WO2005082888A1 - Process for the preparation of magnesium salt of omeprazole - Google Patents
Process for the preparation of magnesium salt of omeprazole Download PDFInfo
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- WO2005082888A1 WO2005082888A1 PCT/TR2004/000014 TR2004000014W WO2005082888A1 WO 2005082888 A1 WO2005082888 A1 WO 2005082888A1 TR 2004000014 W TR2004000014 W TR 2004000014W WO 2005082888 A1 WO2005082888 A1 WO 2005082888A1
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- Prior art keywords
- omeprazole
- process according
- magnesium
- magnesium hydroxide
- hydroxide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the present -invention relates to a novel process in general for the preparation of water insoluble salts of substituted benzimidazoles and more particularly for the preparation of magnesium salt of the anti-ulcer agent omeprazole.
- Substituted benzimidazoles such as the compounds with the generic names omeprazole, lansoprazole, pantoprazole, rabepazole, pariprazole leminoprazole and esomeprazole (single enantiomer of omeprazole) known as proton pump inhibitors and have properties making the compounds useful as inhibitors of H + K + ATPase inhibitors.
- the magnesium salt of acid pump inhibitors and especially of omeprazole compound is highly appropriate for preparing pharmaceutical formulations such as tablets. Due to the stability of the magnesium salts, they can be easily purified by crystallization and can be treated with pharmaceutical procedures and processes.
- omeprazole whose chemical formula is 5- methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H-benzimidazole is an gastric acid pump inhibitor and used for treatment of gastric and duodenal ulcers, gastritis and reflux esophagitis.
- the omeprazole compound is defined in European Patent no 5129
- the present • invention relates to a novel process in general for the preparation of water insoluble salts of substituted benzimidazoles and more particularly for the preparation of magnesium salt of the anti-ulcer agent omeprazole.
- Substituted benzimidazoles such as the compounds with the generic names omeprazole, lansoprazole, pantoprazole, rabepazole, pariprazole leminoprazole and esomeprazole (single enantiomer of omeprazole) known as proton pump inhibitors and have properties making the compounds useful as inhibitors of H + K + ATPase inhibitors.
- the magnesium salt of acid pump inhibitors and especially of omeprazole compound is highly appropriate for preparing pharmaceutical formulations such as tablets. Due to the stability of the magnesium salts, they can be easily purified by crystallization and can be treated with pharmaceutical procedures and processes.
- omeprazole whose chemical formula is 5- methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H-benzimidazole is an gastric acid pump inhibitor and used for treatment of gastric and duodenal ulcers, gastritis and reflux esophagitis.
- the omeprazole compound is defined in European Patent no 5129
- magnesium hydroxide which is poorly soluble and is normally difficult to be removed from the final product and therefore is undesirable even as by product during the process, can not be eliminated or to minimize its precipitation during the process a weak base should be used besides a magnesium source.
- the object of the present invention is to provide a process for the preparation of magnesium omeprazole with high purity that differs from the known processes in the prior art.
- the novel process is carried out by directly treatment of magnesium hydroxide which is used as magnesium source with omeprazole.
- the present invention discloses the process, where magnesium hydroxide, which is an inorganic weak base and used as magnesium source, is directly reacted with omeprazole.
- the magnesium source is magnesium hydroxide which is a poorly soluble inorganic magnesium salt. Unreacted little amount of magnesium hydroxide is separated off easily by using suitable equipments, such as centrifuge or nuche and is ' not required any special condition.
- the novel process for the manufacture of magnesium omeprazole is characterized by the following four consecutive steps: a) treating omeprazole with magnesium hydroxide, which is an inorganic magnesium source, in a solution, b) removing the unreacted magnesium hydroxide from the reaction mixture, c) crystallizing magnesium omeprazole, and d) purifying by washing with ethylacetate
- magnesium omeprazole in tetrahydrofuran is similar to methanol. Magnesium omeprazole is highly soluble in both of these solvents, especially in methanol. Magnesium hydroxide is insoluble in both of these solvents. Since magnesium omeprazole can be easily crystallised from the mixture of tetrahydrofuran and cyclohexan, firstly the product is formed by crystallization. But the product crystallised from the mixture also contains unreacted magnesium hydroxide.
- methanol is added because of the excellent solubility of magnesium omeprazole in methanol. Unreacted magnesium hydroxide can be removed easily by filtration since it is insoluble in methanol.
- the third step water is added for recrystallization of magnesium omeprazole and some of the methanol is removed by distillation to ensure the crystallizing conditions.
- the product is purified by washing with ethylacetate to remove the remaining small amount of unreacted materials. This clarification can be clearly observed with disappearing of the slight colour pf product and appearing of the slightly coloured filtrate.
- magnesium hydroxide 0.5-1.5 mole equivalent, preferably 0.9-1.1 mole equivalent or 1 mole of magnesium hydroxide is treated with Omeprazole in an ether, preferably tetrahydrofurane which is enough to dissolve Omeprazole completely (1 unit of omeprazole in weight/8-12 units of tetrahydrofurane in weight) at ambient temperature.
- the reacted magnesium hydroxide may be either in solid form or %10-50 aqueous solution.
- a hydrocarbon preferably cyclohexan (1 unit of omeprazole in weight/ 2-5 unit of cyclohexan in weight
- the solvents are evaporated to dryness (till no solvent is remained) by increasing the heat to 30-45 °C.
- magnesium omeprazole is highly soluble in methanol
- the sufficient amount of alcohol to dissolve the remained crystals after distillation preferably methanol (1 unit of Omeprazole in weight / 14-17 unit of methanol in weight) is added and the product is dissolved at 20-35 °C.
- the excess amount of magnesium hydroxide does not dissolve.
- activated charcoal is added. The mixture is stirred for 20-40 minutes and the unreacted magnesium hydroxide is removed by filtration.
- Water equal to amount of the methanol or less preferably half of it, is added to the solution and the crystallization is started by means of evaporating 60 % - 90 % of initial volume.
- the temperature of the solution is lowered to 0 - 30 °C and it is stirred until the crystallization is completed.
- the crystallized product is separated via centrifugation or filtration.
- the crystals is washed with water and dried at 50- 75 °C.
- the almost dry product is treated with ethyl acetate to remove small amount of unreacted materials and it is filtered. Finally, the product is washed with ethyl acetate and dried at 40-50 °C.
- the water content of the magnesium omeprazole is 8- 12 % at the end of the process.
- 0.5-1.5 mole equivalent, preferably 0.9-1.1 or 1 mole equivalent of magnesium hydroxide is used for 1 mole omeprazole and unreacted magnesium hydroxide can be easily removed.
- the final product, magnesium omeprazole can be obtained with high yield (90 % and more than 90%) and with high purity.
- the subject process of the invention can be used for preparation of magnesium salts of " subtituted benzimidazols such as lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole.
- subtituted benzimidazols such as lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole.
- the subject process of the invention can also be used for preparation of calcium salts of subtituted benzimidazols such as lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole ' .
- subtituted benzimidazols such as lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole ' .
- the synthesis procedure of calcium omeprazole is the same as magnesium omeprazole synthesis.
- magnesium hydroxide 0.5-1.5 mol equivalent, preferably 0.9-1.1 mol equivalent to calcium hydroxide with a similar solubility is reacted with omeprazole.
- the alcohol preferably ethanol is used to remove the excess amount of calcium hydroxide because calcium omeprazole is more soluble in ethanol than methanol.
Abstract
The present invention relates to a novel process for the preparation of magnesium salt of omeprazole which is used as active ingredient in pharmaceutical industry. The process discloses direct treatment of omeprazole with magnesium hydroxide that is a weak inorganic base as magnesium source. By this invention, the difficulties caused by magnesium hydroxide that is formed during omeprazole magnesium salt preparation can be eliminated and omeprazole magnesium can be obtained with high yield and high purity.
Description
PROCESS FOR THE PREPARATION OF MAGNESIUM SALT OF OMEPRAZOLE
DESCRIPTION
FIELD OF THE INVENTION
The present -invention relates to a novel process in general for the preparation of water insoluble salts of substituted benzimidazoles and more particularly for the preparation of magnesium salt of the anti-ulcer agent omeprazole.
BACKGROUND OF THE INVENTION
Substituted benzimidazoles such as the compounds with the generic names omeprazole, lansoprazole, pantoprazole, rabepazole, pariprazole leminoprazole and esomeprazole (single enantiomer of omeprazole) known as proton pump inhibitors and have properties making the compounds useful as inhibitors of H+K+ATPase inhibitors.
For the well-known status of the technique, the magnesium salt of acid pump inhibitors and especially of omeprazole compound is highly appropriate for preparing pharmaceutical formulations such as tablets. Due to the stability of the magnesium salts, they can be easily purified by crystallization and can be treated with pharmaceutical procedures and processes.
For the well-known status of the technique, omeprazole whose chemical formula is 5- methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H-benzimidazole is an gastric acid pump inhibitor and used for treatment of gastric and duodenal ulcers, gastritis and reflux esophagitis. The omeprazole compound is defined in European Patent no 5129
(Haessle AB) while particular alkaline salts of the compound is defined in European Patent No 124495 (Haessle AB).
There is a - general need in pharmaceutical industry that pharmaceutically active compounds should be produced by processes giving products with properties making them suitable for pharmaceutical preparations. Therefore many processes have been disclosed for obtaining omeprazole and it's therapeutically acceptable salts, in order to develop more efficient processes. Some of them are American patents US6048981 (Torcan Chemical Ltd.), US6166213 ( erck& Co. Inc.), US6369085 (Astra Zeneca AB)
PROCESS FOR THE PREPARATION OF MAGNESIUM SALT OF OMEPRAZOLE
DESCRIPTION
FIELD OF THE INVENTION
The present •invention relates to a novel process in general for the preparation of water insoluble salts of substituted benzimidazoles and more particularly for the preparation of magnesium salt of the anti-ulcer agent omeprazole.
BACKGROUND OF THE INVENTION
Substituted benzimidazoles such as the compounds with the generic names omeprazole, lansoprazole, pantoprazole, rabepazole, pariprazole leminoprazole and esomeprazole (single enantiomer of omeprazole) known as proton pump inhibitors and have properties making the compounds useful as inhibitors of H+K+ATPase inhibitors.
For the well-known status of the technique, the magnesium salt of acid pump inhibitors and especially of omeprazole compound is highly appropriate for preparing pharmaceutical formulations such as tablets. Due to the stability of the magnesium salts, they can be easily purified by crystallization and can be treated with pharmaceutical procedures and processes.
For the well-known status of the technique, omeprazole whose chemical formula is 5- methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H-benzimidazole is an gastric acid pump inhibitor and used for treatment of gastric and duodenal ulcers, gastritis and reflux esophagitis. The omeprazole compound is defined in European Patent no 5129
(Haessle AB) while particular alkaline salts of the compound is defined in European Patent No 124495 (Haessle AB).
There is a - general need in pharmaceutical industry that pharmaceutically active compounds should be produced by processes giving products with properties making them suitable for pharmaceutical preparations. Therefore many processes have been disclosed for obtaining omeprazole and it's therapeutically acceptable salts, in order to develop more efficient processes. Some of them are American patents US6048981 (Torcan Chemical Ltd.), US6166213 (Merck& Co. Inc.), US6369085 (Astra Zeneca AB)
and international applications such as WO95/01977 (Astra Aktiebolag) and W097/41114 (Astra Aktiebolag).
The closest prior art of this novel process is the international application with number WO95/01977 (Astra Aktiebolag) and it discloses a process for the preparation of magnesium salt of omeprazole comprising the following steps; reacting omeprazole with magnesium alcoholate; separating inorganic salts from the reaction mixture and isolating the product via crystallizing the magnesium salt of omeprazole. The magnesium alcoholate is -formed from metallic magnesium, which requires special process conditions. A significant drawback of such method is the constitution of a potential difficulty with the formation of magnesium hydroxide by using of magnesium alcoholate in the process. Filtration of such magnesium hydroxide is complicated because of gelling and extremely small particle size.
The international application W097/41114 discloses improvements over the process disclosed in WO95/01977 for the preparation of the magnesium salts of omeprazole and other substituted benzimidazoles. In this process it is emphasized that there are difficulties originating from the formation of magnesium hydroxide during the reaction and removing it from the end product. It is defined that there should be used a weak base preferably an amine or ammonia besides a magnesium source to minimize the formation of magnesium hydroxide with weak solubility According to the process, preferably magnesium sulphate, nitrate, acetate, chloride, carbonates are used as magnesium source instead of magnesium alcoholate.
By using the processes in the prior art, magnesium hydroxide, which is poorly soluble and is normally difficult to be removed from the final product and therefore is undesirable even as by product during the process, can not be eliminated or to minimize its precipitation during the process a weak base should be used besides a magnesium source.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a process for the preparation of magnesium omeprazole with high purity that differs from the known processes in the prior art. The novel process is carried out by directly treatment of magnesium hydroxide which is used as magnesium source with omeprazole.
DETAILED DESCRIPTION OF THE INVENTION
The present invention discloses the process, where magnesium hydroxide, which is an inorganic weak base and used as magnesium source, is directly reacted with omeprazole.
In such a way, the difficulties to be faced for removing of magnesium hydroxide during the preparation of omeprazole magnesium salt and in the final product can be eliminated and the new process is resulted in a good yield at a high purity of magnesium omeprazole without using any weak organic base. The magnesium source is magnesium hydroxide which is a poorly soluble inorganic magnesium salt. Unreacted little amount of magnesium hydroxide is separated off easily by using suitable equipments, such as centrifuge or nuche and is'not required any special condition.
The novel process for the manufacture of magnesium omeprazole is characterized by the following four consecutive steps: a) treating omeprazole with magnesium hydroxide, which is an inorganic magnesium source, in a solution, b) removing the unreacted magnesium hydroxide from the reaction mixture, c) crystallizing magnesium omeprazole, and d) purifying by washing with ethylacetate
The solubility of omeprazole in tetrahydrofuran is similar to methanol. Magnesium omeprazole is highly soluble in both of these solvents, especially in methanol. Magnesium hydroxide is insoluble in both of these solvents. Since magnesium omeprazole can be easily crystallised from the mixture of tetrahydrofuran and cyclohexan, firstly the product is formed by crystallization. But the product crystallised from the mixture also contains unreacted magnesium hydroxide.
In the second step, methanol is added because of the excellent solubility of magnesium omeprazole in methanol. Unreacted magnesium hydroxide can be removed easily by filtration since it is insoluble in methanol.
In the third step, water is added for recrystallization of magnesium omeprazole and some of the methanol is removed by distillation to ensure the crystallizing conditions.
In the last step, the product is purified by washing with ethylacetate to remove the remaining small amount of unreacted materials. This clarification can be clearly observed with disappearing of the slight colour pf product and appearing of the slightly coloured filtrate.
The process for manufacturing of magnesium omeprazole which is the subject of the invention is described below:
0.5-1.5 mole equivalent, preferably 0.9-1.1 mole equivalent or 1 mole of magnesium hydroxide is treated with Omeprazole in an ether, preferably tetrahydrofurane which is enough to dissolve Omeprazole completely (1 unit of omeprazole in weight/8-12 units of tetrahydrofurane in weight) at ambient temperature. The reacted magnesium hydroxide may be either in solid form or %10-50 aqueous solution. After omeprazole is stirring at 15- 30°C until dissolved completely, a hydrocarbon, preferably cyclohexan (1 unit of omeprazole in weight/ 2-5 unit of cyclohexan in weight), is added to achieve crystallisation.
After stirring at 15-30 °C until the crystallisation is completed, the solvents are evaporated to dryness (till no solvent is remained) by increasing the heat to 30-45 °C. As magnesium omeprazole is highly soluble in methanol, the sufficient amount of alcohol to dissolve the remained crystals after distillation, preferably methanol (1 unit of Omeprazole in weight / 14-17 unit of methanol in weight) is added and the product is dissolved at 20-35 °C. The excess amount of magnesium hydroxide does not dissolve. Then activated charcoal is added. The mixture is stirred for 20-40 minutes and the unreacted magnesium hydroxide is removed by filtration.
Water, equal to amount of the methanol or less preferably half of it, is added to the solution and the crystallization is started by means of evaporating 60 % - 90 % of initial volume. The temperature of the solution is lowered to 0 - 30 °C and it is stirred until the crystallization is completed. The crystallized product is separated via centrifugation or filtration. The crystals is washed with water and dried at 50- 75 °C. The almost dry product is treated with ethyl acetate to remove small amount of unreacted materials and it is filtered. Finally, the product is washed with ethyl acetate and dried at 40-50 °C. The water content of the magnesium omeprazole is 8- 12 % at the end of the process.
Generally, 0.5-1.5 mole equivalent, preferably 0.9-1.1 or 1 mole equivalent of magnesium hydroxide is used for 1 mole omeprazole and unreacted magnesium hydroxide can be easily removed. The final product, magnesium omeprazole can be obtained with high yield (90 % and more than 90%) and with high purity.
Example:
27 kg tetrahydrofurane, 0.5 kg (8.6 mole) magnesium hydroxide (20-30% aqueous solution) and then 3 kg (8.6 mole) omeprazole are charged into a clean reactor. The mixture is stirred at 20-25 °C until it is dissolved completely. After completing the stirring, 10.5 kg of cyclohexan and 30 gr of seed are charged into the reactor and stirred for 15-20 hours at 20-25 °C. At the end of the period the outer temperature is adjusted to 35-40 °C and distilled under vacuum until all the solvent is evaporated. The product is dissolved by adding 47.5 kg of methanol and stirred for about 1 hour at 25-30 °C at the end of the distillation. Undissolved portion is the excess of magnesium hydroxide. At the end of 1 hour, 150 gr of activated charcoal was added to the solution, stirred for 30 minutes at 25- 30 °C and filtered. After charging the filtrate into a clean reactor 21 kg water is added and distilled with vacuum until 35- 40 % of the total volume remains. After the distillation, the temperature is lowered to 20-25 °C and stirred for about 2 hours, the crystallized product is filtrated and washed 3 times with water ( 3 x 3 kg). The product is dried at 60-65 °C until moisture is about 10- 12 %. Then, 13.5 kg ethyl acetate and the product is charged into the clean reactor and filtered after stirring for 1 hour in 20-25 °C, washed two times with ethyl acetate (2 x 2 kg) and finally dried at 40- 50 °C until moisture is 9- 0 %. The yield at the end of the process is about 90%. According to the atomic absorption measurements content for magnesium is 3.33%, while theoretically calculated magnesium content is 3.37%.
The subject process of the invention can be used for preparation of magnesium salts of " subtituted benzimidazols such as lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole.
Alternatively, the subject process of the invention, can also be used for preparation of calcium salts of subtituted benzimidazols such as lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably
esomeprazole'. For example, the synthesis procedure of calcium omeprazole is the same as magnesium omeprazole synthesis. Instead of magnesium hydroxide, 0.5-1.5 mol equivalent, preferably 0.9-1.1 mol equivalent to calcium hydroxide with a similar solubility is reacted with omeprazole.
After the product is crystallized in the mixture tetrahydrofuran and cyclohexan, the alcohol, preferably ethanol is used to remove the excess amount of calcium hydroxide because calcium omeprazole is more soluble in ethanol than methanol.
Claims
What claimed is; 1. A process for the preparation of a magnesium salt of omeprazole represented by the following formula, where a weak inorganic base magnesium hydroxide is directly reacted with omeprazole.
3. A process according to claim 2 wherein omeprazole and magnesium hydroxide are reacted in ether.
4. A process according to claim 3 wherein the said ether is tetrahydrofurane.
5. A process according to claim 3 wherein the reaction temperature is 15-30 °C.
6. A process according to claim 3 wherein 0.5-1.5 mole equivalent of magnesium hydroxide is used for 1 mole omeprazole.
7. A process according to claim 6 wherein 0.9-1.1 mole equivalent of magnesium hydroxide is used for 1 mole of omeprazole.
8. A process according to claim 7 wherein magnesium hydroxide is reacted in solid form.
9. A process according to claim 7 wherein used magnesium hydroxide is 10-50% aqueous solution.
10. A process according to claim 9 wherein used magnesium. hydroxide is 20-30% aqueous solution.
11. A process according to claim 4 wherein the amount of tetrahydrofurane is 8-12 unit in weight per 1 unit in weight of omeprazole.
12. A process according to claim 2 wherein omeprazole and magnesium hydroxide are reacted and followed by crystallisation where hydrocarbon and seeds are used during the crystallisation of magnesium omeprazole which also contains magnesium hydroxide.
13. A process according to claim 12 wherein the said hydrocarbon is cyclohexan.
14. A process according to claim 13 wherein the amount of cyclohexan is 2-5 unit in weight per 1 unit in weight of omeprazole.
15. A process according to claim 12 wherein the crystallisation temperature is 15-30 °C.
16. A process according to claim 2 wherein the crystallisation of magnesium omeprazole containing magnesium hydroxide is followed by distillation under vacuum until no solvent is remained.
17. A process according to claim 16 wherein distillation temperature is 30-45 °C.
18. A process according to claim 2 wherein distillation is followed by separation of magnesium hydroxide from magnesium omeprazole where preferably methanol and active carbon are used.
19. A process according to claim 18 wherein the amount of methanol is 14-17 units in weight per 1 unit in weight of omeprazole.
20. A process according to claim 18 wherein separation is carried out at 20-35 °C.
21. A process according to claim 2 wherein separation of magnesium omeprazole from magnesium hydroxide is followed by removing magnesium hydroxide by filtration.
22. A process according to claim 2 wherein filtration of magnesium hydroxide is followed by water addition to the magnesium omeprazole crystals and distillation under vacuum.
23. A process according to claim 22 wherein the amount of added water is equal to amount of the methanol or less preferably half of it.
24. A process according to claim 22 wherein 60%-90% of the initial volume is evaporated by distillation.
25. A process according to claim 2 wherein crystallisation starts by distillation where 60%-90% of the initial volume evaporates.
26. A process according to claim 25 wherein the solution temperature during the crystallisation is 0-30 °C.
27. A process according to claim 2 wherein the separation of the magnesium omeprazole is performed by centrifuge or filtration.
28. A process according to claim 2 wherein magnesium omeprazole crystals are washed with water after centrifuge or filtration.
29. A process according to claim 2 wherein the magnesium omeprazole crystals which washed with water are dried at 50-75 °C.
30. A process according to claim 2 wherein the purification of the magnesium omeprazole crystals is performed by washing the crystals with ethyl acetate.
31. A process according to claim 2 wherein the purified magnesium omeprazole crystals which are washed with ethyl acetate are dried at 40-50 °C
32. A process according to claim 2 wherein the water content of purified magnesium omeprazole crystals is 8-12%.
33. A process according to claim 32 wherein the water content of purified magnesium omeprazole crystals is 9-10%.
34. A process according to claim 2 wherein the yield of purified magnesium omeprazole crystals is 90% or more.
35. A process according to claim 2 wherein the manufacture of magnesium salt of omeprazol may be used for the manufacturing the magnesium salt of substituted benzimidazoles such as the compounds with the generic names lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole.
36. A process according to claim 2 wherein the manufacture of calcium salt of omeprazol may be used for the manufacturing the calcium salt of substituted benzimidazoles such as the compounds with the generic names lansoprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole and single enantiomers of omeprazole preferably esomeprazole.
37. A process according to claim 6 wherein calcium hydroxide is used instead of magnesium hydroxide in calcium omeprazole preparation.
38. A process according to claim 7 wherein calcium hydroxide is used instead of magnesium hydroxide in calcium omeprazole preparation.
39. A process according to claims 18, 37 and 38 wherein an alcohol, preferably ethanol is used in calcium omeprazole preparation.
40. A process according to claim 2 wherein magnesium salt of omeprazole active ingredient is used in pharmaceutical formulations such as tablet.
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/TR2004/000014 WO2005082888A1 (en) | 2004-03-01 | 2004-03-01 | Process for the preparation of magnesium salt of omeprazole |
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| PCT/TR2004/000014 WO2005082888A1 (en) | 2004-03-01 | 2004-03-01 | Process for the preparation of magnesium salt of omeprazole |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007041790A1 (en) * | 2005-10-14 | 2007-04-19 | Jon Pty Limited | Salts of proton pump inhibitors and process for preparing same |
| WO2007071753A2 (en) * | 2005-12-23 | 2007-06-28 | Lek Pharmaceuticals D.D. | S-omeprazole magnesium |
| WO2008057559A1 (en) * | 2006-11-06 | 2008-05-15 | Teva Pharmaceutical Industries Ltd. | Processes for preparing substantially pure pantoprazole magnesium |
| WO2009047775A3 (en) * | 2007-10-08 | 2010-02-18 | Hetero Drugs Limited | Polymorphs of esomeprazole salts |
| WO2010097583A1 (en) | 2009-02-24 | 2010-09-02 | Cipla Limited | Esomeprazole potassium polymorph and its preparation |
| WO2011161421A1 (en) * | 2010-06-24 | 2011-12-29 | Cipla Limited | Salts and polymorphs of dexrabeprazole |
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| WO2007041790A1 (en) * | 2005-10-14 | 2007-04-19 | Jon Pty Limited | Salts of proton pump inhibitors and process for preparing same |
| WO2007071753A2 (en) * | 2005-12-23 | 2007-06-28 | Lek Pharmaceuticals D.D. | S-omeprazole magnesium |
| WO2007071753A3 (en) * | 2005-12-23 | 2007-08-02 | Lek Pharmaceuticals | S-omeprazole magnesium |
| WO2008057559A1 (en) * | 2006-11-06 | 2008-05-15 | Teva Pharmaceutical Industries Ltd. | Processes for preparing substantially pure pantoprazole magnesium |
| WO2009047775A3 (en) * | 2007-10-08 | 2010-02-18 | Hetero Drugs Limited | Polymorphs of esomeprazole salts |
| WO2010097583A1 (en) | 2009-02-24 | 2010-09-02 | Cipla Limited | Esomeprazole potassium polymorph and its preparation |
| WO2011161421A1 (en) * | 2010-06-24 | 2011-12-29 | Cipla Limited | Salts and polymorphs of dexrabeprazole |
| US8912337B2 (en) | 2010-06-24 | 2014-12-16 | Cipla Limited | Salts and polymorphs of dexrabeprazole |
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