US20020119194A1 - Pharmaceutical forms for the oral administration of mesna - Google Patents
Pharmaceutical forms for the oral administration of mesna Download PDFInfo
- Publication number
- US20020119194A1 US20020119194A1 US09/982,098 US98209801A US2002119194A1 US 20020119194 A1 US20020119194 A1 US 20020119194A1 US 98209801 A US98209801 A US 98209801A US 2002119194 A1 US2002119194 A1 US 2002119194A1
- Authority
- US
- United States
- Prior art keywords
- mesna
- tablets
- oral administration
- pharmaceutical forms
- granules
- 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.)
- Abandoned
Links
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 title claims abstract description 24
- 229960004635 mesna Drugs 0.000 title claims abstract description 24
- 239000003826 tablet Substances 0.000 claims abstract description 21
- 239000008187 granular material Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000008188 pellet Substances 0.000 claims abstract description 10
- 239000007941 film coated tablet Substances 0.000 claims abstract description 9
- 238000005469 granulation Methods 0.000 claims abstract description 9
- 230000003179 granulation Effects 0.000 claims abstract description 9
- 238000005056 compaction Methods 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000007787 solid Substances 0.000 claims abstract description 6
- 238000007907 direct compression Methods 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- OMDCSPXITNMPHV-UHFFFAOYSA-N 2h-oxaphosphinine Chemical class O1PC=CC=C1 OMDCSPXITNMPHV-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000009481 moist granulation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
Definitions
- Mesna is a known antidote, which is employed for the prophylaxis of the urotoxicity of oxaphosphorines such as ifosphamide and cyclophosphamide.
- oral formulations are also already known.
- Effervescent tablets with 10-80% of mesna are further-more disclosed in U.S. Pat. No. 5,358,718.
- U.S. Pat. No. 5,262,169 describes tablets with 10-80% of mesna.
- the claimed composition is coupled with an alcoholic granulation process.
- EP 0468245 describes mesna tablets which contain 10-80% of mesna, in combination with various auxiliaries. Here too, a process for the production of these tablets by means of granulation in the presence of organic solvents is described. The same problems apply as with the abovementioned US patents.
- the object is thus to produce mesna tablets by means of a simple, economical production method and to do this, if possible, without the use of organic solvents. Since mesna is administered in high doses, it is necessary for the oral mesna formulations to have an active compound content of over 80%.
- the moist mass is granulated and dried at 40° C. on racks.
- the dried granules are mixed with 27.0 g of microcrystalline cellulose and 6.0 g of corn starch. 2.7 g of magnesium stearate are then added and mixing is carried out again.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, produced by granulation with up to 15% of water, based on the amount of solid employed, and also tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, produced by direct compression or compaction. without the use of organic solvents.
Description
- Mesna is a known antidote, which is employed for the prophylaxis of the urotoxicity of oxaphosphorines such as ifosphamide and cyclophosphamide. In addition to parenteral formulations, oral formulations are also already known.
- Thus in U.S. Pat. No. 5,503,845, oral formulations in the form of tablets, pellets, capsules having an active compound content of up to >85% of mesna in combination with a preparation process of moist granulation with more than 30% of water, based on the amount of the solids employed, are described. Problems here are the long and uneconomical drying times to be expected as a result of the large amounts of water. Moreover, high amounts of water also lead to active compound instability.
- Effervescent tablets with 10-80% of mesna are further-more disclosed in U.S. Pat. No. 5,358,718. U.S. Pat. No. 5,262,169 describes tablets with 10-80% of mesna. In both abovementioned patent specifications, the claimed composition is coupled with an alcoholic granulation process.
- The use of organic liquids in granulation, however, is to be classified as problematical, since these substances are usually environmentally harmful, and moreover special arrangements are needed for employee protection.
- EP 0468245 describes mesna tablets which contain 10-80% of mesna, in combination with various auxiliaries. Here too, a process for the production of these tablets by means of granulation in the presence of organic solvents is described. The same problems apply as with the abovementioned US patents.
- The object is thus to produce mesna tablets by means of a simple, economical production method and to do this, if possible, without the use of organic solvents. Since mesna is administered in high doses, it is necessary for the oral mesna formulations to have an active compound content of over 80%.
- Surprisingly, it was possible to achieve the object mentioned by producing pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, by granulation with up to 15% of water, based on the amount of solid employed, or pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna by direct compression or compaction. It is to be emphasized that the process for the production of pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules by granulation, direct compression or compaction manages without the use of organic solvents.
- The invention is illustrated in greater detail by means of the following working examples without, however, being restricted thereby.
- Tablets with 100% of Mesna
- 500 g of mesna are sieved and moistened with 97 g of water (=19.4% based on the solid). The mixture is then granulated, and dried at 40° C. on racks. The granules are compressed to give tablets.
Weight: 500 mg Breaking strength: 70-80 N Disintegration: <1.5 min. - Tablets with 88% of mesna
- Pure aqueous granulation with 5.6% of water
- 2.7 g of corn starch are dissolved in 3.3 g of water and swollen in 13.7 g of water.
- 300 g of mesna are sieved and kneaded together with swollen corn starch.
- The moist mass is granulated and dried at 40° C. on racks. The dried granules are mixed with 27.0 g of microcrystalline cellulose and 6.0 g of corn starch. 2.7 g of magnesium stearate are then added and mixing is carried out again.
Weight: 225.6 mg Breaking strength: 100 N Disintegration: <4 min. - Tablets with 81.6% of mesna Compaction.
- 200 g of mesna are sieved together with 30.0 g of lactose and 10.0 g of highly disperse silica and mixed. 5.0 g of magnesium stearate are then added and mixing is carried out again. The mass prepared in this way is compressed to give pressed tablets. The pressed tablets are comminuted and sieved. The material resulting in this way is mixed and processed to give tablets.
Weight: 245 mg Breaking strength: 50 N Disintegration: <3 min.
Claims (4)
1. Pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, produced by granulation with up to 15% of water, based on the amount of solid employed.
2. Pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, produced by direct compression or compaction.
3. Process for the production of pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 88% of mesna, according to claim 1 , by granulation with up to 15% of water, based on the amount of solid employed, without the use of organic solvents.
4. Process for the production of pharmaceutical forms for oral administration in the form of tablets, film-coated tablets, pellets or granules comprising at least 80% of mesna, according to claim 2 , by direct compression or compaction without the use of organic solvents.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/982,098 US20020119194A1 (en) | 1998-04-27 | 2001-10-19 | Pharmaceutical forms for the oral administration of mesna |
| US10/336,006 US20030119906A1 (en) | 1998-04-27 | 2003-01-03 | Pharmaceutical forms for the oral administration of mesna |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19818804.8 | 1998-04-27 | ||
| DE19818804 | 1998-04-27 | ||
| US09/300,291 US6322812B1 (en) | 1998-04-27 | 1999-04-27 | Pharmaceutical forms for the oral administration of mesna |
| US09/982,098 US20020119194A1 (en) | 1998-04-27 | 2001-10-19 | Pharmaceutical forms for the oral administration of mesna |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/300,291 Continuation US6322812B1 (en) | 1998-04-27 | 1999-04-27 | Pharmaceutical forms for the oral administration of mesna |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/336,006 Continuation US20030119906A1 (en) | 1998-04-27 | 2003-01-03 | Pharmaceutical forms for the oral administration of mesna |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20020119194A1 true US20020119194A1 (en) | 2002-08-29 |
Family
ID=7865949
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/300,291 Expired - Lifetime US6322812B1 (en) | 1998-04-27 | 1999-04-27 | Pharmaceutical forms for the oral administration of mesna |
| US09/982,098 Abandoned US20020119194A1 (en) | 1998-04-27 | 2001-10-19 | Pharmaceutical forms for the oral administration of mesna |
| US10/336,006 Abandoned US20030119906A1 (en) | 1998-04-27 | 2003-01-03 | Pharmaceutical forms for the oral administration of mesna |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/300,291 Expired - Lifetime US6322812B1 (en) | 1998-04-27 | 1999-04-27 | Pharmaceutical forms for the oral administration of mesna |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/336,006 Abandoned US20030119906A1 (en) | 1998-04-27 | 2003-01-03 | Pharmaceutical forms for the oral administration of mesna |
Country Status (3)
| Country | Link |
|---|---|
| US (3) | US6322812B1 (en) |
| EP (1) | EP0955040A1 (en) |
| CA (1) | CA2269888A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0955040A1 (en) * | 1998-04-27 | 1999-11-10 | ASTA Medica Aktiengesellschaft | Oral composition comprising mesna |
| US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
| CA2765033C (en) | 2009-06-12 | 2020-07-14 | Meritage Pharma, Inc. | Methods for treating gastrointestinal disorders |
| WO2016159684A1 (en) * | 2015-04-01 | 2016-10-06 | 주식회사 아모레퍼시픽 | Composition for promoting skin regeneration containing sodium 2-mercaptoethane sulfonate |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0468245T3 (en) * | 1990-07-16 | 1994-05-16 | Asta Medica Ag | Tablet and granules containing mesna as active agent |
| US5252341A (en) | 1990-07-16 | 1993-10-12 | Degussa Aktiengesellschaft | Tablets and granulates containing mesna as active substance |
| DE9321574U1 (en) * | 1992-03-11 | 2000-06-29 | Asta Medica Ag, 01277 Dresden | Tablets, granules and pellets with a high content of active ingredients for highly concentrated, solid dosage forms |
| EP0955040A1 (en) * | 1998-04-27 | 1999-11-10 | ASTA Medica Aktiengesellschaft | Oral composition comprising mesna |
-
1999
- 1999-04-12 EP EP99107080A patent/EP0955040A1/en not_active Withdrawn
- 1999-04-26 CA CA002269888A patent/CA2269888A1/en not_active Abandoned
- 1999-04-27 US US09/300,291 patent/US6322812B1/en not_active Expired - Lifetime
-
2001
- 2001-10-19 US US09/982,098 patent/US20020119194A1/en not_active Abandoned
-
2003
- 2003-01-03 US US10/336,006 patent/US20030119906A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20030119906A1 (en) | 2003-06-26 |
| US6322812B1 (en) | 2001-11-27 |
| CA2269888A1 (en) | 1999-10-27 |
| EP0955040A1 (en) | 1999-11-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: ASTA MEDICA AG, GERMANY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:RAWERT, JURGEN;SARLIKIOTIS, WERNER;REEL/FRAME:012608/0310;SIGNING DATES FROM 20020118 TO 20020122 |
|
| STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |