CA2469327A1 - Propafenone hydrochloride capsules containing microtablets - Google Patents
Propafenone hydrochloride capsules containing microtablets Download PDFInfo
- Publication number
- CA2469327A1 CA2469327A1 CA002469327A CA2469327A CA2469327A1 CA 2469327 A1 CA2469327 A1 CA 2469327A1 CA 002469327 A CA002469327 A CA 002469327A CA 2469327 A CA2469327 A CA 2469327A CA 2469327 A1 CA2469327 A1 CA 2469327A1
- Authority
- CA
- Canada
- Prior art keywords
- microtablets
- propafenone hydrochloride
- capsules
- lubricant
- weight
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Abstract
A capsule for oral administration of propafenone hydrochloride, wherein the capsule contains microtablets, and wherein the amount of lubricant, if any, comprises less than 0.1% of the weight of the microtablets.
Description
PROPAFENQNE HYDROCHI ORIDE CAPSULES
CONTAINING MICR TABLETS
Background Propafenone hydrochloride is an antiarrythmic agent sold in the United States and elsewhere under the tradename RythmoITM, in the form of immediate-release tablets in strengths of 150 mg, 225 mg and 300 mg. The usual dosing schedule is 3 times daily.
In early 2004, propafenone hydrochloride also became available in the United States and elsewhere under the tradename Rythmol SRTM in the form of sustained release capsules in strengths of 225 mg, 325 mg and 425 mg. Because the release from Rythmol SRTM is gradual over many hours after ingestion, the dosing schedule for Rythmol SR'~'~" is only twice daily, which is more convenient for the patient.
Rythmol SR'A'M capsules are made in accordance with the disclosure of US
patent 5,681,588. As explained in the disclosure of that patent, the manufacture of sustained release dosage forms usually requires relatively large quantities of excipients (inactive ingredients). This makes it difficult to produce tablets or capsules that contain relatively large amounts of active ingredients but are still small in size.
The disclosure further explains that it was surprisingly found that satisfactory sustained release is achieved from microtablets wherein propafenone hydrochloride comprises from 81 to 99.9% of the weight of the microtablets. Gelatin capsules are filled with these microtablets.
TM _ Trademark The microtablets actually contained in Rythmoi SRTM capsules have a propafenone hydrochloride content of 6.25 mg per microtablet, and a total weight of 6.5 mg per microtablet. Propafenone hydrochloride thus comprises about 96% of the weight of the microtablets. Because the propafenone hydrochloride content is 6.25 mg per microtablet, it follows that the number of microtablets required per capsule is 36 for 225 mg capsules, 52 for 325 mg capsules, and 68 for 425 mg capsules.
Because the propafenone hydrochloride comprises only 96% of the weight of the i0 microtablets in Rythmol SRTM capsules, the microtablsts are larger than would be required if the propafenone hydrochloride content were 100°, with the result that the maximum dose can be included in a capsule of any given size is somewhat less than would be achieved if propafenone hydrochloride comprised 100% of the weight of the microtablets. The need to include excipients also increases the cost.
According to the disclosure of U.S. patent 5,681,588, the reason that the propafenone hydrochloride content must be less than 100%, is that a lubricant at a level of O.t% to 5% must be added as an aid in the tabletting process; i:e. to avoid sticking to the tooling in the process of forming the microtablets on a tablet press.
Also, the inclusion of a lubricant somewhat softens the tablets, with the result that a binder must be included to enable tablets of adequate hardness. All of the examples of microtablets in U.S. patent 5,681,588 include hydroxypropylmethylcellulose as binder.
CONTAINING MICR TABLETS
Background Propafenone hydrochloride is an antiarrythmic agent sold in the United States and elsewhere under the tradename RythmoITM, in the form of immediate-release tablets in strengths of 150 mg, 225 mg and 300 mg. The usual dosing schedule is 3 times daily.
In early 2004, propafenone hydrochloride also became available in the United States and elsewhere under the tradename Rythmol SRTM in the form of sustained release capsules in strengths of 225 mg, 325 mg and 425 mg. Because the release from Rythmol SRTM is gradual over many hours after ingestion, the dosing schedule for Rythmol SR'~'~" is only twice daily, which is more convenient for the patient.
Rythmol SR'A'M capsules are made in accordance with the disclosure of US
patent 5,681,588. As explained in the disclosure of that patent, the manufacture of sustained release dosage forms usually requires relatively large quantities of excipients (inactive ingredients). This makes it difficult to produce tablets or capsules that contain relatively large amounts of active ingredients but are still small in size.
The disclosure further explains that it was surprisingly found that satisfactory sustained release is achieved from microtablets wherein propafenone hydrochloride comprises from 81 to 99.9% of the weight of the microtablets. Gelatin capsules are filled with these microtablets.
TM _ Trademark The microtablets actually contained in Rythmoi SRTM capsules have a propafenone hydrochloride content of 6.25 mg per microtablet, and a total weight of 6.5 mg per microtablet. Propafenone hydrochloride thus comprises about 96% of the weight of the microtablets. Because the propafenone hydrochloride content is 6.25 mg per microtablet, it follows that the number of microtablets required per capsule is 36 for 225 mg capsules, 52 for 325 mg capsules, and 68 for 425 mg capsules.
Because the propafenone hydrochloride comprises only 96% of the weight of the i0 microtablets in Rythmol SRTM capsules, the microtablsts are larger than would be required if the propafenone hydrochloride content were 100°, with the result that the maximum dose can be included in a capsule of any given size is somewhat less than would be achieved if propafenone hydrochloride comprised 100% of the weight of the microtablets. The need to include excipients also increases the cost.
According to the disclosure of U.S. patent 5,681,588, the reason that the propafenone hydrochloride content must be less than 100%, is that a lubricant at a level of O.t% to 5% must be added as an aid in the tabletting process; i:e. to avoid sticking to the tooling in the process of forming the microtablets on a tablet press.
Also, the inclusion of a lubricant somewhat softens the tablets, with the result that a binder must be included to enable tablets of adequate hardness. All of the examples of microtablets in U.S. patent 5,681,588 include hydroxypropylmethylcellulose as binder.
In light of the foregoing, the objective to the present invention is to enable sustained release propafenone hydrochloride capsules containing microtablets, wherein the excipient content is less than required according to the disclosure of U.S.
patent 5,681,588.
Descriution of thg, Invention It has surprisingly been found that pure propafenone hydrochloride, with no excipients added, exhibits relatively little tendency to stick to tooling in a tabletting process, particularly if the tooling has flat faces (i.e. no concavity). This means that, contrary to what is taught by U.S. patent 5,681,588, it is not necessary to inGude in the tablet 0.1 % or more of a lubricant. Instead, tablets can be made with less than 0.1 % by weight of a lubricant, or even no lubricant at all.
The nrduction or elimination of a lubricant also has the benefit of increasing tablet hardness, so as to reduce or eliminate the need for a binder.
Accordingly, compositions of the present invention are sustained release propafenone hydrochloride capsules for oral administration containing microtablets, wherein the quantity of lubricant, if any, is less than 0.1 % of the microtablets by weight. The microtablets will preferably be lubricant free.
For the purposes of the present disclosure and claims, the word "microtablet"
will be defined as meaning a tablet of weight between 2 mg and 30 mg.
i The microtablets will optionally contain up to 10 percent by weight of a binder, such as, for example, povidone, copovidone, cellulose, or a cellulose derivative.
However, the microtabl~ts will preferably be free of a binder.
The microtablets will optionally also comprise other excipients.
Most preferably, the microtablets will be comprised entirely of propafenone hydrochiortde, with no added excipients at all.
The invention will be illustrated by the following example.
mple 1 Pure propafenone hydrochloride was compacted and then milled into small granules.
The granules were then compressed into microtablets of 12.5 mg weight on a rotary tablet press, using flat-faced tooling of diameter 7164 inch.
Size 0 elongated capsules were filled with 34 of these microtablets per capsule, to give a content of 425 mg of propafenone hydrochloride per capsule.
patent 5,681,588.
Descriution of thg, Invention It has surprisingly been found that pure propafenone hydrochloride, with no excipients added, exhibits relatively little tendency to stick to tooling in a tabletting process, particularly if the tooling has flat faces (i.e. no concavity). This means that, contrary to what is taught by U.S. patent 5,681,588, it is not necessary to inGude in the tablet 0.1 % or more of a lubricant. Instead, tablets can be made with less than 0.1 % by weight of a lubricant, or even no lubricant at all.
The nrduction or elimination of a lubricant also has the benefit of increasing tablet hardness, so as to reduce or eliminate the need for a binder.
Accordingly, compositions of the present invention are sustained release propafenone hydrochloride capsules for oral administration containing microtablets, wherein the quantity of lubricant, if any, is less than 0.1 % of the microtablets by weight. The microtablets will preferably be lubricant free.
For the purposes of the present disclosure and claims, the word "microtablet"
will be defined as meaning a tablet of weight between 2 mg and 30 mg.
i The microtablets will optionally contain up to 10 percent by weight of a binder, such as, for example, povidone, copovidone, cellulose, or a cellulose derivative.
However, the microtabl~ts will preferably be free of a binder.
The microtablets will optionally also comprise other excipients.
Most preferably, the microtablets will be comprised entirely of propafenone hydrochiortde, with no added excipients at all.
The invention will be illustrated by the following example.
mple 1 Pure propafenone hydrochloride was compacted and then milled into small granules.
The granules were then compressed into microtablets of 12.5 mg weight on a rotary tablet press, using flat-faced tooling of diameter 7164 inch.
Size 0 elongated capsules were filled with 34 of these microtablets per capsule, to give a content of 425 mg of propafenone hydrochloride per capsule.
Claims (3)
1. A capsule for oral administration containing microtablets, wherein the microtablets comprise propafenone hydrochloride, and wherein the amount of lubricant, if any, comprises less than 0.1% of the weight of the microtablets.
2. A capsule of claim 1 wherein the microtablets are free of lubricant.
3. A capsule of claim 2 wherein the microtablets contain no excipients.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002469327A CA2469327A1 (en) | 2004-06-07 | 2004-06-07 | Propafenone hydrochloride capsules containing microtablets |
| PCT/CA2005/000863 WO2005120481A1 (en) | 2004-06-07 | 2005-06-03 | Propafenone hydrochloride capsules containing microtablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002469327A CA2469327A1 (en) | 2004-06-07 | 2004-06-07 | Propafenone hydrochloride capsules containing microtablets |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2469327A1 true CA2469327A1 (en) | 2005-12-07 |
Family
ID=35478487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002469327A Abandoned CA2469327A1 (en) | 2004-06-07 | 2004-06-07 | Propafenone hydrochloride capsules containing microtablets |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA2469327A1 (en) |
| WO (1) | WO2005120481A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010043950A2 (en) | 2008-10-15 | 2010-04-22 | Aizant Drug Research Solutions Private Limited | Propafenone extended release composition |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4547358A (en) * | 1980-05-06 | 1985-10-15 | Mead Johnson & Company | Sustained release tablet containing at least 95 percent theophylline |
| IL109097A0 (en) * | 1993-04-03 | 1994-06-24 | Knoll Ag | Delayed release micro tablet of beta-phenylpropiophenone derivatives and its production |
| US5733578A (en) * | 1995-11-15 | 1998-03-31 | Edward Mendell Co., Inc. | Directly compressible high load acetaminophen formulations |
-
2004
- 2004-06-07 CA CA002469327A patent/CA2469327A1/en not_active Abandoned
-
2005
- 2005-06-03 WO PCT/CA2005/000863 patent/WO2005120481A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005120481A1 (en) | 2005-12-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |