AU2002216042A1 - Freeze-dried pantoprazole preparation and pantoprazole injection - Google Patents
Freeze-dried pantoprazole preparation and pantoprazole injectionInfo
- Publication number
- AU2002216042A1 AU2002216042A1 AU2002216042A AU2002216042A AU2002216042A1 AU 2002216042 A1 AU2002216042 A1 AU 2002216042A1 AU 2002216042 A AU2002216042 A AU 2002216042A AU 2002216042 A AU2002216042 A AU 2002216042A AU 2002216042 A1 AU2002216042 A1 AU 2002216042A1
- Authority
- AU
- Australia
- Prior art keywords
- pantoprazole
- salt
- injection
- freeze
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 title claims description 45
- 229960005019 pantoprazole Drugs 0.000 title claims description 40
- 229940026447 pantoprazole injection Drugs 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000000243 solution Substances 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000002347 injection Methods 0.000 claims description 16
- 239000007924 injection Substances 0.000 claims description 16
- 239000002245 particle Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 10
- 229940090044 injection Drugs 0.000 claims description 9
- 238000004108 freeze drying Methods 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000012906 subvisible particle Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000012538 light obscuration Methods 0.000 claims description 4
- 239000002504 physiological saline solution Substances 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims 1
- 238000001035 drying Methods 0.000 description 12
- 239000008215 water for injection Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 239000011521 glass Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 3
- 229960004048 pantoprazole sodium Drugs 0.000 description 3
- YNWDKZIIWCEDEE-UHFFFAOYSA-N pantoprazole sodium Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC YNWDKZIIWCEDEE-UHFFFAOYSA-N 0.000 description 3
- 239000013618 particulate matter Substances 0.000 description 3
- -1 2-[(2-pyridyl)methylsulfinyl]-benzimidazole compound Chemical class 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- PWWDEIMGEBPTJL-UHFFFAOYSA-N 1-(pyridin-2-ylmethylsulfinyl)benzimidazole Chemical class C1=NC2=CC=CC=C2N1S(=O)CC1=CC=CC=N1 PWWDEIMGEBPTJL-UHFFFAOYSA-N 0.000 description 1
- IQPSEEYGBUAQFF-SANMLTNESA-N 6-(difluoromethoxy)-2-[(s)-(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(C[S@](=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-SANMLTNESA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- YXLFRKFUVHZXID-UHFFFAOYSA-G [Na+].[Na+].[Na+].C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C(CN)N.[Na+].[Na+].[Ca+2].C(C)(=O)[O-].C(C)(=O)O.C(C)(=O)[O-].C(C)(=O)[O-].C(CN)N Chemical compound [Na+].[Na+].[Na+].C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C(C)(=O)[O-].C(CN)N.[Na+].[Na+].[Ca+2].C(C)(=O)[O-].C(C)(=O)O.C(C)(=O)[O-].C(C)(=O)[O-].C(CN)N YXLFRKFUVHZXID-UHFFFAOYSA-G 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- RDRUTBCDIVCMMX-UHFFFAOYSA-N magnesium;5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Mg+2].COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC.COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC RDRUTBCDIVCMMX-UHFFFAOYSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- FEJQDYXPAQVBCA-UHFFFAOYSA-J tetrasodium;ethane-1,2-diamine;tetraacetate Chemical compound [Na+].[Na+].[Na+].[Na+].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.NCCN FEJQDYXPAQVBCA-UHFFFAOYSA-J 0.000 description 1
- 239000012905 visible particle Substances 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
Description
Freeze-dried Pantoprazole Preparation and Pantoprazole Injection
Technical Field
The present invention relates to the field of pharmaceutical technology and describes freeze-dried 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)methylsulfinyl]-1 H-benzimidazole preparations and a 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)methylsulfinyl]-1 H-benzimidazole injection. Furthermore the invention also relates to a process for the production of freeze-dried 5-difluoromethoxy- 2-[(3,4-dimethoxy-2-pyridinyl)methylsulfinyl]-1 H-benzimidazole and a 5-difluoromethoxy-2-[(3,4-dirneth- oxy-2-pyridinyl)methylsulfinyl]-1 H-benzimidazole injection.
Prior art
WO94/02141 describes an injection comprising a 2-[(2-pyridyl)methylsulfinyl]-benzimidazole compound an aqueous solvent added with no nonaqueous solvent, wherein the pH of the injection is not less than 9.5 and not more than 11.5. It is mentioned that said injection does not cause hemolysis and causes less local irritation.
DE 43 24 014 describes the preparation of a lyophilisate of pantoprazole-sodium sesquihydrate in the presence of sucrose as an auxiliary at production temperatures of -25 to -30°C. It is disclosed that the lyophilisate is of improved storage stability and can be stored at room temperature for at least 18 months and is easily reconstituted in liquid form in suitable doses for use.
CN 1235018 describes a freeze-dried injection powder of pantoprazole sodium containing no crystallised water with pH value of 9-12.5, which is composed of pantoprazole sodium, freeze-dried powder supporting agent, metal ion complexing agent and pH regulator.
W099/18959 describes aqueous pharmaceutical compositions which are chemically and physically stable for intravenous injection which comprise anti-ulcerative compound and glycine as stabilizer in carrier.
Description of invention
Reconstitution of lyophilised pharmaceutical compounds with carrier solutions for application may lead to the formation of visible and/or subvisible particles in the solution. Injectable solutions, including solutions constituted from sterile solids intended for parenteral use should be essentially free from particles that can be observed on visual inspection and for patient safety it is also desirable to have a low number of subvisible particles. USP (United States Pharmacopeia) 24 describes physical tests performed for the purpose of enumerating subvisible extraneous particles within specific size ranges and also defines particulate matters limits set forth for the test being applied for large-volume injections for single-dose infusion and small-volume injections (USP 24, <788> Particulate Matter in Injections).
Surprisingly it has now been found that by freeze drying of an aqueous solution of pantoprazole, ethylenediamine tetraacetic acid and/or a suitable salt thereof, and sodium hydroxide and/or sodium carbonate a lyophilisate is obtained having significantly lower number of subvisible particles after reconsti- tuion with a solvent compared to lyophilisates of the state of the art. The lyophilisate according to the invention is very stabile and is easily reconstituted with suitable solvents. In particular the pantoprazole injection according to the invention has less than 130, preferably less than 120 subvisible particles/per vial, the particles having a size equal to or greater as 10μm, the number of particles determined according to USP 24 (<788> Particle Matter in Injections) by light obscuration particle test count.
5-Difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)methylsulfinyI]-1 H-benzimidazole (INN: pantoprazole, in connection with the invention also referred to as pantoprazole) is known from EP-A-0 166 287. Pantoprazole is a chiral compound. In connection with the invention the term pantoprazole also includes the pure enantiomers of pantoprazole and their mixtures in any mixing ratio. (S)-pantoprazoIe [(-)-pantoprazole] may be mentioned by way of example. Pantoprazole is present here as such or preferably in the form of it's salt with a base. Examples of salts with a base which may be mentioned are sodium, potassium, magnesium and calcium salts. Pantoprazole and/or a salt thereof may contain, various amounts of solvent when isolated in crystalline form. In connection with the invention pantoprazole also refers to all solvates and in particular to hydrates of 5-difluoromethoxy-2-[(3,4-dimethoxy-2- pyridinyl)methylsulfinyl]-1 H-benzimidazole and salts thereof. Such a hydrate of the salt of pantoprazole with a base is disclosed, for example, in WO91/19710. Expediently pantoprazole refers to pantoprazole sodium sesquihydrate (= pantoprazole sodium x 1.5 H20) and pantoprazole magnesium dihydrate.
According to the invention the pantoprazole solution used in the freeze drying process can be obtained by addition of ethylenediamine tetraacetic acid and/or a suitable salt thereof, and sodium hydroxide and/or sodium carbonate to an aqueous solvent. Suitable salts of ethylenediamine tetraacetic acid which may be mentioned in connection with the invention by way of example are ethylenediamine
tetraacetic acid disodium salt, ethylenediamine tetraacetic acid calcium disodium salt ethylenediamine tetraacetic acid trisodium salt and ethylenediamine tetraacetic acid tetrasodium salt. The proportion by weight of ethylenediamine tetraacetic acid and/or a suitable salt thereof, based on the amount of pantoprazole used is from 0.05 to 25 % preferably from 0.25 to 12.5 % or particular preferred from 1 to 5 %. The aqueous solvent preferentially is water for injection. Subsequently pantoprazole is added to the solution and dissolved by stirring. It is preferred to have a solution wherein the proportion of weight (m/m) of pantoprazole is 0.5 to 10 %, particularly preferred 1 to 6 %. In a further preferred embodiment of the invention the pH of the solution used in the freeze drying process is 8 or above 8, particularly preferred the pH is in the range from 10 to 13. Then this solution is filtered for sterilization and charged in vials. The solution is then freeze dried by a method known per se.
A pantoprazole injection according to the invention can be produced by dissolving the lyophilized product thus obtained in a suitable solvent for example physiological saline, aqueous solution of 5% glucose, or distilled water for injection. Preferably the pantoprazole injection according to the invention is used in the form of intravenous injection.
The lyophilised product and pantoprazole injection according to the invention preferably contain pantoprazole in the dose customary for the treatment of the respective disease. The lyophilised product and pantoprazole injection according to the invention can be employed for the treatment and prevention of all the diseases which are regarded as treatable or avoidable by the use of pyridin-2-ylmethylsulfinyl- 1 H-benzimidazoles. In particular, the lyophilised product and pantoprazole injection according to the invention can be employed in the treatment of stomach disorders. The lyophilized products in particular contain between 5 and 150 mg, preferably between 5 and 60 mg, of pantoprazole. Examples which may be mentioned are lyophilized products or injections which contain 10, 20, 40, 50 or 96 mg of pantoprazole. The administration of the daily dose (e.g. 40 mg of active compound) can be carried out, for example, in the form of an individual dose or by means of a number of doses of the administration forms according to the invention (e.g. 2 times 20 mg of active compound). The concentration of pantoprazole in the injection according to the invention may vary depending upon the administration route and generally ranges in a proportion of 0.05-10 mg/ml, preferably 0.1 to 5 mg/ml on a free compound basis. For example for bolus administration 20 to 120 mg of lyophilized product according to the invention can be reconstituted with 10 ml physiological saline.
The production of the lyophilized product and pantoprazole injection is described by way of example below. The following examples illustrate the invention in greater detail, without restricting it.
Examples
Production of a lyophilized pantoprazole preparation
Example 1
Under nitrogen atmosphere, 0.276 g Ethylenediamine tetraacetic acid disodium salt and 6.7 g sodium hydroxide (1 aqueous solution) are added to 480 g water for injection of 4°C to 8°C. 12.47 g pantoprazole sodium sesquihydrate is added while stirring to give a clear solution. The weight of the solution is adjusted to 500 g by addition of water for injection. The pH of the solution is 11.76. The solution is filtered through a 0.2 μm membrane filter and filled in glass vials (1.81 g by vial). Filled vials are semi- stoppered and put into a freeze-dryer (GT4 Edwards/Kniese or GT8 Amsco) for lyophilisation. The vials are cooled to -45°C, then the temperature is raised to -20 to -5°C under vacuum (0.1 to 0.5 mbar) for drying. After finishing main drying the temperature is raised to 30°C, the vacuum is adjusted to 0.01 mbar and drying is continued for an additional 3 hours. An off-white lyophilized product is obtained which is easily reconstituted with physiological saline to give a clear solution.
Comparative Examples
Example 2
Under nitrogen atmosphere, 12.47 g pantoprazole sodium sesquihydrate is added to 480 g water for injection of 4°C to 8°C while stirring to give a clear solution. The volume of the solution is adjusted to 500 g by addition of water for injection. The pH of the solution is 10.85. The solution is filtered through a 0.2 μm membrane filter and filled in glass vials (1.81 g by vial). Filled vials are semi-stoppered and put into a freeze-dryer (GT4 Edwards/Kniese or GT8 Amsco) for lyophilisation. The vials are cooled to -45°C, then the temperature is raised to -20 to -5°C under vacuum (0.1 to 0.5 mbar) for drying. After finishing main drying the temperature is raised to 30°C, the vacuum is adjusted to 0.01 mbar and drying is continued for an additional 3 hours. An off-white lyophilized product is obtained.
Example 3
Under nitrogen atmosphere, 2.45 g sodium hydroxide (1 N aqueous solution) is added to 480 g water for injection of 4°C to 8°C. 12.47 g pantoprazole sodium sesquihydrate is added while stirring to give a clear solution. The weight of the solution is adjusted to 500 g by addition of water for injection. The pH of the solution is 12.02. The solution is filtered through a 0.2 μm membrane filter and filled in glass vials (1.81 g by vial). Filled vials are semi-stoppered and put into a freeze-dryer (GT4 Edwards/Kniese or GT8 Amsco) for lyophilisation. The vials are cooled to -45°C, then the temperature is raised to -20 to -
5°C under vacuum (0.1 to 0.5 mbar) for drying. After finishing main drying the temperature is raised to 30°C, the vacuum is adjusted to 0.01 mbar and drying is continued for an additional 3 hours. An off- white lyophilized product is obtained.
Example 4
Under nitrogen atmosphere, 0.05 g Ethylenediamine tetraacetic acid disodium salt is added to 480 g water for injection of 4°C to 8°C. 12.47 g pantoprazole sodium sesquihydrate is added while stirring to give a clear solution. The weight of the solution is adjusted to 500 g by addition of water for injection. The pH of the solution is 10.2. The solution is filtered through a 0.2 μm membrane filter and filled in glass vials (1.81 g by vial). Filled vials are semi-stoppered and put into a freeze-dryer (GT4 Edwards/- Kniese or GT8 Amsco) for lyophilisation. The vials are cooled to -45°C, then the temperature is raised to -20 to -5°C under vacuum (0.1 to 0.5 mbar) for drying. After finishing main drying the temperature is raised to 30°C, the vacuum is adjusted to 0.01 mbar and drying is continued for an additional 3 hours. An off-white lyophilized product is obtained.
Light obscuration particle test count
Particulate matter/per vial in solutions constituted from the lyophilized products obtained according to Examples 1 to 4 were determined according to USP 24 (<788> Particulate Matter in Injections) by light obscuration particle test count.
The number of extraneous particles per vial having a size equal to or greater as 10 μm detected are summarized in Table 1. As may be evident from table 1 , the number of subvisible particles per vial (equal to or greater as 10μm) in solutions constituted from products obtained according to the invention (EXAMPLE 1 ) is lower than for products obtained by methods which differ from the present invention (EXAMPLES 2 to 4).
Table 1:
Claims (10)
1. Process for the production of a freeze-dried preparation comprising 5-difluoromethoxy-2-[(3,4-di- methoxy-2-pyridinyl)methylsulfinyl]-1 H-benzimidazole (pantoprazole), a salt thereof, a solvate of pantoprazole or a salt thereof, comprising freeze-drying of an aqueous solution of pantoprazole, a salt thereof, a solvate of pantoprazole or a salt thereof, ethylenediamine tetraacetic acid and/or a suitable salt thereof, and sodium hydroxide and/or sodium carbonate.
2. Process according to claim 1, comprising dissolution of ethylenediamine tetraacetic acid and/or a suitable salt thereof in water, adjusting pH of the solution to 8 or above 8 by addition of sodium hydroxide and/or sodium carbonate and addition of pantoprazole, a salt thereof, a solvate of pantoprazole or a salt thereof, to the thus obtained solution.
3. Process according to claim 1 , wherein the proportion by weight of ethylenediamine tetraacetic acid and/or a suitable salt thereof, based on the amount of pantoprazole present is from 0.05 to 25 %, from 0.25 to 12.5 %, or from 1 to 5 %.
4. Process according to claim 1 , wherein pantoprazole is pantoprazole sodium sesquihydrate.
5. Process according to claim 1 wherein the pH of the aqueous solution is in the range from 10 to 13.
6. Lyophilized pantoprazole preparation obtainable by a process according to claims 1 to 5.
7. Pantoprazole injection for bolus administration obtainable by reconstitution of the pantoprazole preparation according to claim 6 in a suitable solvent.
8. Pantoprazole injection according to claim 7, wherein the solvent is physiological saline.
9. Injection kit comprising a lyophilized pantoprazole preparation according to claim 6 and a solvent suitable for bolus administration.
10. Pantoprazole injection having less than 130, preferably less than 120 subvisible particles/per vial, the particles having a size equal to or greater as 10 μm, the number of particles determined according to USP 24 (<788> Particle Matter in Injections) by light obscuration particle test count.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2006235847A AU2006235847C1 (en) | 2000-11-22 | 2006-11-03 | Lyophilized pantoprazole preparation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00125569 | 2000-11-22 | ||
| EP00125569.4 | 2000-11-22 | ||
| PCT/EP2001/013296 WO2002041919A1 (en) | 2000-11-22 | 2001-11-17 | Freeze-dried pantoprazole preparation and pantoprazole injection |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2006235847A Division AU2006235847C1 (en) | 2000-11-22 | 2006-11-03 | Lyophilized pantoprazole preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002216042A1 true AU2002216042A1 (en) | 2002-08-08 |
| AU2002216042B2 AU2002216042B2 (en) | 2006-08-03 |
Family
ID=8170452
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU1604202A Pending AU1604202A (en) | 2000-11-22 | 2001-11-17 | Freeze-dried pantoprazole preparation and pantoprazole injection |
| AU2002216042A Expired AU2002216042B2 (en) | 2000-11-22 | 2001-11-17 | Freeze-dried pantoprazole preparation and pantoprazole injection |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU1604202A Pending AU1604202A (en) | 2000-11-22 | 2001-11-17 | Freeze-dried pantoprazole preparation and pantoprazole injection |
Country Status (39)
| Country | Link |
|---|---|
| US (3) | US6780881B2 (en) |
| EP (2) | EP1762249A3 (en) |
| JP (1) | JP4886158B2 (en) |
| KR (2) | KR100910607B1 (en) |
| CN (1) | CN1250292C (en) |
| AR (2) | AR034277A1 (en) |
| AT (1) | ATE381946T1 (en) |
| AU (2) | AU1604202A (en) |
| BG (1) | BG66329B1 (en) |
| BR (1) | BRPI0115483B8 (en) |
| CA (2) | CA2541946A1 (en) |
| CY (1) | CY1107896T1 (en) |
| CZ (1) | CZ304348B6 (en) |
| DE (1) | DE60132108T2 (en) |
| DK (1) | DK1339430T3 (en) |
| EA (1) | EA007602B1 (en) |
| EC (1) | ECSP034613A (en) |
| EE (1) | EE05236B1 (en) |
| ES (1) | ES2298295T3 (en) |
| GE (1) | GEP20053461B (en) |
| HR (1) | HRP20030410B1 (en) |
| HU (1) | HUP0303278A3 (en) |
| IL (2) | IL155601A0 (en) |
| IS (1) | IS2971B (en) |
| ME (1) | ME00556B (en) |
| MX (1) | MXPA03004548A (en) |
| MY (1) | MY137726A (en) |
| NO (1) | NO332937B1 (en) |
| NZ (1) | NZ525911A (en) |
| PE (1) | PE20020582A1 (en) |
| PL (1) | PL201188B1 (en) |
| PT (1) | PT1339430E (en) |
| RS (1) | RS52024B (en) |
| SI (1) | SI1339430T1 (en) |
| SK (1) | SK287993B6 (en) |
| TW (1) | TWI284041B (en) |
| UA (1) | UA80961C2 (en) |
| WO (1) | WO2002041919A1 (en) |
| ZA (1) | ZA200303593B (en) |
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