FORM 2
THE PATENTS ACT 1970
(Act 39 of 1970)
COMPLETE SPECIFICATION
(SECTION 10, rule 13)
"ESOMEPRAZOLE STRONTIUM SALT, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING
SAME"
Glenmark Pharmaceuticals Limited an Indian Company, registered under the Indian company's Act 1957 and having
its registered office at
Glenmark House,
HDO - Corporate Bldg, Wing -A,
B.D. Sawant Marg, Chakala, Andheri (East), Mumbai - 400 099
THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED

1

PRIORITY
[0001] This application claims the benefit under Indian Provisional Application No.
564/MUM/2005, filed May 6, 2005, and entitled "ESOMEPRAZOLE STRONTIUM SALT", the contents of each of which are incorporated by reference herein.
BACKGROUND OF THE INVENTION
1. Technical Field
[0002] The present invention generally relates to a novel strontium salt of
esomeprazole, a process for its preparation and pharmaceutical compositions containing same.
2. Description of the Related Art
[0003] Omeprazole (also known as 5-methoxy-2-[|(4-methoxy-3,5-dimethyl-2-
pyridyl)methyl]-sulfinyl]-lH-benzimidazole) is a well known compound used for treating diseases related to increased secretion of gastric acid because of an H+/K+ ATPase inhibitory action. The compound, being a sulfoxide, has an asymmetric center in the sulfur atom and may exist as a racemic mixture (a mixture of (R)-omeprazole and (S)-omeprazole). The optical isomers of omeprazole, particularly the (S) isomer, are believed to possess certain advantages over the racemic form.
[0004] The enantiomer (S)-omeprazole is commonly referred to as esomeprazole (also
known as (5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]-sulfinyl]-lH-benzimidazole-1-yl) and is represented by the structure of formula I.

Esomeprazole is marketed in the United as States the magnesium trihydrate salt under the name Nexium® and is indicated for short-term treatment in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis. See, e.g., The. Merck Index,
2

Thirteenth Edition, 2001, pp. 1224-25, monograph 6913; and Physician's Desk Reference,
"Nexium," 60th Edition, pp. 645-649 (2005).
[0005] U.S. Patent No. 4,738,974, herein incorporated by reference, discloses the
lithium, sodium, potassium, magnesium and calcium salts of omeprazole.
[0006] U.S. Patent No. 5,693,818, herein incorporated by reference, discloses
optically pure salts of esomeprazole, such as sodium, potassium, lithium, magnesium, calcium
and tetraalkylammonium salts.
[0007] Different forms of an active principle can have different bioavailability,
solubility, stability, color, compressibility, flow ability and workability with consequent
modification of the profiles of toxicological safety, clinical effectiveness and productive
efficiency. Because improved drug formulations showing, for example, better bioavailability
or better stability are consistently sought, there is an ongoing need for new or purer forms of
existing drug molecules.
SUMMARY OF THE INVENTION
[0008] In accordance with one embodiment of the present invention, a strontium salt
of esomeprazole or a derivative thereof is provided.
[0009] In accordance with a second embodiment of the present invention, a process
for preparing a strontium salt of esomeprazole is provided comprising reacting esomeprazole
free base or a sodium, potassium or lithium salt of esomeprazole with a strontium source in
one or more solvents.
[0010] In accordance with a third embodiment of the present invention, a
pharmaceutical composition is provided comprising a therapeutically effective amount of a
strontium salt of esomeprazole.
[0011] In accordance with a fourth embodiment of the present invention, a method for
treating a gastric acid related condition is provided, the method comprising administering to a
subject in need of treatment thereof a therapeutically effective amount of a strontium salt of
esomeprazole.
3

DEFINITIONS
[0012] The term "HPLC" as used herein means high performance liquid
chromatograpy, and "e.e." as used herein means enantiomeric excess.
[0013] The term "treating" or "treatment" of a state, disorder or condition as used
herein means: (1) preventing or delaying the appearance of clinical symptoms of the state,
disorder or condition developing in a mammal that may be afflicted with or predisposed to the
state, disorder or condition but does not yet experience or display clinical or subclinical
symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition,
i.e., arresting or reducing the development of the disease or at least one clinical or subclinical
symptom thereof, or (3) relieving the disease, i.e., causing regression of the state, disorder or
condition or at least one of its clinical or subclinical symptoms. The benefit to a subject to be
treated is either statistically significant or at least perceptible to the patient or to the physician.
[0014] The term "therapeutically effective amount" as used herein means the amount
of a compound that, when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.
[0015] The term "delivering" as used herein means providing a therapeutically
effective amount of an active ingredient to a particular location within a host means causing a therapeutically effective blood concentration of the active ingredient at the particular location. This can be accomplished, e.g., by topical, local or by systemic administration of the active ingredient to the host.
[0016] The term "buffering agent" as used herein means a compound used to resist a
change in pH upon dilution or addition of acid of alkali. Such compounds include, by way of example and without limitation, potassium metaphosphate, potassium phosphate, monobasic sodium acetate and sodium citrate anhydrous and dehydrate and other such material known to those of ordinary skill in the art.
[0017] The term "sweetening agent" as used herein means a compound used to impart
sweetness to a preparation. Such compounds include, by way of example and without
4

limitation, aspartame, dextrose, glycerin, mannitol, saccharin sodium, sorbitol, sucrose,
fructose and other such materials known to those of ordinary skill in the art.
[0018] The term "binders" as used herein means substances used to cause adhesion of
powder particles in tablet granulations. Such compounds include, by way of example and without limitation, acacia alginic acid, tragacanth, carboxymethylcellulose sodium, poly (vinylpyrrolidone), compressible sugar (e.g., NuTab), ethylcellulose, gelatin, liquid glucose, methylcellulose, povidone and pregelatinized starch, combinations thereof and other material known to those of ordinary skill in the art.
[0019] When needed, other binders may also be included in the present invention.
Exemplary binders include starch, poly(ethylene glycol), guar gum, polysaccharide, bentonites, sugars, invert sugars, poloxamers (PLURONIC™ F68, PLURONIC™ F127), collagen, albumin, celluloses in nonaqueous solvents, combinations thereof and the like. Other binders include, for example, poly(propylene glycol), polyoxyethylene-polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, poly(ethylene oxide), microcrystalline cellulose, poly(vinylpyrrolidone), combinations thereof and other such materials known to those of ordinary skill in the art.
[0020] The term "diluent" or "filler" as used herein means inert substances used as
fillers to create the desired bulk, flow properties, and compression characteristics in the preparation of tablets and capsules. Such compounds include, by way of example and without limitation, dibasic calcium phosphate, kaolin, sucrose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sorbitol, starch, combinations thereof and other such materials known to those of ordinary skill in the art.
[0021] The term "glidant" as used herein means agents used in tablet and capsule
formulations to improve flow-properties during tablet compression and to produce an anti-
caking effect. Such compounds include, by way of example and without limitation, colloidal
silica, calcium silicate, magnesium silicate, silicon hydrogel, cornstarch, talc, combinations
thereof and other such materials known to those of ordinary skill in the art.
[0022] The term "lubricant" as used herein means substances used in tablet
formulations to reduce friction during tablet compression. Such compounds include, by way
5

of example and without limitation, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, combinations thereof and other such materials known to those of ordinary skill in the art.
[0023] The term "disintegrant" as used herein means a compound used in solid dosage
forms to promote the disruption of the solid mass into smaller particles which are more readily dispersed or dissolved. Exemplary disintegrants include, by way of example and without limitation, starches such as corn starch, potato starch, pre-gelatinized and modified starched thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose (e.g. Avicel™), carsium (e.g. Amberlite™), alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, tragacanth, combinations thereof and other such materials known to those of ordinary skill in the art.
[0024] The term "wetting agent" as used herein means a compound used to aid in
attaining intimate contact between solid particles and liquids. Exemplary wetting agents include, by way of example and without limitation, gelatin, casein, lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers (e.g., macrogol ethers such as cetomacrogol 1000), polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, (e.g., TWEEN™s), polyethylene glycols, polyoxyethylene stearates colloidal silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxyl propylcellulose, hydroxypropylmethylcellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, and polyvinylpyrrolidone (PVP). Tyloxapol (a nonionic liquid polymer of the alkyl aryl polyether alcohol type, also known as superinone or triton) is another useful wetting agent, combinations thereof and other such materials known to those of ordinary skill in the art.
[0025] Most of these excipients are described in detail in, e.g., Howard C. Ansel et al.,
Pharmaceutical Dosage Forms and Drug Delivery Systems, (7th Ed. 1999); Alfonso R. Gennaro et al., Remington: The Science and Practice of Pharmacy, (20th Ed. 2000); and A.
6

Kibbe, Handbook of Pharmaceutical Excipients, (3rd Ed. 2000), which are incorporated by reference herein.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0026] The present invention is directed to a strontium salt of esomeprazole. The
esomeprazole strontium salt can be of any form and can be obtained by at least reacting esomeprazole in its free base form or as a sodium, potassium or lithium salt of esomeprazole with a strontium source in a suitable solvent. Another aspect of the present invention provides a substantially pure strontium salt of esomeprazole. In one embodiment, a strontium salt of esomeprazole has a purity of greater than or equal to about 95%. In another embodiment, a strontium salt of esomeprazole has a purity of greater than or equal to about 98%. In yet another embodiment, a strontium salt of esomeprazole has a purity of greater than or equal to about 99%.
[0027] The esomeprazole free base or a sodium, potassium or lithium salt of
esomeprazole to be used in the preparation of a strontium salt of esomeprazole of the present invention is well known and can be obtained by processes known in the art. See, e.g., U. S. Patent Nos. 5,693,818; 5,948,789 and 6,162,816 and international Patent Application Nos. WO 92/08716, WO 98/54171 and WO 00/44744, the contents of each of which are incorporated by reference herein.
[0028] Suitable sources of strontium to react with the esomeprazole free base or a
sodium, potassium or lithium salt of esomeprazole include, but are not limited to, inorganic acid salts of strontium, organic acid salts of strontium, and the like and combinations thereof. Suitable inorganic acid salts of strontium for use in the process of the present invention include, but are not limited to, strontium chloride, strontium chloride hexahydrate, strontium nitrate, strontium bromide, strontium sulfate, strontium carbonate and the like and mixtures thereof. Suitable organic acid salts of strontium for use in the process of the present invention include, but are not limited to, strontium acetate, strontium isopropoxide, strontium oxalate, strontium tartrate and strontium succinate and the like and mixtures thereof. The amount of
7

the strontium source will ordinarily range from about 1 molar equivalent to about 5 molar equivalents per molar equivalent of esomeprazole starting material.
[0029] Soluble solvents for use herein include any solvent or solvent mixture in which
the esomeprazole free base or salt is soluble. Representative examples of such solvents
include, but are not limited to, water, alcohols, ketones, cyclic ethers, chlorinated
hydrocarbons, nitriles, dipolar aprotic solvents and the like, and mixture thereof. Examples of
alcohols include methanol, ethanol, isopropanol and the like. Examples of ketones include
acetone, methyl isobutyl ketone and the like. Examples of cyclic ethers include
tetrahydrofuran, dioxane and the like. Examples of chlorinated hydrocarbons include
methylene dichloride, ethylene dichloride and the like. Examples of nitriles include
acetonitrile and the like. Examples of dipolar aprotic solvents include dimethylsulfoxide,
dimethylformamide and the like. Mixtures of all of these solvents are also contemplated.
[0030] In general, the reaction can be carried out at a suitable temperature and for a
sufficient period of time to form a strontium salt of esomeprazole. A suitable temperature will ordinarily range from about 0°C to about 50°C. In one embodiment, the temperature is an elevated temperature. In another embodiment, the temperature is room temperature. The time period can range from about 30 minutes to about 15 hours.
[0031] In one embodiment, the reaction involves reacting a first solvent solution
containing at least esomeprazole free base or a sodium, potassium or lithium salt of esomeprazole and a first solvent with a second solvent solution containing at least a strontium source and a second solvent. The first and second solvents can be any of the aforementioned solvents. In one embodiment, the first and second solvents are the same. In another embodiment, the first and second solvents are different.
[0032] Following the reaction, the strontium salt of esomeprazole thus obtained is
isolated and recovered. For example, when carrying out the reaction in a solvent which the reactants are relatively more soluble than the strontium salt of esomeprazole, e.g., water, the strontium salt forming reaction will be accompanied by a spontaneous precipitation out of solution of the esomeprazole strontium salt. The precipitated esomeprazole strontium salt can
8

then be recovered by conventional techniques, e.g., filtration or centrifugation, optionally followed by washing and/or drying.
[0033] In another way of isolating strontium salt of esomeprazole, precipitation of the
esomeprazole strontium salt may be facilitated by evaporating the solvent and/or by adding an anti solvent to the solution in the case where the solvent employed is a solvent in which the esomeprazole strontium salt is insoluble or sparingly soluble. In another embodiment, precipitation can also be induced by cooling the solution to a temperature sufficient to precipitate a solid of esomeprazole strontium salt, especially if the initial temperature during addition of the reactants is elevated. The precipitated esomeprazole strontium may then be recovered in a solid state by conventional techniques, e.g., filtration or centrifugation, optionally followed by washing and/or drying.
[0034] Suitable anti solvents that may be added to precipitate out a strontium salt of
esomeprazole include, but are not limited to, lower alkyl ethers such as diethyl ether, diisopropyl ether and the like and mixtures thereof.
[0035] Yet another aspect of the present invention is directed to pharmaceutical
compositions containing at least the novel strontium salt of esomeprazole of the present invention. Such pharmaceutical compositions may be administered to a mammalian patient in any dosage form, e.g., liquid, powder, elixir, injectable solution, etc. Dosage forms may be adapted for administration to the patient by oral, buccal, parenteral, ophthalmic, rectal and transdermal routes or any other acceptable route of administration. Oral dosage forms include, but are not limited to, tablets, pills, capsules, troches, sachets, suspensions, powders, lozenges, elixirs and the like. The novel strontium salt of esomeprazole of the present invention also may be administered as suppositories, ophthalmic ointments and suspensions, and parenteral suspensions, which are administered by other routes. The dosage forms may contain the novel strontium salt of esomeprazole of the present invention as is or, alternatively, may contain the novel strontium salt of esomeprazole as part of a composition. The pharmaceutical compositions may further contain one or more pharmaceutically acceptable excipients. Suitable excipients and the amounts to use may be readily determined by the formulation scientist based upon experience and consideration of standard procedures
9

and reference works in the field, e.g., the buffering agents, sweetening agents, binders,
diluents, fillers, lubricants, wetting agents and disintegrants described hereinabove.
[0036] Capsule dosages will contain the novel strontium salt of esomeprazole of the
present invention within a capsule which may be coated with gelatin. Tablets and powders may also be coated with an enteric coating. The enteric-coated powder forms may have coatings comprising phthalic acid cellulose acetate, hydroxypropylmethyl cellulose phthalate, polyvinyl alcohol phthalate, carboxy methyl ethyl cellulose, a copolymer of styrene and maleic acid, a copolymer of methacrylic acid and methyl methacrylate, and like materials, and if desired, they may be employed with suitable plasticizers and/or extending agents. A coated capsule or tablet may have a coating on the surface thereof or may be a capsule or tablet comprising a powder or granules with an enteric-coating.
[0037] Tableting compositions may have few or many components depending upon
the tableting method used, the release rate desired and other factors. For example, the compositions of the present invention may contain diluents such as cellulose-derived materials like powdered cellulose, microcrystalline cellulose, microfine cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose salts and other substituted and unsubstituted celluloses; starch; pregelatinized starch; inorganic diluents such calcium carbonate and calcium diphosphate and other diluents known to one of ordinary skill in the art. Yet other suitable diluents include waxes, sugars (e.g. lactose) and sugar alcohols like mannitol and sorbitol, acrylate polymers and copolymers, as well as pectin, dextrin and gelatin.
[0038] Other excipients contemplated by the present invention include binders, such
as acacia gum, pregelatinized starch, sodium alginate, glucose and other binders used in wet and dry granulation and direct compression tableting processes; disintegrants such as sodium starch glycolate, crospovidone, low-substituted hydroxypropyl cellulose and others; lubricants like magnesium and calcium stearate and sodium stearyl fumarate; flavorings; sweeteners; preservatives; pharmaceutically acceptable dyes and glidants such as silicon dioxide.
10

[0039] In one embodiment, the novel strontium salt of esomeprazole for use in the
pharmaceutical compositions of the present invention can have a D50 and D90 particle size of less than about 400 microns, preferably less than about 200 microns, more preferably less than about 150 microns, still more preferably less than about 50 microns and most preferably less than about 15 microns. The term "micronization" used herein means any process or methods by which the size of the particles is reduced. For example, the particle sizes of the novel strontium salt of esomeprazole can be obtained by any milling, grinding, micronizing or other particle size reduction method known in the art to bring the solid state form of the novel strontium salt of esomeprazole of the present invention into any of the foregoing desired particle size range. As also used herein, esomeprazole strontium salt particles with reduced size are referred to as "micronized particles of esomeprazole strontium salt" or "micronized esomeprazole strontium salt".
[0040] The esomeprazole strontium salt of the present invention may be used for
inhibiting gastric acid secretion in mammals. In a more general sense, the esomeprazole strontium salt of the present invention may be used for the treatment of gastric acid-related diseases and gastrointestinal inflammatory diseases in mammals such as, for example, gastric ulcer, duodenal ulcer, reflux esophagitis, and gastritis. Furthermore, the esomeprazole strontium salt may be used for treatment of other gastrointestinal disorders where gastric antisecretory effect is desirable, e.g., in patients on NSAID therapy, in patients with gastrinomas, and in patients with accute upper gastrointestinal bleeding. The esomeprazole strontium salt may also be used in patients in intensive care situations, and pre- and postoperatively to prevent acid aspiration and stress ulceration. The esomeprazole strontium salt may also be used for treatment or prophylaxis of inflammatory conditions in mammals, including man, especially those involving lysozymal enzymes. Conditions that may be specifically mentioned are rheumatoid arthritis and gout. The esomeprazole strontium salt of the present invention may also be useful in the treatment of psoriasis as well as in the treatment of Helicobacter infections.
[0041] Actual dosage levels of the novel strontium salt of esomeprazole of the present
invention may be varied to obtain an amount that is effective to obtain a desired therapeutic
11

response for a particular composition and method of administration for treatment of a
mammal. The selected dosage level therefore depends upon such factors as, for example, the
desired therapeutic effect, the route of administration, the desired duration of treatment, and
other factors. The total daily dose of the novel strontium salt of esomeprazole of the present
invention can be administered to a host in single or divided dose and can vary widely
depending upon a variety of factors including, for example, the body weight, general health,
sex, diet, time and route of administration, rates of absorption and excretion, combination
with other drugs, the severity of the particular condition being treated, etc.
[0042] The following examples are provided to enable one skilled in the art to practice
the invention and are merely illustrative of the invention. The examples should not be read as limiting the scope of the invention as defined in the features and advantages.
EXAMPLE 1
[0043] Preparation of esomeprazole strontium salt
[0044] The potassium salt of esomeprazole (5 g) was dissolved in water (100 ml) at
room temperature and a solution of strontium chloride hexahydrate (5 g) dissolved in water (100 ml) was slowly added. The reaction mixture was stirred at room temperature for about 1 to about 2 hours. The solids that precipitated were filtered and the wet cake was washed with water (25 ml). The wet cake was air dried at a temperature ranging from about 40°C to about 45°C to provide esomeprazole strontium salt (4.2 g). (HPLC Purity > 99.6%, > 99.5% enantiomeric excess (ee)).
EXAMPLE 2
[0045] Preparation of esomeprazole strontium salt
[0046] The sodium salt of esomeprazole (5 g) was dissolved in water (100 ml) at room
temperature and a solution of strontium chloride hexahydrate (5 g) dissolved in water (100 ml) was slowly added. The reaction mixture was stirred at room temperature for about 1 to about 2 hours. The solids that precipitated were filtered and the wet cake was washed with
12

water (25 ml). The wet cake was air dried at a temperature ranging from about 40°C to about 45°C to provide esomeprazole strontium salt (4.8 g). (HPLC Purity > 99.3%, > 99.8% ee).
EXAMPLE 3
[0047] Preparation of esomeprazole strontium salt
[0048] Esomeprazole free base (5 g) was dissolved in isopropanol (50 ml) at room
temperature and a solution of strontium isopropoxide (5 g) dissolved in isopropanol (50 ml) was slowly added. The reaction mixture was stirred at room temperature for about 1 to about 2 hours and the reaction mass was quenched in water. The precipitated solids were filtered and the wet cake was washed with water (25 ml). The wet cake was air dried at a temperature ranging from about 40°C to about 45°C to provide esomeprazole strontium salt (4.0 g). (HPLC Purity > 98.9%, > 99.7% ee).
[0049] It will be understood that various modifications may be made to the
embodiments disclosed herein. Therefore the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the present invention are for illustration purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the features and advantages appended hereto.
13

WE CLAIM:
1. A process for preparing a strontium salt of esomeprazole, the process comprising
reacting esomeprazole free base or a sodium, potassium or lithium salt of esomeprazole with a
strontium source in one or more solvents.
2. The process of Claim 1, comprising reacting esomeprazole free base with a
strontium source in one or more solvents.
3. The process of Claim 1, comprising reacting a sodium salt of esomeprazole with a strontium source in one or more solvents.
4. The process of Claim 1, comprising reacting a potassium salt of esomeprazole with a strontium source in one or more solvents.
5. The process of Claim 1, comprising reacting a lithium salt of esomeprazole with a strontium source in one or more solvents.
6. The process of Claims 1-5, wherein the strontium source is selected from the group consisting of an inorganic acid salt of strontium, organic acid salt of strontium and mixtures thereof.
7. The process of Claims 1-6, wherein the strontium source is selected from the group consisting of strontium chloride, strontium chloride hexahydrate, strontium isopropoxide, strontium nitrate, strontium bromide, strontium sulfate, strontium carbonate, strontium acetate, strontium oxalate, strontium tartrate, strontium succinate and mixtures thereof.
8. The process of Claims 1-7, wherein the amount of the strontium source is from about 1 to about 5 molar equivalents per molar equivalent of the esomeprazole free base or the sodium, potassium or lithium salt of esomeprazole.
14

9. The process of Claims 1-8, wherein the solvent is selected from the group consisting of water, C1-C10 alcohol, Ci-Cio ketone, Ci-Cio cyclic ether, chlorinated hydrocarbon, nitrile, dipolar aprotic solvent and mixtures thereof.
10. The process of Claims 1-8, wherein the solvent comprises water.
11. The process of Claims 1-8, wherein the solvent comprises an alcohol selected
from the group consisting of methanol, ethanol, isopropanol, and mixtures thereof.
12. The process of Claims 1-11, wherein the reaction is carried out at room
temperature.
13. The process of Claims 1-11, wherein the reaction is carried out at an elevated temperature.
14. The process of Claims 1-13, further comprising precipitating the strontium salt of esomeprazole and recovering the strontium salt of esomeprazole.
15. The process of Claims 1-8, comprising reacting a first solvent solution comprising esomeprazole free base or a sodium, potassium or lithium salt of esomeprazole and a first solvent with a second solvent solution comprising a strontium source and a second solvent.
16. The process of Claim 15, wherein the first and second solvent are the same.
17. The process of Claims 15 and 16, wherein the first and second solvent are water or an alcohol.
18. The process of Claim 15, wherein the first and second solvent are water or
isopropanol.
15

19. The process of Claim 15, wherein the first and second solvent are different.
20. The process of Claims 15-19, further comprising precipitating the strontium salt of esomeprazole and recovering the strontium salt of esomeprazole.
21. The process of Claim 20, wherein the step of precipitating the strontium salt of esomeprazole comprises evaporating the solvent.
22. The process of Claim 20, wherein the step of precipitating the strontium salt of esomeprazole comprises adding an anti solvent to the reaction solution.
23. The process of Claim 22, wherein the anti solvent is a lower alkyl ether.

24. The process of Claims 1-19, further comprising isolating the strontium salt of esomeprazole comprising evaporating the solvent.
25. The process of Claims 1-19, further comprising isolating the strontium salt of esomeprazole comprising adding an anti solvent to the reaction solution.
26. The process of Claim 25, wherein the anti solvent is a lower alkyl ether.
27. The process of Claims 1-26, wherein the strontium salt of esomeprazole has a purity of greater than or equal to about 95%.
28. The process of Claims 1-26, wherein the strontium salt of esomeprazole has a purity of greater than or equal to about 98%.
29. The process of Claims 1-26, wherein the strontium salt of esomeprazole has a purity of greater than or equal to about 99%.
16

30. The process of Claims 1-26, wherein the strontium salt of esomeprazole has an enantiomeric excess of greater than or equal to about 95%.
31. The process of Claims 1-26, wherein the strontium salt of esomeprazole has an enantiomeric excess of greater than or equal to about 98%.
32. The process of Claims 1-26, wherein the strontium salt of esomeprazole has an enantiomeric excess of greater than or equal to about 99%.
33. A strontium salt of esomeprazole prepared by the process of Claims 1-32.
34. A strontium salt of esomeprazole or a derivative thereof.
35. Substantially pure strontium salt of esomeprazole.
36. The strontium salt of esomeprazole of Claim 35, having a purity of greater than or equal to about 95%.
37. The strontium salt of esomeprazole of Claim 35, having a purity of greater than or equal to about 98%.
38. The strontium salt of esomeprazole of Claim 35, having a purity of greater than or equal to about 99%.

39. The strontium salt of esomeprazole of Claims 34-38, having an enantiomeric excess of greater than or equal to about 95%.
40. The strontium salt of esomeprazole of Claims 34-38, having an enantiomeric excess of greater than or equal to about 98%.
17

41. The strontium salt of esomeprazole of Claims 34-38, having an enantiomeric excess of greater than or equal to about 99%.
42. A pharmaceutical composition comprising a therapeutically effective amount of the strontium salt of esomeprazole of Claims 33 -41.
43. The pharmaceutical composition of Claim 42, wherein the strontium salt of esomeprazole is a micronized strontium salt of esomeprazole having a particle size of less than about 400 microns.
44. The pharmaceutical composition of Claim 42, wherein the strontium salt of esomeprazole is a micronized strontium salt of esomeprazole having a particle size of less than about 200 microns.
45. The pharmaceutical composition of Claim 42, wherein the strontium salt of esomeprazole is a micronized strontium salt of esomeprazole having a particle size of less than about 150 microns.

46. The pharmaceutical composition of Claim 42, wherein the strontium salt of esomeprazole is a micronized strontium salt of esomeprazole having a particle size of less than about 50 microns.
47. The pharmaceutical composition of Claim 42, wherein the strontium salt of esomeprazole is a micronized strontium salt of esomeprazole having a particle size of less than about 15 microns.
48. The pharmaceutical composition of Claims 42-47, further comprising one or more
pharmaceutically acceptable excipients.
18

49. The pharmaceutical composition of Claims 42-48, in solid form.
50. The pharmaceutical composition of Claims 42-49, which is in the form of a tablet or capsule.
51. A method for treating a gastric acid related condition, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a strontium salt of esomeprazole of Claims 33-41.
52. Use of a strontium salt of esomeprazole of Claims 33-41 in the manufacture of a medicament for use in the treatment of a gastric acid related condition.

19