE INVENTION
The present invention relates to the esomeprazole salts and processes for preparation thereof. It also relates to polymorphic forms of esomeprazole salts.
Esomeprazole has a chemical name (S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-ethyl]sulfinyl]-1H-benzimidazole (hereinafter referred to by the adopted name "esomerprazole"), is the S-enantiomer of omeprazole, and has the structure of Formula I.

Esomeprazole is a proton pump inhibitor developed as an oral treatment for peptic ulcer, gastroesophangeal reflux disease (GERD), duodenal ulcer and esophagitis.
Esomeprazole magnesium is available in the market under the brand name NEXIUM™ as delayed-release capsules for oral administration. Each delayed release capsule contains 20 mg or 40 mg esomeprazole (present as 22.3 mg or 44.5 mg of esomeprazole magnesium trihydrate) in the form of enteric-coated pellets. Esomeprazole sodium is also available as a sterile, freeze dried, white to off white, porous cake or powder in a 5 mL vial, intended for intravenous administration after reconstitution; NEXIUM I.V. injection contains esomeprazole sodium 21.3 mg of 42.5 mg equivalent to esomeprazole 20 mg or 40 mg.
U.S. Patent No. 6,143,771 discloses esomeprazole sodium and processes for its preparation.
U.S. Patent No. 6,875,872 discloses esomeprazole magnesium and a process for its preparation.

International Application Publication No. WO 2003/089408 discloses alkali or alkaline earth metal salts of esomepazole, including a sodium salt.
International Application Publication No. WO 1998/54171 discloses a process for the preparation of the magnesium salt of the S-enantiomer of omeprazole trihydrate, wherein a potassium salt of S-omeprazole is used as an intermediate.
There is a general need for pharmaceutical^ active compounds that can be produced by processes giving products suitable for pharmaceutical preparations. Such products have the following properties: easy to handle, good dissolution rate, excellent bioavailability and good storage stability. It has been observed that many of the crystalline forms of esomeprazole or its pharmaceutical^ acceptable salts as well as its amorphous form are unstable under normal storage conditions and this results in significantly increased impurities in the product over time.
Although the known esomeprazole salts and their polymorphic forms address some of the deficiencies in terms of formulated product manufacturability, there remains a need for yet further improvement in these properties as well as improvements in other properties such as flowability, vapor impermeability and solubility. Further, the discovery of new crystalline polymorphic forms of a drug enlarges the repertoire of materials that a formulation scientist has with which to design a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristics.
Pharmaceutical stability depends on simultaneous influence of a variety of factors, of which some important factors are the size of crystals, shape of crystals, water assay, assay of residual solvents and assay of impurities, one or more of these factors can be uniquely characterized by the isolation process of the crystalline forms of esomeprazole salts according to the invention.
Toward this end, it has been the endeavour of pharmaceutical scientists to provide a novel and stable crystalline form of drug substances, more specifically, thermodynamically stable forms of drug substances, which would have the strengths of the crystalline forms, viz. thermodynamic stability, and those of the

amorphous form, wz. enhanced solubility, rapid onset of action and an enhanced bioavailability.
There is thus a need to provide salts and their polymorphs of esomeprazole and processes for their preparation, which are inexpensive, readily scaleable to industrial levels.
SUMMARY OF THE INVENTION
Aspects of the present invention relate to the esomeprazole salts and processes for preparation thereof. Embodiments of the invention also relate to polymorphic forms of esomeprazole salts such as calcium, lithium, potassium, barium, zinc, and copper salts, and the like.
In one aspect, the present invention provides a process for the preparation of esomeprazole salts, which process comprises:
1) providing a solution comprising esomeprazole in a suitable organic solvent under suitable conditions;
2) adding a suitable base to the solution of step 1) under suitable conditions;
3) recovering a solid from step 2) under suitable conditions to afford the desired salt of esomeprazole.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole copper salt designated herein as Form C1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 22.6, 23.5, 25.5, 31.8, 33.9, and 37.8, ± 0.2 degrees 2 theta. Form C1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 1.
In yet another aspect, the present invention provides a crystalline polymorph of an esomeprazole copper salt designated herein as Form C2, characterized by X-ray powder diffraction pattern with characteristic peaks at approximately 18.6,19.0, 22.6, and 37.8, ± 0.2 degrees 2 theta. Form C2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 2.

In another aspect, the present invention provides an amorphous form of an esomeprazole copper salt, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 3.
In a further aspect, the present invention provides an amorphous form of an esomeprazole zinc salt, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 4.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole zinc salt designated herein as Form Z1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 27.2 and 31.6, ± 0.2 degrees 2 theta. Form Z1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 5.
In a still further aspect, the present invention provides an amorphous form of an esomeprazole zinc salt characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 6.
In another aspect, the present invention provides an amorphous form of an esomeprazole barium salt characterized by an X-ray powder diffraction pattern, substantially in accordance with Fig. 7.
In an aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 16.0, 16.2, and 24.3, ± 0.2 degrees 2 theta. Form B1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 8.
In an aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 26.0, 16.2,21.1,27.3,27.3, 39.2 and 40.5, ± 0.2 degrees 2 theta. Form B2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 9.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately

5.4, 6.4, 15.9, 16.2, 17.8, 24.3, 24.3, 26.0, and 28.1, ± 0.2 degrees 2 theta. Form
B3 is also characterized by an X-ray powder diffraction pattern substantially in
accordance with Fig. 10.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.7, 13.4, 16.0, 16.3, 21.2, 24.4, 23.8, and 27.3, ± 0.2 degrees 2 theta. Form B4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 11.
In an aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B5, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 13.3,15.9, 16.2, 24.7, 26.0, and 27.2, ± 0.2 degrees 2 theta. Form B5 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 12.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B6, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately
5.5, 6.9, 13.4, 15.9, 16.2, 21.2, 24.8, and 27.2, ± 0.2 degrees 2 theta. Form B6 is
also characterized by an X-ray powder diffraction pattern substantially in
accordance with Fig. 13.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 6.3, 16.2, 18.5, 23.7, 24.6,25.1, and 27.8, ± 0.2 degrees 2 theta. Form P1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 14.
In a further aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.0, 17.5, 18.8, 22.5, 22.8, 28.7, 29.2, 33.6, 35.4, 35.6, and 36.2, ± 0.2 degrees 2

theta. Form P2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 15.
In a still further aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.5, 14.3, 18.3, 18.9, 19.9, 21.3, 22.4, 22.9, 25.8, and 31.1, ±0.2 degrees 2 theta. Form P3 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 16.
In a yet further aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.5, 14.3, 18.3, 18.9, 19.9, 21.3, 22.4, 22.9, 25.8, and 31.13, ± 0.2 degrees 2 theta. Form P4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 17.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P5, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.5, 14.9, 18.9, 19.9, and 22.9, ± 0.2 degrees 2 theta. Form P5 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 18.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P6, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.4, 18.2, 21.3, 23.0, and 31.02, ± 0.2 degrees 2 theta. Form P6 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 19.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P7, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.2, 7.2, 18.1, 18.9, and 22.8, ± 0.2 degrees 2 theta. Form P7 is also

characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 20.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.4, 11.4( 13.0, and 24.2, ± 0.2 degrees 2 theta. Form K1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 21.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 6.4, 6.7, 26.1, and 31.6, ± 0.2 degrees 2 theta. Form K2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 22.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.9, 6.2, 8.8, 9.3, 14.6, 26.1, 27.3, and 31.6, ± 0.2 degrees 2 theta. Form K3 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 23.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 4.0, 5.8, 6.8, 9.4, 14.7, 27.4, and 31.7, ± 0.2 degrees 2 theta. Form K4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 24.
In another aspect, the present invention provides an amorphous form of an esomeprazole lithium salt, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 25.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately

6.3, ± 0.2 degrees 2 theta. Form L1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 26.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.6, 6.3, 17.2, 22.7, 23.1, and 37.1, ± 0.2 degrees 2 theta. Form L2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 27.
In yet another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 4.9, 6.4, and 22.9, ± 0.2 degrees 2 theta. Form L3 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 28.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.4, 6.3, 18.3, 19.0, 22.5, 24.1, 27.8, and 22.8, ±0.2 degrees 2 theta. Form L4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 29.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L5, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 6.3, 22.6, and 22.9, ± 0.2 degrees 2 theta. Form L5 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 30.
In a further aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L6, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 6.2, 11.1, 17.1, 18.1, 18.9, 20.3, 22.5, 23.0, 27.9, 32.2, and 26.9, ± 0.2 degrees 2 theta. Form L6 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 31.

In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L7, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.4, 6.2, 10.9, 12.2, 16.9, 17.2, 18.2, 19.2, 22.3, 22.7, and 28.8, ± 0.2 degrees 2 theta. Form L7 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 32.
In the above process, dissolving esomeprazole free base in n-butanol at about 25-30°C followed by addition of cupper sulfate dissolved in methanol at about 25-30°C affords crystalline Form C1 of esomeprazole copper.
In the above process, dissolving esomeprazole free base in N,N-dimethyl formamide (DMF) at about 25-30°C followed by addition of cupper sulfate dissolved in methanol at about 25-30°C affords crystalline Form C2 of esomeprazole copper.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of cupper sulfate dissolved in methanol at about 25-30°C affords amorphous esomeprazole copper.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of zinc sulfate dissolved in water at about 25-30°C affords amorphous esomeprazole zinc.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of zinc chloride dissolved in water at about 25-30°C affords crystalline Form Z1 of esomeprazole zinc.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of zinc chloride dissolved in water at about 25-30°C affords amorphous esomeprazole zinc.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords amorphous esomeprazole barium.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B1 of esomeprazole barium.

In the above process, dissolving esomeprazole freebase in acetone at about 25-30°C followed by addition of barium hydroxide dissolved in acetone at about 25-30°C affords crystalline Form B2 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in toluene at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B3 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in dichloromethane at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B4 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in tetrahydrofuran at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B5 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in acetonitrile at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B6 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P1 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in ethyl acetate at about 25-30°C followed by addition of potassium hydroxide dissolved in water at about 25-30°C affords crystalline Form P2 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in toluene at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P3 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in acetonitrile at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P4 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in dichlorormethane at about 25-30°C followed by addition of potassium hydroxide

dissolved in methanol at about 25-30°C affords crystalline Form P5 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in acetone at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P6 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in isopropyl alcohol at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P7 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of calcium chloride dissolved in water at about 25-30°C affords crystalline Form K1 of esomeprazole calcium.
In the above process, dissolving esomeprazole free base in n-butanol and methanol at about 25-30°C followed by addition of calcium chloride dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with ethyl acetate affords crystalline Form K2 of esomeprazole calcium.
In the above process, dissolving esomeprazole free base in toluene and methanol at about 25-30°C followed by addition of calcium chloride dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with toluene affords crystalline Form K3 of esomeprazole calcium.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of calcium chloride dissolved in methanol at about 25-30°C, thes distilling under vacuum and mixing a residue with acetone affords crystalline Form K4 of esomeprazole calcium.
In the above process, dissolving esomeprazole free base in methanol at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C affords amorphous esomeprazole lithium.
In the above process, dissolving esomeprazole free base in acetone at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with acetone affords crystalline Form L1 of esomeprazole lithium.

In the above process, dissolving esomeprazole free base in toluene at about 25-30°C followed by addition of lithium hydroxide dissolved in toluene at about 25-30°C, then distilling under vacuum and mixing a residue with toluene affords crystalline Form L2 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in isopropyl alcohol at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with isopropyl alcohol affords crystalline Form L3 esomeprazole lithium.
In the above process, dissolving esomeprazole free base in acetonitrile at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with acetonitrile affords crystalline Form L4 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in tetrahydrofuran at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with tetrahydrofuran affords crystalline Form L5 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in dichloromethane at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with dichloromethane affords crystalline Form L6 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in ethyl acetate at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with ethyl acetate affords crystalline Form L7 of esomeprazole lithium.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is an X-ray powder diffraction ("XRPD") pattern of ezomeprazole copper crystalline Form C1.
Fig. 2 is an XRPD pattern of crystalline ezomeprazole copper Form C1.
Fig. 3 is an XRPD pattern of an amorphous form of esomeprazole copper.

Fig. 4 is an XRPD pattern of an amorphous form of esomeprazole zinc.
Fig. 5 is an XRPD pattern of ezomeprazole copper crystalline Form Z1.
Fig. 6 is an XRPD pattern of an amorphous form of esomeprazole zinc.
Fig. 7 is an XRPD pattern of an amorphous form of esomeprazole barium.
Fig. 8 is an XRPD pattern of ezomeprazole barium crystalline Form B1.
Fig. 9 is an XRPD pattern of ezomeprazole barium crystalline Form B2.
Fig. 10 is an XRPD pattern of ezomeprazole barium crystalline Form B3.
Fig. 11 is an XRPD pattern of ezomeprazole barium crystalline Form B4.
Fig. 12 is an XRPD pattern of ezomeprazole barium crystalline Form B5.
Fig. 13 is an XRPD pattern of ezomeprazole barium crystalline Form B6.
Fig. 14 is an XRPD pattern of ezomeprazole potassium crystalline Form P1.
Fig. 15 is an XRPD pattern of ezomeprazole potassium crystalline Form P2.
Fig. 16 is an XRPD pattern of ezomeprazole potassium crystalline Form P3.
Fig. 17 is an XRPD pattern of ezomeprazole potassium crystalline Form P4.
Fig. 18 is an XRPD pattern of ezomeprazole potassium crystalline Form P5.
Fig. 19 is an XRPD pattern of ezomeprazole potassium crystalline Form P6.
Fig. 20 is an XRPD pattern of ezomeprazole potassium crystalline Form
P7.
Fig. 21 is an XRPD pattern of ezomeprazole calcium crystalline Form K1.
Fig. 22 is an XRPD pattern of ezomeprazole calcium crystalline Form K2.
Fig. 23 is an XRPD pattern of ezomeprazole calcium crystalline Form K3.
Fig. 24 is an XRPD pattern of ezomeprazole calcium crystalline Form K4.
Fig. 25 is an XRPD pattern of an amorphous form of esomeprazole lithium.
Fig. 26 is an XRPD pattern of ezomeprazole lithium crystalline Form L1.

Fig. 27 is an XRPD pattern of ezomeprazole lithium crystalline Form L2. Fig. 28 is an XRPD pattern of ezomeprazole lithium crystalline Form L3. Fig. 29 is an XRPD pattern of ezomeprazole lithium crystalline Form L4. Fig. 30 is an XRPD pattern of ezomeprazole lithium crystalline Form L5. Fig. 31 is an XRPD pattern of ezomeprazole lithium crystalline Form L6. Fig. 32 is an XRPD pattern of ezomeprazole lithium crystalline Form L7.
DETAILED DESCRIPTION OF THE INVENTION In one aspect, the present invention provides a process for the preparation of esomeprazole salts, which process comprises:
1) providing a solution comprising esomeprazole in a suitable organic solvent under suitable conditions;
2) adding a suitable base to the solution of step 1) under suitable conditions;
3) recovering a solid from step 2) under suitable conditions to afford the desired salt of esomeprazole.
Step 1) involves providing a solution comprising esomeprazole in a suitable organic solvent under suitable conditions.
The solution of esomeprazole may be obtained by dissolving esomeprazole free base in a suitable solvent, or such a solution may be obtained directly from a reaction in which esomeprazole free base is formed.
Suitable organic solvents that can be used to dissolve the free base include but are not limited to: C1-C4 alcohols such as methanol, ethanol, propanol, n-butanol, isopropyl alcohol and the like; C2-C6 ketone solvents such as acetone, ethyl methyl ketone, and diethyl ketone; chlorinated solvents, such as C1-C6 straight chain or branched chlorohydrocarbons including dichloromethane, ethylene dichloride, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; ethers such as tetrahydrofuran ("THF"), diethyl ether, methyl tertiary-butyl ether, 1,4-dioxane and the like; hydrocarbon solvents such as toluene, xylene, cyclohexane and the like; esters such as ethyl acetate, isopropyl acetate, tertiary-butyl acetate and the like; nitriles such as acetonitrile, propionitrile and the like ; aprotic polar solvents such as

dimethyl sulfoxide ("DMSO"), N,N-dimethylformamide ("DMF"), dimethyl acetamide ("DMAC"), N-methylpyrrolidone ("NMP") and the like; and mixtures thereof or their combinations with water in various proportions.
Any solvent is acceptable as long as it provides a clear solution of the esomeprazole, at the temperature of operation.
The dissolution temperatures can range from about 20 to about 100° C depending on the solvent used for dissolution. Any other temperature is also acceptable as long as the stability of ezomeprazole free base is not compromised and a clear solution is obtained.
The maintenance time for dissolution to occur for getting a homogenous solution can be any desired time periods to achieve the desired product yield and purity, times from about 1 to 10 hours, or longer, frequently being adequate.
Step 2) involves adding a suitable base to the solution of step 1) under suitable conditions.
Suitable alkali metal and alkaline earth metal salts and hydroxides that can be used as bases include but are not limited to lithium hydroxide, copper sulfate, barium hydroxide, zinc chloride, potassium hydroxide, lithium hydroxide, calcium hydroxide, and the like.
The solution of the metal salts and hydroxides can be prepared by dissolving the metal salts in a suitable solvents such as but not limited to: water; and C1-C4 alcohols such as methanol, ethanol, propanol, n-butanol, isopropyl alcohol and the like;
Suitable temperatures for addition of metal salt solution range from about 10°C to about 50°C, or from about 20°C to about 30°C.
The mixtures of esomeprazole and the base can be maintained for any desired time periods to achieve the desired product yield and purity, times from about 1 to 10 hours, or longer, frequently being adequate.
Stirring or other alternate methods such as shaking, agitation and the like, that mix the contents is done for crystallization to occur, the reaction mass may be maintained further at temperatures lower than the concentration temperatures such as for example below about 10 °C to about 25 °C, for a period of time as

required for a more complete formation of the product. The exact cooling temperature and time required for complete crystallization can be readily determined by a person skilled in the art and will also depend on parameters such as concentration and temperature of the solution or slurry.
Optionally crystallization may be initiated by methods such as cooling, seeding, partial removal of the solvent from the solution, by adding an anti-solvent to the solution or a combination thereof.
Step 3) involves recovering a solid from step 2) under suitable conditions to afford the desired salt of esomeprazole.
The method by which the solid material is recovered from the final mixture, with or without cooling below the operating temperature, can be any of techniques such as filtration by gravity or by suction, centrifugation, or slow evaporation and the like. The crystals so isolated will carry a small proportion of occluded mother liquor containing a higher percentage of impurities. If desired the crystals can be washed with a solvent to wash out the mother liquor.
The wet cake obtained in step 3) may optionally be further dried. Drying can be suitably carried out in a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like. The drying can be carried out at temperatures of about 35°C to about 90°C with or without vacuum. The drying can be carried out for any desired time until the required product purity is achieved, time periods from about 1 to 20 hours, or longer, frequently being sufficient.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole copper salt designated herein as Form C1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 22.6, 23.5, 25.5, 31.8, 33.9, and 37.8, ± 0.2 degrees 2 theta. Form C1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 1.
In yet another aspect, the present invention provides a crystalline polymorph of an esomeprazole copper salt designated herein as Form C2, characterized by X-ray powder diffraction pattern with characteristic peaks at

approximately 18.6, 19.0, 22.6, and 37.8, ± 0.2 degrees 2 theta. Form C2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 2.
In another aspect, the present invention provides an amorphous form of an esomeprazole copper salt, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 3.
In a further aspect, the present invention provides an amorphous form of an esomeprazole zinc salt, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 4.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole zinc salt designated herein as Form Z1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 27.2 and 31.6, ± 0.2 degrees 2 theta. Form Z1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 5.
In a still further aspect, the present invention provides an amorphous form of an esomeprazole zinc salt characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 6.
In another aspect, the present invention provides an amorphous form of an esomeprazole barium salt characterized by an X-ray powder diffraction pattern, substantially in accordance with Fig. 7.
In an aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 16.0,16.2, and 24.3, ± 0.2 degrees 2 theta. Form B1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 8.
In an aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 26.0, 16.2, 21.1, 27.3, 27.3, 39.2 and 40.5, ± 0.2 degrees 2 theta. Form B2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 9.

In another aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately
5.4, 6.4, 15.9, 16.2, 17.8, 24.3, 24.3, 26.0, and 28.1, ± 0.2 degrees 2 theta. Form
B3 is also characterized by an X-ray powder diffraction pattern substantially in
accordance with Fig. 10.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.7, 13.4, 16.0, 16.3, 21.2, 24.4, 23.8, and 27.3, ± 0.2 degrees 2 theta. Form B4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 11.
In an aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B5, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 13.3, 15.9, 16.2, 24.7, 26.0, and 27.2, ± 0.2 degrees 2 theta. Form B5 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 12.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole barium salt designated herein as Form B6, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately
5.5, 6.9, 13.4, 15.9, 16.2, 21.2, 24.8, and 27.2, ± 0.2 degrees 2 theta. Form B6 is
also characterized by an X-ray powder diffraction pattern substantially in
accordance with Fig. 13.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 6.3, 16.2, 18.5, 23.7,24.6,25.1, and 27.8, ± 0.2 degrees 2 theta. Form P1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 14.

In a further aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.0, 17.5, 18.8, 22.5, 22.8, 28.7, 29.2, 33.6, 35.4, 35.6, and 36.2, ± 0.2 degrees 2 theta. Form P2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 15.
In a still further aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.5, 14.3, 18.3, 18.9, 19.9, 21.3, 22.4, 22.9, 25.8, and 31.1, ±0.2 degrees 2 theta. Form P3 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 16.
In a yet further aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.5, 14.3, 18.3, 18.9, 19.9, 21.3, 22.4, 22.9, 25.8, and 31.13, ±0.2 degrees 2 theta. Form P4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 17.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P5, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.5, 14.9, 18.9, 19.9, and 22.9, ± 0.2 degrees 2 theta. Form P5 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 18.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P6, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 7.4, 18.2, 21.3, 23.0, and 31.02, ± 0.2 degrees 2 theta. Form P6 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 19.

In another aspect, the present invention provides a crystalline polymorph of an esomeprazole potassium salt designated herein as Form P7, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.2, 7.2, 18.1,18.9, and 22.8, ± 0.2 degrees 2 theta. Form P7 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 20.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.4,11.4, 13.0, and 24.2, ± 0.2 degrees 2 theta. Form K1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 21.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 6.4, 6.7, 26.1, and 31.6, ± 0.2 degrees 2 theta. Form K2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 22.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.9,6.2,8.8, 9.3, 14.6, 26.1, 27.3, and 31.6, ± 0.2 degrees 2 theta. Form K3 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 23.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole calcium salt designated herein as Form K4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 4.0, 5.8,6.8, 9.4, 14.7,27.4, and 31.7, ± 0.2 degrees 2 theta. Form K4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 24.
In another aspect, the present invention provides an amorphous form of an esomeprazole lithium salt, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 25.

In another aspect, the present invention provides a crysiauine poiymorpn of an esomeprazole lithium salt designated herein as Form L1, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 6.3, ± 0.2 degrees 2 theta. Form L1 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 26.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L2, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.6, 6.3,17.2, 22.7,23.1, and 37.1, ± 0.2 degrees 2 theta. Form L2 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 27.
In yet another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L3, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 4.9, 6.4, and 22.9, ± 0.2 degrees 2 theta. Form L3 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 28.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L4, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.4, 6.3, 18.3, 19.0,22.5, 24.1, 27.8, and 22.8, ± 0.2 degrees 2 theta. Form L4 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 29.
In another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L5, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.5, 6.3, 22.6, and 22.9, ± 0.2 degrees 2 theta. Form L5 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 30.
In a further aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L6, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately

5.5, 6.2, 11.1, 17.1, 18.1, 18.9, 20.3, 22.5, 23.0, 27.9, 32.2, and 26.9, ± 0.2 degrees 2 theta. Form L6 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 31.
In still another aspect, the present invention provides a crystalline polymorph of an esomeprazole lithium salt designated herein as Form L7, characterized by an X-ray powder diffraction pattern with characteristic peaks at approximately 5.4, 6.2, 10.9, 12.2, 16.9, 17.2, 18.2, 19.2, 22.3, 22.7, and 28.8, ± 0.2 degrees 2 theta. Form L7 is also characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 32.
In the above process, dissolving esomeprazole freebase in n-butanol at about 25-30°C followed by addition of cupper sulfate dissolved in methanol at about 25-30°C affords crystalline Form C1 of esomeprazole copper.
In the above process, dissolving esomeprazole free base in N,N-dimethyl formamide (DMF) at about 25-30°C followed by addition of cupper sulfate dissolved in methanol at about 25-30°C affords crystalline Form C2 of esomeprazole copper.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of cupper sulfate dissolved in methanol at about 25-30°C affords amorphous esomeprazole copper.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of zinc sulfate dissolved in water at about 25-30°C affords amorphous esomeprazole zinc.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of zinc chloride dissolved in water at about 25-30°C affords crystalline Form Z1 of esomeprazole zinc.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of zinc chloride dissolved in water at about 25-30°C affords amorphous esomeprazole zinc.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords amorphous esomeprazole barium.

In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B1 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in acetone at about 25-30°C followed by addition of barium hydroxide dissolved in acetone at about 25-30°C affords crystalline Form B2 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in toluene at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B3 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in dichlorormethane at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B4 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in tetrahydrofuran at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B5 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in acetonitrile at about 25-30°C followed by addition of barium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form B6 of esomeprazole barium.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P1 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in ethyl acetate at about 25-30°C followed by addition of potassium hydroxide dissolved in water at about 25-30°C affords crystalline Form P2 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in toluene at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P3 of esomeprazole potassium.

In the above process, dissolving esomeprazole freebase in acetonitrile at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P4 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in dichlorormethane at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P5 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in acetone at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P6 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in isopropyl alcohol at about 25-30°C followed by addition of potassium hydroxide dissolved in methanol at about 25-30°C affords crystalline Form P7 of esomeprazole potassium.
In the above process, dissolving esomeprazole freebase in water at about 25-30°C followed by addition of calcium chloride dissolved in water at about 25-30°C affords crystalline Form K1 of esomeprazole calcium.
In the above process, dissolving esomeprazole freebase in n-butanol and methanol at about 25-30°C followed by addition of calcium chloride dissolved in methanol at about 25-30°C, then distilling under vaccum and mixing a residue with ethyl acetate affords crystalline Form K2 of esomeprazole calcium.
In the above process, dissolving esomeprazole free base in toluene and methanol at about 25-30°C followed by addition of calcium chloride dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with toluene affords crystalline Form K3 of esomeprazole calcium.
In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of calcium chloride dissolved in methanol at about 25-30°C, thes distilling under vacuum and mixing a residue with acetone affords crystalline Form K4 of esomeprazole calcium.

In the above process, dissolving esomeprazole freebase in methanol at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C affords amorphous esomeprazole lithium.
In the above process, dissolving esomeprazole free base in acetone at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with acetone affords crystalline Form L1 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in toluene at about 25-30°C followed by addition of lithium hydroxide dissolved in toluene at about 25-30°C, then distilling under vacuum and mixing a residue with toluene affords crystalline Form L2 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in isopropyl alcohol at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with isopropyl alcohol affords crystalline Form L3 esomeprazole lithium.
In the above process, dissolving esomeprazole free base in acetonitrile at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with acetonitrile affords crystalline Form L4 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in tetrahydrofuran at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with tetrahydrofuran affords crystalline Form L5 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in dichloromethane at about 25»30°C followed by addition of lithium hydroxide dissolved in methanol at about 25-30°C, then distilling under vacuum and mixing a residue with dichloromethane affords crystalline Form L6 of esomeprazole lithium.
In the above process, dissolving esomeprazole free base in ethyl acetate at about 25-30°C followed by addition of lithium hydroxide dissolved in methanol

at about 25-30°C, then distilling under vacuum and mixing a residue with ethyl acetate affords crystalline Form L7 of esomeprazole lithium.
X-ray powder diffraction patterns reported herein were determined using a Bruker AXS D8 Advance powder X-ray diffractometer with a Cu K alpha radiation source. X-ray powder diffraction patterns were obtained using a Bruker X-Ray powder diffractometer, goniometer model 1050/70 at a scanning speed of 1 degree per minute, with a Cu radiation of A=1.5418 A.
The starting material for the present processes can be esomeprazole obtained by any method. The starting material for a process can also be in any polymorphic form, such as amorphous or crystalline forms of esomeprazole or a mixture of amorphous and crystalline forms of esomeprazole obtained by any method.
Optionally, seeding crystals of polymorphic crystalline forms of esomeprazole salts can also be used in a process, to aid in crystal formation.
In yet another embodiment of the present invention, there is provided pharmaceutical compositions containing a therapeutically effective amount of polymorphs of esomeprazole salts of the present invention, together with one or more pharmaceutically acceptable excipients.
The pharmaceutical composition comprising esomeprazole salts of the invention along with one or more pharmaceutically acceptable excipients may be formulated as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets, and capsules; liquid oral dosage forms such as but not limited to syrups, suspensions, dispersions, and emulsions; and injectable preparations such as but not limited to solutions, dispersions, and freeze dried compositions. Formulations may be in the form of immediate release, delayed release or modified release. Further, immediate release compositions may be conventional, dispersible, chewable, mouth dissolving, or flash melt preparations, and modified release compositions that may comprise hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic, release rate controlling substances to form matrix or reservoir systems or combinations of matrix and reservoir systems. The compositions may be prepared by direct

blending, dry granulation, wet granulation or by extrusion and spheronization. Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated or modified release coated. Compositions of the present invention may further comprise one or more pharmaceutical^ acceptable excipients.
Pharmaceutically acceptable excipients that find use in the present invention include, but are not limited to: diluents such as starch, pregelatinized starch, lactose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar and the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, pregelatinized starch and the like; disintegrants such as starch, sodium starch glycolate, pregelatinized starch, crospovidone, croscarmellose sodium, colloidal silicon dioxide and the like; lubricants such as stearic acid, magnesium stearate, zinc stearate and the like; glidants such as colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic or cationic or neutral surfactants; complex forming agents such as various grades of cyclodextrins, resins; release rate controlling agents such as hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, methylcellulose, various grades of methyl methacrylates, waxes and the like. Other pharmaceutically acceptable excipients that are of use include but are not limited to film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants and the like.
The processes of present invention are simple, cost-effective, eco-friendly, reproducible, scalable, and robust to produce esomeprazole salts with high purity.
Certain specific aspects and embodiments of the present invention will be explained in greater detail with reference to the following examples, which are provided by way of illustration only and should not be construed as limiting the scope of the invention in any manner.
EXAMPLES

EXAMPLE 1: PREPARATION OF ESOMEPRAZOLE COPPER CRYSTALLINE FORM C1
20 g of esomeprazole free base of Formula I and 200 ml of n-butanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 12.2 g of copper sulfate dissolved in 100 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 60 minutes. The formed solid was filtered and the solid was washed with 100 ml of n-butanol. Solid obtained was dried at about 50°C under vacuum for about 2-3 hours to afford 16 g of the title compound.
The crystalline Form C1 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 1.
EXAMPLE 2: PREPARATION OF ESOMEPRAZOLE COPPER CRYSTALLINE FORM C2
20 g of esomeprazole free base of Formula I and 200 ml of N,N-dimethyl formamide (DMF) were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 12.2 g of copper sulfate dissolved in 100 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 60 minutes. The formed solid was filtered and the solid was washed with 100 ml of methanol. Solid obtained was dried at about 50°C under vacuum for about 2-3 hours to afford 17 g of the title compound.
The crystalline Form C2 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 2.
EXAMPLE 3: PREPARATION OF ESOMEPRAZOLE COPPER AMORPHOUS FORM
20 g of esomeprazole free base of Formula I and 100 ml of dichloromethane were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 6.1 g of copper sulfate dissolved in 50 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The solvents were distilled completely at about 40

°C under vaccum to afford 5.8 g of the title compound, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 3.
EXAMPLE 4: PREPARATION OF ESOMEPRAZOLE ZINC SALT AMORPHOUS FORM
10 g of esomeprazole free base of Formula I and 100 ml of water were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 5.2 g of zinc sulfate dissolved in 100 ml of water was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The formed solid was filtered and the solid was washed with 50 ml of water. Solid obtained was dried at about 50°C under vacuum for about 2-3 hours to afford 16 g of the title compound, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 4.
EXAMPLE 5: PREPARATION OF ESOMEPRAZOLE ZINC CRYSTALLINE FORM Z1
20 g of esomeprazole free base of Formula I and 200 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 5.2 g of zinc chloride dissolved in 100 ml of water was added slowly at about 25-30°C over about 10-20 minutes and stirred for 2-3 hours. The formed solid was filtered and washed with 50 ml of water. The solid was dried under vacuum at 50°C to afford 16 g of the title compound.
The crystalline Form Z1 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 5.
EXAMPLE 6: PREPARATION OF ESOMEPRAZOLE ZINC AMORPHOUS FORM
20 g of esomeprazole free base of Formula I and 200 ml of water were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 5.2 g of zinc chloride dissolved in 100 ml of water was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours.

The formed solid was filtered and the solid was washed with 100 ml of water. The solid obtained was dried at about 25-30°C for about 3-4 hours to afford 37 g of the title compound, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 6.
EXAMPLE 7: PREPARATION OF ESOMEPRAZOLE BARIUM AMORPHOUS FORM
10 g of esomeprazole free base of Formula I and 100 ml of ethyl acetate were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 9.1 g of barium hydroxide dissolved in 20 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The formed solid was filtered and the solid was washed with 40 ml of ethyl acetate. The solid obtained was dried at about 50-60°C under vacuum to afford 9 g of the title compound, characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 7.
EXAMPLE 8: PREPARATION OF ESOMEPRAZOLE BARIUM CRYSTALLINE FORM B1
9.1 g of barium hydroxide and 100 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 10 g of esomeprazole free base of Formula I dissolved in 100 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The obtained solution was poured into a glass tray and allowed to evaporate to dryness overnight to afford 14 g of the title compound.
The crystalline Form B1 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 8.
EXAMPLE 9: PREPARATION OF ESOMEPRAZOLE BARIUM CRYSTALLINE FORM B2
9.1 g of barium hydroxide and 40 ml of acetone was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 10 g

of esomeprazole free base of Formula I dissolved in 100 ml acetone was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The obtained solution was poured into a glass tray and allowed to evaporate to dryness overnight to afford 13 g of the title compound.
The crystalline Form B2 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 9.
EXAMPLE 10: PREPARATION OF ESOMEPRAZOLE BARIUM CRYSTALLINE FORM B3
9.1 g of barium hydroxide and 20 ml of methanol was charged into a clean and dry 4 neck round bottom flask and stirred for about 10 minutes. 10 g of esomeprazole free base of Formula I dissolved in 100 ml of toluene was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The obtained solution was poured into a glass tray and allowed to evaporate to dryness overnight to afford 13.3 g of the title compound.
The crystalline Form B3 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 10.
EXAMPLE 11: PREPARATION OF ESOMEPRAZOLE BARIUM CRYSTALLINE FORM B4
9.1 g of barium hydroxide and 20 ml of methanol was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 10 g of esomeprazole free base of Formula I dissolved in 100 ml of dichloromethane was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The obtained solution was poured in to a glass tray and allowed to evaporate to dryness overnight to afford 13.4 g of the title compound
The crystalline Form B4 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 11.

EXAMPLE 12: PREPARATION OF ESOMEPRAZOLE BARIUM CRYSTALLINE FORM B5
9.1 g of barium hydroxide and 20 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 10 g of esomeprazole free base of Formula I dissolved in 100 ml of tetrahydrofuran (THF) was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The obtained solution was poured into a glass tray and allowed to evaporate to dryness overnight to afford 14 g of the title compound.
The crystalline Form B5 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 12.
EXAMPLE 13: PREPARATION OF ESOMEPRAZOLE BARIUM CRYSTALLINE FORM B6
9.1 g of barium hydroxide and 20 ml of methanol were charged into a clean and dry 4 neck round bottom flask, followed by stirring for about 10 minutes. 10 g of esomeprazole free base of Formula I dissolved in 100 ml of acetonitrile was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 2-3 hours. The solution obtained was poured into a glass tray and allowed to evaporate to dryness overnight to afford 12.2 g of the title compound.
The crystalline Form B6 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 13.
EXAMPLE14: PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P1
16.2 g of potassium hydroxide and 300 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10-15 minutes. 100 g of esomeprazole free base of Formula I dissolved in 150 ml of methanol was added slowly over about 10-20 minutes. 100 ml of toluene was added slowly over about 10 minutes and stirred for about 12 hours. Formed solid

was filtered and the solid was washed with 100 ml of toluene. Solid obtained was dried at about 40-50°C under vacuum to afford 80 g of the title compound. The crystalline Form P1 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 14.
EXAMPLE 15 : PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P2
13.3 g of esomeprazole free base of Formula I and 85.2 ml of ethyl acetate was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.72 g of potassium hydroxide dissolved in 4 ml of water was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 2-3 hours followed by addition of 2 ml of methanol. The resulting solution was stirred at about 20-30°C for about 2-3 hours. The solution was distilled completely at about 50°C under vacuum to afford a foamy yellow solid that was scraped from the flask to afford 11.2 g of the title compound.
The crystalline Form P2 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 15.
EXAMPLE 16: PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P3
10 g of esomeprazole free base of Formula I and 70 ml of toluene were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.623 g of potassium hydroxide dissolved in 35 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resulting solution was distilled completely at about 60 °C under vacuum and 2x60 ml of toluene was charged and distilled to dryness. To the obtained residue, 35 ml toluene was charged and stirred for about 20-30 minutes. The solid was filtered and was washed with 35 ml of toluene. The solid obtained was dried at about 65°C under vacuum to afford the title compound.
The crystalline Form P3 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 16.

EXAMPLE 17: PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P4
10 g of esomeprazole free base of Formula I and 70 ml of acetonitrile was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes, 1.623 g of potassium hydroxide dissolved in 35 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The formed solid was filtered and was washed with 35 ml of acetonitrile. The solid obtained was dried at about 60-70°C under vacuum for about 3 hours to afford 3.9 g of the title compound.
The crystalline Form P4 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 17.
EXAMPLE18: PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P5
10 g of esomeprazole free base of Formula I and 70 ml of dichloromethane were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.623 g of potassium hydroxide dissolved in 35 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The solution obtained was distilled completely at about 55°C under vacuum, and 60 ml of dichloromethane was charged and distilled to dryness. To the residue, 60 ml of dichloromethane was added and stirred at about 25-30°C for about 45-60 minutes. The solid was filtered and was washed with 35 ml of dichloromethane. The solid obtained was dried at about 65°C under vacuum to afford 3.4 g of the title compound.
The crystalline Form P5 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 18.

EXAMPLE19: PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P6
10 g of esomeprazole free base of Formula I and 70 ml of acetone was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. A mixture of methanolic potassium hydroxide solution (1.623 g KOH dissolved in 35 ml of methanol) was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. Formed solid was filtered and the solid was washed with 35 ml of acetone. The solid obtained was dried at about 60°C under vacuum for about 3 hours to afford 5.3 g of the title compound.
The crystalline Form P6 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 19. .
EXAMPLE 20: PREPARATION OF ESOMEPRAZOLE POTASSIUM CRYSTALLINE FORM P7
10 g of esomeprazole free base of Formula I and 70 ml of isopropyl alcohol was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. A mixture of methanolic potassium hydroxide solution (1.623 g KOH dissolved in 35 ml of methanol) was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The separated solid was filtered and the solid was washed with 35 ml of isopropyl alcohol. The solid obtained was dried at about 60-70°C under vacuum for about 3 hours to afford 5.3 g of the title compound.
The crystalline Form P7 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 20.
EXAMPLE 21: PREPARATION OF ESOMEPRAZOLE CALCIUM CRYSTALLINE FORM K1
14.8 g of esomeprazole free base of Formula I and 70 ml of water were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.6 g of calcium chloride dissolved in 40 ml water was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours.

The formed solid was filtered and was washed with 35 ml of water. The solid obtained was dried at about 60°C under vacuum to afford 7.7 g of the title compound.
The crystalline Form K1 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 21.
EXAMPLE 22: PREPARATION OF ESOMEPRAZOLE CALCIUM CRYSTALLINE FORM K2
10 g of esomeprazole free base of Formula I, 35 ml of n-butanol and 70 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.6 g of calcium chloride dissolved in 40 ml methanol was added slowly at about 25-30°C over about 10-20 minutes and was stirred for about 3 hours. The unwanted solid was filtered and washed with 15 ml of n-butanol. The clear filtrate obtained was distilled completely at about 50 °C under vacuum to obtain a semi-solid residue. To the residue, 80 ml of ethyl acetate was added and distilled completely at about 60°C under vacuum to afford a residue. To the resultant residue 35 ml of ethyl acetate was charged and stirred at about 20-30°C for about 30 minutes. The solid was filtered and washed with 35 ml of ethyl acetate. The solid obtained was dried at about 50 °C under vacuum for about 3-4 hours to afford 20 g of the title compound.
The crystalline Form K2 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 22.
EXAMPLE 23: PREPARATION OF ESOMEPRAZOLE CALCIUM CRYSTALLINE FORM K3
10 g of esomeprazole free base of Formula I, 35 ml toluene and 70 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.6 g of calcium chloride dissolved in 40 ml methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The unwanted solid was filtered and the solid was washed with 15 ml of toluene. The clear filtrate obtained was distilled completely

at about 50 °C under vacuum to afford a solid residue. To the residue, 35 ml of toluene was charged and distilled completely at about 60 °C under vacuum to obtain a residue. To the residue, 60 ml of toluene was charged and stirred at about 20-30°C for about 30 minutes. The solid was filtered and was washed with 35 ml of toluene. The solid obtained was dried at 50°C under vacuum for about 2-3 to afford 11.8 g of the title compound.
The crystalline Form K3 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 23.
EXAMPLE 24: PREPARATION OF ESOMEPRAZOLE CALCIUM CRYSTALLINE FORM K4
10 g of esomeprazole free base of Formula I and 70 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.6 g of calcium chloride dissolved in 40 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The unwanted solid was filtered and the solid was washed with 35 ml of methanol. The filtrate obtained was distilled completely at about 60°C under vacuum to afford a residue. To the residue, 50 ml of methanol was charged and distilled completely at 50-60°C under vacuum to obtain a residue. To the residue, 70 ml of acetone was charged and stirred at about 30°C for about 30 minutes. The solid was filtered and was washed with 35 ml of acetone. The solid obtained was dried at about 60°C under vacuum for about 3-4 hours to afford 15.6 g of the title compound.
The crystalline Form K4 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 24.
EXAMPLE 25: PREPARATION OF ESOMEPRAZOLE LITHIUM AMORPHOUS FORM
10 g of esomeprazole free base of Formula I and 100 ml of methanol were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 40 ml methanol was

added slowly at about 25-30°C over about 10-20 minutes and stirred for about 30 minutes. The resultant clear solution was distilled completely at about 50 °C under vacuum to obtain 13.5 g of the title compound.
The amorphous form obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 25.
EXAMPLE 26: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L1
10 g of esomeprazole free base of Formula I and 100 ml acetone of were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 30 ml methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resultant clear solution was distilled until about 80-90% of the original volume was removed at about 50°C under vacuum, 100 ml of acetone was charged, and the mixture was stirred about 25-30°C for about 30-60 minutes. The solid that formed was filtered and was washed with 20 ml of acetone. The solid obtained was dried at about 70°C under vacuum for about 3-4 hours to afford 4 g of the title compound.
The crystalline Form L1 obtained by above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 26.
EXAMPLE 27: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L2
10 g of esomeprazole free base of Formula I and 100 ml of toluene were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 30 ml of toluene was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resultant clear solution was distilled until about 80-90% of its original volume was removed at about 50°C under vacuum, 100 ml of toluene was added and the mixture was stirred at about 25-30°C for about 30-60 minutes. The formed solid was filtered and the solid was washed with 20 ml of toluene. The

solid obtained was dried at about 70°C under vacuum for about 3-4 hours to afford 5 g of the title compound.
The crystalline Form L2 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 27.
EXAMPLE 28: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L3
10 g of esomeprazole free base of Formula I and 100 ml of isopropyl alcohol was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 30 ml methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resultant clear solution was distilled until about 80-90% of its original volume was removed at about 50°C under vacuum, 100 ml of isopropyl alcohol was charged and the mixture was stirred at about 25-30°C for about 30-60 minutes. The formed solid was filtered and was washed with 20 ml of isopropyl alcohol. The solid obtained was dried at about 70°C under vacuum to afford 2.1 g of the title compound.
The crystalline Form L3 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 28.
EXAMPLE 29: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L4
10 g of esomeprazole free base of Formula I and 100 ml of acetonitrile were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 30 ml methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resultant clear solution was distilled to remove about 80-90% of the original volume at about 50°C under vacuum, 100 ml of acetonitrile was added and the mixture was stirred at about 25-30°C for about 30-60 minutes. The formed solid was filtered and was washed with 20 ml of acetonitrile. The solid

obtained was dried at about 70°C under vacuum for about 2-3 hours to afford 6.2 g of the title compound.
The crystalline Form L4 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 29.
EXAMPLE 30: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L5
10 g of esomeprazole free base of Formula I and 100 ml of tetrahydrofuran were charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 30 ml of methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resultant clear solution was distilled to remove about 80-90% of the original volume at about 50°C under vacuum, 100 ml of tetrahydrofuran (THF) was added and the mixture was stirred at about 25-30°C for about 30-60 minutes. The formed solid was filtered and washed with 20 ml of tetrahydrafuran. The solid obtained was dried at about 70°C under vacuum for about 2-3 hours to afford 6 g of the title compound.
The crystalline Form L5 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 30.
EXAMPLE 31: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L6
10 g of esomeprazole free base of Formula I and 100 ml of dichloromethane was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 30 ml methanol was added slowly at about 25-30°C over about 10-20 minutes and stirred for about 3 hours. The resultant clear solution was distilled to remove about 80-90% of the original volume at about 50°C under vacuum, 100 ml of dichloromethane was charged and the mixture was stirred at about 25-30°C for about 30-60 minutes. The formed solid was filtered and was washed with 20 ml

of dichloromethane. The solid obtained was dried at about 70°C under vacuum for about 2-3 hours to afford 7.5 g of the title compound.
The crystalline Form L6 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 31.
EXAMPLE 32: PREPARATION OF ESOMEPRAZOLE LITHIUM CRYSTALLINE FORM L7
10 g of esomeprazole free base of Formula I and 100 ml of ethyl acetate was charged into a clean and dry 4 neck round bottom flask followed by stirring for about 10 minutes. 1.2 g of lithium hydroxide dissolved in 50 ml methanol was added slowly at about 25-30°C over about 10-20 mins and stirred for about 3 hours. The resultant clear solution was distilled to remove about 80-90% of the original volume at about 50°C under vacuum, 100 ml of ethyl acetate was added and the mixture was stirred at about 25-30°C for about 30-60 minutes. The solid that formed was filtered and was washed with 20 ml of ethyl acetate. The solid obtained was dried at about 70°C under vacuum for about 2-3 hours to afford 12.8 g of the title compound.
The crystalline Form L7 obtained by the above process is characterized by an X-ray powder diffraction pattern substantially in accordance with Fig. 32.