CA2239931A1 - Pharmaceutical tablet comprising norfloxacin - Google Patents
Pharmaceutical tablet comprising norfloxacin Download PDFInfo
- Publication number
- CA2239931A1 CA2239931A1 CA 2239931 CA2239931A CA2239931A1 CA 2239931 A1 CA2239931 A1 CA 2239931A1 CA 2239931 CA2239931 CA 2239931 CA 2239931 A CA2239931 A CA 2239931A CA 2239931 A1 CA2239931 A1 CA 2239931A1
- Authority
- CA
- Canada
- Prior art keywords
- norfloxacin
- tablets
- tablet
- dissolution
- disintegrant
- 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
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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
Abstract
A direct compression tablet formulation comprising norfloxacin and a disintegrant selected from crospovidone and sodium starch glycolate.
Description
PHARMACEUTICAL TABLET COMPRISING NORFLOXACIN
BACKGROUND OF THE INVENTION
Norfloxacin is a quinoline carboxylic acid known to be effective as an antibacterial agent when administered orally.
Its formulation into a tablet oral dosage form is disclosed in Italian patent application No. 20764A/79. This formulation requires that it contains about 2% to about 15% water to permit preparation of a tablet containing the minimal amount of inert ingredients (carriers, etc.) and having suitable dissolution, disintegration and bioavailability characteristics. The water is added to the formulation ingredients prior to compression into tablets.
It is highly desirable to use a formulation method whereby the ingredients can be mixed and processed into tablets completely in dry form, so as to avoid the need to add water or other solvents. Such tablets made without use of water or another solvent are known as direct compression tablets.
U.S. patent 4639458 discloses a tablet formulation for norfloxacin which does not require use of water or any other solvent and which still enables satisfactory disintegration, dissolution and bioavailability properties.
The tablets of U.S. patent 4639458 are made by mixing in dry form norfloxacin, microcrystalline cellulose, croscarmellose sodium and magnesium stearate, and compressing the powder mixture into tablets. In this formulation, the microcrystalline cellulose serves as a binder to enable formation of a hard tablet upon compression, the croscarmellose sodium is a disintegrant to cause disintegration of the tablet in gastrointestinal fluid after ingestion, and the magnesium stearate is a lubricant to prevent sticking of the tablet to the punches used in the tabletting process.
While the invention of U.S. patent 4639458 enables tablets that are said to be satisfactory, the present inventor has found that use of croscarmellose sodium as disintegrant in direct compression norfloxacin tablets does not necessarily enable complete dissolution when tested by the method specified in the United States Pharmacopoeia Edition 23 (USP23).
More specifically, the USP23 provides that the dissolution test procedure is performed in 750 mL of phosphate buffer pH4.0, using apparatus No. 2, with a paddle speed of 50 rpm, and the specification requires dissolution of at least 80% in 30 minutes.
It has been found that direct compression norfloxacin tablets using croscarmellose sodium as disintegrant do not disintegrate into fine particles but only into relatively large granules with the result that, in the dissolution test, the dissolution goes only to about 90% in 30 minutes. While such tablets still meet the USP23 specification, it is desirable to have tablets which give dissolution of 100% and not just 90%.
These results differ from those disclosed in U.S. patent 4639458, which indicates complete dissolution at 10, 20 and 30 minutes. It thus appears that the dissolution rate achieved may be dependent on some physical property of the norfloxacin that is used.
In view of this problem with prior art norfloxacin tablets, it is the object of the present invention to enable direct compression norfloxacin tablets which consistently provide essentially complete dissolution in 30 minutes.
BACKGROUND OF THE INVENTION
Norfloxacin is a quinoline carboxylic acid known to be effective as an antibacterial agent when administered orally.
Its formulation into a tablet oral dosage form is disclosed in Italian patent application No. 20764A/79. This formulation requires that it contains about 2% to about 15% water to permit preparation of a tablet containing the minimal amount of inert ingredients (carriers, etc.) and having suitable dissolution, disintegration and bioavailability characteristics. The water is added to the formulation ingredients prior to compression into tablets.
It is highly desirable to use a formulation method whereby the ingredients can be mixed and processed into tablets completely in dry form, so as to avoid the need to add water or other solvents. Such tablets made without use of water or another solvent are known as direct compression tablets.
U.S. patent 4639458 discloses a tablet formulation for norfloxacin which does not require use of water or any other solvent and which still enables satisfactory disintegration, dissolution and bioavailability properties.
The tablets of U.S. patent 4639458 are made by mixing in dry form norfloxacin, microcrystalline cellulose, croscarmellose sodium and magnesium stearate, and compressing the powder mixture into tablets. In this formulation, the microcrystalline cellulose serves as a binder to enable formation of a hard tablet upon compression, the croscarmellose sodium is a disintegrant to cause disintegration of the tablet in gastrointestinal fluid after ingestion, and the magnesium stearate is a lubricant to prevent sticking of the tablet to the punches used in the tabletting process.
While the invention of U.S. patent 4639458 enables tablets that are said to be satisfactory, the present inventor has found that use of croscarmellose sodium as disintegrant in direct compression norfloxacin tablets does not necessarily enable complete dissolution when tested by the method specified in the United States Pharmacopoeia Edition 23 (USP23).
More specifically, the USP23 provides that the dissolution test procedure is performed in 750 mL of phosphate buffer pH4.0, using apparatus No. 2, with a paddle speed of 50 rpm, and the specification requires dissolution of at least 80% in 30 minutes.
It has been found that direct compression norfloxacin tablets using croscarmellose sodium as disintegrant do not disintegrate into fine particles but only into relatively large granules with the result that, in the dissolution test, the dissolution goes only to about 90% in 30 minutes. While such tablets still meet the USP23 specification, it is desirable to have tablets which give dissolution of 100% and not just 90%.
These results differ from those disclosed in U.S. patent 4639458, which indicates complete dissolution at 10, 20 and 30 minutes. It thus appears that the dissolution rate achieved may be dependent on some physical property of the norfloxacin that is used.
In view of this problem with prior art norfloxacin tablets, it is the object of the present invention to enable direct compression norfloxacin tablets which consistently provide essentially complete dissolution in 30 minutes.
BRIEF SUMMARY OF THE INVENTION
It has surprisingly been found that the use of crospovidone or sodium starch glycolate as disintegrant in place of croscarmellose sodium enables direct compression norfloxacin tablets with superior disintegration and dissolution characteristics.
DETAILED DESCRIPTION OF THE INVENTION
There are numerous substances used as disintegrants in pharmaceutical tablets. One of the most common is croscarmellose sodium, which is generally believed to be a preferred choice of disintegrant because of its high efficiency as a disintegrant and its relatively low cost. Among other known disintegrants are crospovidone and sodium starch glycolate, which are used less frequently because of the fact that they are usually found to be less effective than croscarmellose sodium as a disintegrant. Also, crosprovidone is more expensive than croscarmellose sodium.
It has been surprisingly found that, in the case of direct compression norfloxacin tablets, crospovidone and sodium starch glycolate are with superior disintegrants in that they provide disintegration into finer particles and enable achievement of more rapid and more complete dissolution.
Accordingly, the present invention provides for direct compression norfloxacin tablets which comprise norfloxacin as the active ingredient and either crospovidone or sodium starch glycolate as disintegrant. The norfloxacin tablets will preferably comprise from about 70% to about 95% of the tablet weight and the crospovidone or sodium starch glycolate from about 2% to about 30% of the tablet weight. The tablets will preferably further comprise a lubricant which will usually be present at a level of about 0.5% to 3% of tablet weight. The lubricant will preferably be a stearate, such as magnesium stearate.
It has surprisingly been found that the use of crospovidone or sodium starch glycolate as disintegrant in place of croscarmellose sodium enables direct compression norfloxacin tablets with superior disintegration and dissolution characteristics.
DETAILED DESCRIPTION OF THE INVENTION
There are numerous substances used as disintegrants in pharmaceutical tablets. One of the most common is croscarmellose sodium, which is generally believed to be a preferred choice of disintegrant because of its high efficiency as a disintegrant and its relatively low cost. Among other known disintegrants are crospovidone and sodium starch glycolate, which are used less frequently because of the fact that they are usually found to be less effective than croscarmellose sodium as a disintegrant. Also, crosprovidone is more expensive than croscarmellose sodium.
It has been surprisingly found that, in the case of direct compression norfloxacin tablets, crospovidone and sodium starch glycolate are with superior disintegrants in that they provide disintegration into finer particles and enable achievement of more rapid and more complete dissolution.
Accordingly, the present invention provides for direct compression norfloxacin tablets which comprise norfloxacin as the active ingredient and either crospovidone or sodium starch glycolate as disintegrant. The norfloxacin tablets will preferably comprise from about 70% to about 95% of the tablet weight and the crospovidone or sodium starch glycolate from about 2% to about 30% of the tablet weight. The tablets will preferably further comprise a lubricant which will usually be present at a level of about 0.5% to 3% of tablet weight. The lubricant will preferably be a stearate, such as magnesium stearate.
The tablets will optionally include other ingredients such as, for example, microcrystalline cellulose as a binder to improve tablet hardness, colouring agents, and colloidal silicon dioxide as glidant. The tablets will optionally be film-coated.
The quantity of norfloxacin per tablet will preferably be about 400 mg.
Direct compression norfloxacin tablets containing 400 mg norfloxacin per tablet were made using formulation A and B as follows Component A B C
Norfloxacin 400 mg 400 mg 400 mg Croscarmellose Sodium 88 mg 0 mg 0 mg Crospovidone 0 mg 88 mg 0 mg Sodium Starch Glycolate 0 mg 0 mg 88 mg Magnesium Stearate 11.4 mg 11.4 mg 11.4 mg Colloidal Silicon Dioxide 0.6 mg 0.6 mg 0.6 mg TOTAL 500 mg 500 mg 500 mg _______ _______ _______ In each case, the ingredients were mixed together, the mixed powder was compressed into slugs, the slugs were ground up into free flowing granules, and the granules were compressed into tablets of weight 500 mg each.
Tablets of formulations A, B and C were tested for dissolution following the method specified in USP23.
In the dissolution test, it was observed that tablets A disintegrated into relatively large pieces, where tablets B and C disintegrated into fine particles.
After 30 minutes, the extent of dissolution of tablets B and C was complete, where that of tablets A was only about 90%.
It is thus seen that the use of crospovidone or sodium starch glycolate in place of croscarmellose sodium in direct compression norfloxacin tablets surprisingly provides superior disintegration and dissolution characteristics.
The quantity of norfloxacin per tablet will preferably be about 400 mg.
Direct compression norfloxacin tablets containing 400 mg norfloxacin per tablet were made using formulation A and B as follows Component A B C
Norfloxacin 400 mg 400 mg 400 mg Croscarmellose Sodium 88 mg 0 mg 0 mg Crospovidone 0 mg 88 mg 0 mg Sodium Starch Glycolate 0 mg 0 mg 88 mg Magnesium Stearate 11.4 mg 11.4 mg 11.4 mg Colloidal Silicon Dioxide 0.6 mg 0.6 mg 0.6 mg TOTAL 500 mg 500 mg 500 mg _______ _______ _______ In each case, the ingredients were mixed together, the mixed powder was compressed into slugs, the slugs were ground up into free flowing granules, and the granules were compressed into tablets of weight 500 mg each.
Tablets of formulations A, B and C were tested for dissolution following the method specified in USP23.
In the dissolution test, it was observed that tablets A disintegrated into relatively large pieces, where tablets B and C disintegrated into fine particles.
After 30 minutes, the extent of dissolution of tablets B and C was complete, where that of tablets A was only about 90%.
It is thus seen that the use of crospovidone or sodium starch glycolate in place of croscarmellose sodium in direct compression norfloxacin tablets surprisingly provides superior disintegration and dissolution characteristics.
Claims (8)
1. A pharmaceutical tablet comprising norfloxacin and a disintegrant selected from crospovidone and sodium starch glycolate.
2. A tablet as in Claim 1 wherein the disintegrant is crospovidone.
3. A tablet as in Claim 1 wherein the disintegrant is sodium starch glycolate.
4. A tablet as in any of Claims 1 to 3 comprising by weight about 70-95%
norfloxacin, about 2-30% disintegrant.
norfloxacin, about 2-30% disintegrant.
5. A tablet according to any of Claims 1 to 3 further comprising a lubricant.
6. A tablet according to Claim 5 wherein the amount of lubricant by weight is about 0.5% to 3%.
7. A tablet according to Claim 5 wherein the lubricant is magnesium stearate.
8. A tablet as in any Claims 1 to 7 wherein the amount of norfloxacin is about 400 mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2239931 CA2239931A1 (en) | 1998-07-15 | 1998-07-15 | Pharmaceutical tablet comprising norfloxacin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2239931 CA2239931A1 (en) | 1998-07-15 | 1998-07-15 | Pharmaceutical tablet comprising norfloxacin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2239931A1 true CA2239931A1 (en) | 2000-01-15 |
Family
ID=29275848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2239931 Abandoned CA2239931A1 (en) | 1998-07-15 | 1998-07-15 | Pharmaceutical tablet comprising norfloxacin |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2239931A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6521253B1 (en) | 1998-09-03 | 2003-02-18 | Astrazeneca Ab | Immediate release tablet |
| WO2003103674A1 (en) * | 2002-06-06 | 2003-12-18 | Bernard Charles Sherman | Tablets comprising ciprofloxacin hydrochloride |
| EP1501485B1 (en) | 2002-04-23 | 2007-09-26 | Novartis AG | High drug load tablet |
| WO2014146775A1 (en) * | 2013-03-19 | 2014-09-25 | Pharmathen S.A. | Pharmaceutical composition comprising a fluoroquinolone antibacterial agent and method for the preparation thereof |
-
1998
- 1998-07-15 CA CA 2239931 patent/CA2239931A1/en not_active Abandoned
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6521253B1 (en) | 1998-09-03 | 2003-02-18 | Astrazeneca Ab | Immediate release tablet |
| US6875446B2 (en) | 1998-09-03 | 2005-04-05 | Astrazeneca Ab | Method for prophylaxis and/or treatment of thromboembolism |
| EP1501485B1 (en) | 2002-04-23 | 2007-09-26 | Novartis AG | High drug load tablet |
| WO2003103674A1 (en) * | 2002-06-06 | 2003-12-18 | Bernard Charles Sherman | Tablets comprising ciprofloxacin hydrochloride |
| WO2014146775A1 (en) * | 2013-03-19 | 2014-09-25 | Pharmathen S.A. | Pharmaceutical composition comprising a fluoroquinolone antibacterial agent and method for the preparation thereof |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |