CA1339194C - Mixture of alginates and polyacrylates and its use - Google Patents
Mixture of alginates and polyacrylates and its useInfo
- Publication number
- CA1339194C CA1339194C CA000593385A CA593385A CA1339194C CA 1339194 C CA1339194 C CA 1339194C CA 000593385 A CA000593385 A CA 000593385A CA 593385 A CA593385 A CA 593385A CA 1339194 C CA1339194 C CA 1339194C
- Authority
- CA
- Canada
- Prior art keywords
- tablet
- polyacrylate
- alginate
- alkyl
- alginates
- 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.)
- Expired - Lifetime
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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/04—Alginic acid; Derivatives thereof
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)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Separation Of Suspended Particles By Flocculating Agents (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Detergent Compositions (AREA)
Abstract
A mixture of an alginate and a polyacrylate in a ratio of from 15 : 1 to 1 : 2 is suitable for the preparation of depot drug forms.
Description
133919~
Mixture of alqinates and polyacrylates and its use The present invention relates to a mixture of alginates and polyacrylates and its use in the preparation 5 of depot drugs.
It is known that alginates can be used for the preparation of depot drugs (Pharm, Ind. 33 (1971), 296).
However, the use of alginates for this purpose often presents difficulties. For example, the formulations 10 frequently do not achieve sufficient hardness when tableted. Their abrasion is therefore very high, which presents problems during subsequent film coating.
Insufficient hardness leads to breaking during filling on filling machines. Furthermore, alginates readily absorb 15 water, which leads to swelling of the tablets or, in the case of film tablets, to cracking of the films, unless complete protection from moisture is ensured by complicated and expensive packaging.
Conventional alginate-based sustained-release 20 tablets show no plasma level having a pronounced plateau character, despite zero order in vitro release, and still show a pronounced and not always desirable plasma peak despite a substantial delay in the time of maximum plasma concentration compared with drug forms which release the 25 active compound rapidly.
It has now been found that these difficulties can be avoided if polyacrylates or polymethacrylates are mixed with alginates.
More particularly, the present invention as 30 broadly disclosed hereinafter relates to the use of a mixture of an alginate and a polymethacrylate or copolymer of acrylic and methacrylic acid in a ratio of from 15 :
1 to 1 : 2, preferably 9 : 1 to 2 : 1, for the preparation of depot drugs.
B
However, the invention as claimed is restricted to a tablet for sustained release of a drug selected from the group consisting of propafenone, barucainide, nesapidil, gallopamil and biperiden, said tablet being 5 composed of a blend of a unit dosage of said drug with a mixture of an alginate with a polyacrylate in a ratio of : 1 to 1 : 2, wherein said polyacrylate is the formula:
Rl R2 --CH2--f--CH2--1--fo fo ~13 (i~ 4 -- m 15 where R1 is C1-C4-alkyl, R2 is hydrogen or C1-C4-alkyl, R3 is hydrogen, C1-C4-alkyl or a radical -(CH2)n-NR5R6 or -(CH2) n~
N~R5R6R7 Cle, where n is from 1 to 4 and R5, R6 and R7 are each hydrogen or C1-C4-alkyl, R4 is hydrogen or C1-C4-alkyl and m is from 500 to 1,500.
Particularly suitable alginates that can be used herein are propylene glycol alginates and alkali and alkaline earth metal alginates, in particular the sodium, potassium, ammonium and calcium alginates. These alginates are described for example, in the book by Roy L.
z5 Whistler, Industrial Gums, New York, 1973, in the subsection by McNeely and Pettitt on alginates. They are mainly used as gel formers or thickeners in food technology, in the printing, textile and paper industries and in welding electrodes.
30As aforesaid, particularly suitable polyacrylates are those of the formula:
I t R 2 --CH 2 - f - cH 2--f--CO CO
-- m where R1 is C1-C4-alkyl, RZ is hydrogen or C1-C4-alkyl, R3 is hydrogen, C1-C4-alkyl or a radical -(CH2)n-NR5R6 or -~CH2)n-N~R5R6R7 Cle, where n is from 1 to 4 and R5, R6 and R7 are each hydrogen or C1-C4-alkyl, R~ is hydrogen or 5 C1-C4-alkyl and m is from 500 to 1,500.
If the polyacrylate is used in the form of the ammonium salt (R3 = -(CH2)n-N~R5R6R7 Cl~), m is preferably from 7,000 to 11,000, in particular from 8,000 to 10,000.
In the other cases, m is preferably from 700 to 1,000.
Such methacrylates and copolymers are described in, for example, Houben-Weyl, Methoden der organischen Chemie, Thieme-Verlag, Stuttgart, 1961. Products which are commercially available under the trade mark EUDRAGIT~
are particularly suitable. The EUDRAGIT~ products include 15 different species respectively called EUDRAGIT~ E, L/S, RS, RL/RS, NED, LD in the advertising brochure of their manufacture, Rohm Pharma GmbH, Darmstadt.
In accordance with a particularly preferred embodiment of the invention, use is made of the EUDRAGIT~
20 RS product.
The novel mixture of alginate and polyacrylate is particularly suitable for the preparation of oral depot forms (viz. tablets) of propafenone, barucainide, nesapidil, gallopamil and biperiden.
The use of this novel mixture has the following advantages:
1. The release of the active compound from the drug forms is substantially linear.
Mixture of alqinates and polyacrylates and its use The present invention relates to a mixture of alginates and polyacrylates and its use in the preparation 5 of depot drugs.
It is known that alginates can be used for the preparation of depot drugs (Pharm, Ind. 33 (1971), 296).
However, the use of alginates for this purpose often presents difficulties. For example, the formulations 10 frequently do not achieve sufficient hardness when tableted. Their abrasion is therefore very high, which presents problems during subsequent film coating.
Insufficient hardness leads to breaking during filling on filling machines. Furthermore, alginates readily absorb 15 water, which leads to swelling of the tablets or, in the case of film tablets, to cracking of the films, unless complete protection from moisture is ensured by complicated and expensive packaging.
Conventional alginate-based sustained-release 20 tablets show no plasma level having a pronounced plateau character, despite zero order in vitro release, and still show a pronounced and not always desirable plasma peak despite a substantial delay in the time of maximum plasma concentration compared with drug forms which release the 25 active compound rapidly.
It has now been found that these difficulties can be avoided if polyacrylates or polymethacrylates are mixed with alginates.
More particularly, the present invention as 30 broadly disclosed hereinafter relates to the use of a mixture of an alginate and a polymethacrylate or copolymer of acrylic and methacrylic acid in a ratio of from 15 :
1 to 1 : 2, preferably 9 : 1 to 2 : 1, for the preparation of depot drugs.
B
However, the invention as claimed is restricted to a tablet for sustained release of a drug selected from the group consisting of propafenone, barucainide, nesapidil, gallopamil and biperiden, said tablet being 5 composed of a blend of a unit dosage of said drug with a mixture of an alginate with a polyacrylate in a ratio of : 1 to 1 : 2, wherein said polyacrylate is the formula:
Rl R2 --CH2--f--CH2--1--fo fo ~13 (i~ 4 -- m 15 where R1 is C1-C4-alkyl, R2 is hydrogen or C1-C4-alkyl, R3 is hydrogen, C1-C4-alkyl or a radical -(CH2)n-NR5R6 or -(CH2) n~
N~R5R6R7 Cle, where n is from 1 to 4 and R5, R6 and R7 are each hydrogen or C1-C4-alkyl, R4 is hydrogen or C1-C4-alkyl and m is from 500 to 1,500.
Particularly suitable alginates that can be used herein are propylene glycol alginates and alkali and alkaline earth metal alginates, in particular the sodium, potassium, ammonium and calcium alginates. These alginates are described for example, in the book by Roy L.
z5 Whistler, Industrial Gums, New York, 1973, in the subsection by McNeely and Pettitt on alginates. They are mainly used as gel formers or thickeners in food technology, in the printing, textile and paper industries and in welding electrodes.
30As aforesaid, particularly suitable polyacrylates are those of the formula:
I t R 2 --CH 2 - f - cH 2--f--CO CO
-- m where R1 is C1-C4-alkyl, RZ is hydrogen or C1-C4-alkyl, R3 is hydrogen, C1-C4-alkyl or a radical -(CH2)n-NR5R6 or -~CH2)n-N~R5R6R7 Cle, where n is from 1 to 4 and R5, R6 and R7 are each hydrogen or C1-C4-alkyl, R~ is hydrogen or 5 C1-C4-alkyl and m is from 500 to 1,500.
If the polyacrylate is used in the form of the ammonium salt (R3 = -(CH2)n-N~R5R6R7 Cl~), m is preferably from 7,000 to 11,000, in particular from 8,000 to 10,000.
In the other cases, m is preferably from 700 to 1,000.
Such methacrylates and copolymers are described in, for example, Houben-Weyl, Methoden der organischen Chemie, Thieme-Verlag, Stuttgart, 1961. Products which are commercially available under the trade mark EUDRAGIT~
are particularly suitable. The EUDRAGIT~ products include 15 different species respectively called EUDRAGIT~ E, L/S, RS, RL/RS, NED, LD in the advertising brochure of their manufacture, Rohm Pharma GmbH, Darmstadt.
In accordance with a particularly preferred embodiment of the invention, use is made of the EUDRAGIT~
20 RS product.
The novel mixture of alginate and polyacrylate is particularly suitable for the preparation of oral depot forms (viz. tablets) of propafenone, barucainide, nesapidil, gallopamil and biperiden.
The use of this novel mixture has the following advantages:
1. The release of the active compound from the drug forms is substantially linear.
2. The tablet cores are very hard and abrasion-resistant, so that they can be further processed without difficulties.
13391~9 3a 3.The hygroscopicity of the alginates is no longer disadvantageous during tablet preparation. The tablet-ing mixtures can be pressed directly without granula-tion, and the expensive and complicated wet granulationcan be avoided. Film tablets no longer require any special protection from moisture and no longer crack during open storage for a short time.
13391~9 3a 3.The hygroscopicity of the alginates is no longer disadvantageous during tablet preparation. The tablet-ing mixtures can be pressed directly without granula-tion, and the expensive and complicated wet granulationcan be avoided. Film tablets no longer require any special protection from moisture and no longer crack during open storage for a short time.
4.After administration of the novel drug forms, the plasma level of active compound has a pronounced plateau character and a substantially flatter curve than after administration of drug forms which are only based on alginates.
The Examples which follow illustrate the invention.
Tablets having the following composition (in mg) were prepared in a conventional manner:
A B C D E F
Gallopamil.HCl 100 100 100 100 100 100 Na alginate 300 240 200 166 132 332 ~udragit E 32 92 132 166 200 0 Mg stearate 4 4 4 4 4 4 Cellulose powder31 31 31 31 31 31 For this purpose, gallopamil.HCl, Na alginate and ~udragit E are dry-blended in a mixer, moistened with an aqueous solution of PVP or PVP/PVA copolymers ~ ollidon 30, ~ollidon 25 or @kollidon VA 64) while stirring, forced through a sieve and dried in a fluidized-bed drier, passed again through a ~ieve and mixed with Mg stearate and cellulose powder. The mixtures were pressed to give tablets weighing 480 mg.
Barucainide was processed similarly.
The hardness of the tablets was determined using the ~harmatest hardness tester and their abrasion was measured with the~Pharmatest friabilator (400 revolutions in 13 minutes).
The following results were obtained:
Tablets A B C D E F
Hardness (N) 104 122 137 103 84 61 Abrasion (%) 0.1 0.1 0.1 1.0 1.0 3.8 Similar values were obtained when gallopamil was replaced with another active compound, eg. barucainide, or another ~Eudragit (eg. 6~udragit RS) was used instead - of ~Eudragit E.
If the mixtures A to F of Example 1 are pressed directly without granulation to give tablets, the result-ing tablets have a hardness of from 70 to 110 N. Mixture F, however, gives unusable tablets having a hardness of - only 10 N.
Tablets having the following composition (in mg) 20 were prepared similarly to Example 1:
G H
Gallopamil 100 100 Na alginate 267 267 ~Eudragit RS 67 Mg stearate 4 4 Cellulose powder 29 29 Tablets G had a hardness of 120 N and tablets H
had a hardness of 78 N. The corresponding values for the friability were 0.05% and 2.1%, respectively.
If the tablets are produced by direct compres-sion, ie. without granulation, tablets having a hardness of 100 N tG) or 13 N (H) are obtained. -Testing the tablets Test persons each received 1 tablet G or H (cf.Example 3). Blood samples were then taken at certain 133~1 9~
time intervals and the content of gallopamil therein was det~ ined:
Time (h) 0.5 1 2 3 4 6 8 10 12 G (ng/ml of plasma) 0.7 0.94.6 6.8 10 9.0 8.9 8.2 5.9 H (ng/ml of plasma) 3.8 10 29 33 36 17 10 6.4 6.9 In contrast to H, G has a substantially flatter plasma level curve.
_~, . 10 EXAMPLE 4 Tablets having the following composition (in mg) were prepared:
J R
Propafenone.HCl 600 600 Na alginate 253 253 @Eudragit RS 53 Cellulose 11 11 Mg stearate 3 3 The preparation was carried out by moist granu-lation of a mixture of propafenone and alginate (in case - J also with ~udragit) with an aqueous PVP solution and subsequent addition of cellulose and Mg stearate to the - 25 dried granules. The granules were converted into tablets -~ similarly to Example 1.
In case J, the tablets obtained had a hardness of 165 N and their friability was virtually impossible to measure. In case R, the tablets obtained were unusable and did not withstand subsequent film coating without giving a fairly large amount of fragments. The applica-tion of a rapidly dissolving film is absolutely essential for masking the extremely bitter flavor of propafenone.
The Examples which follow illustrate the invention.
Tablets having the following composition (in mg) were prepared in a conventional manner:
A B C D E F
Gallopamil.HCl 100 100 100 100 100 100 Na alginate 300 240 200 166 132 332 ~udragit E 32 92 132 166 200 0 Mg stearate 4 4 4 4 4 4 Cellulose powder31 31 31 31 31 31 For this purpose, gallopamil.HCl, Na alginate and ~udragit E are dry-blended in a mixer, moistened with an aqueous solution of PVP or PVP/PVA copolymers ~ ollidon 30, ~ollidon 25 or @kollidon VA 64) while stirring, forced through a sieve and dried in a fluidized-bed drier, passed again through a ~ieve and mixed with Mg stearate and cellulose powder. The mixtures were pressed to give tablets weighing 480 mg.
Barucainide was processed similarly.
The hardness of the tablets was determined using the ~harmatest hardness tester and their abrasion was measured with the~Pharmatest friabilator (400 revolutions in 13 minutes).
The following results were obtained:
Tablets A B C D E F
Hardness (N) 104 122 137 103 84 61 Abrasion (%) 0.1 0.1 0.1 1.0 1.0 3.8 Similar values were obtained when gallopamil was replaced with another active compound, eg. barucainide, or another ~Eudragit (eg. 6~udragit RS) was used instead - of ~Eudragit E.
If the mixtures A to F of Example 1 are pressed directly without granulation to give tablets, the result-ing tablets have a hardness of from 70 to 110 N. Mixture F, however, gives unusable tablets having a hardness of - only 10 N.
Tablets having the following composition (in mg) 20 were prepared similarly to Example 1:
G H
Gallopamil 100 100 Na alginate 267 267 ~Eudragit RS 67 Mg stearate 4 4 Cellulose powder 29 29 Tablets G had a hardness of 120 N and tablets H
had a hardness of 78 N. The corresponding values for the friability were 0.05% and 2.1%, respectively.
If the tablets are produced by direct compres-sion, ie. without granulation, tablets having a hardness of 100 N tG) or 13 N (H) are obtained. -Testing the tablets Test persons each received 1 tablet G or H (cf.Example 3). Blood samples were then taken at certain 133~1 9~
time intervals and the content of gallopamil therein was det~ ined:
Time (h) 0.5 1 2 3 4 6 8 10 12 G (ng/ml of plasma) 0.7 0.94.6 6.8 10 9.0 8.9 8.2 5.9 H (ng/ml of plasma) 3.8 10 29 33 36 17 10 6.4 6.9 In contrast to H, G has a substantially flatter plasma level curve.
_~, . 10 EXAMPLE 4 Tablets having the following composition (in mg) were prepared:
J R
Propafenone.HCl 600 600 Na alginate 253 253 @Eudragit RS 53 Cellulose 11 11 Mg stearate 3 3 The preparation was carried out by moist granu-lation of a mixture of propafenone and alginate (in case - J also with ~udragit) with an aqueous PVP solution and subsequent addition of cellulose and Mg stearate to the - 25 dried granules. The granules were converted into tablets -~ similarly to Example 1.
In case J, the tablets obtained had a hardness of 165 N and their friability was virtually impossible to measure. In case R, the tablets obtained were unusable and did not withstand subsequent film coating without giving a fairly large amount of fragments. The applica-tion of a rapidly dissolving film is absolutely essential for masking the extremely bitter flavor of propafenone.
Claims (8)
1. A tablet for sustained release of a drug selected from the group consisting of propafenone, barucainide, nesapidil, gallopamil and biperiden, said tablet being composed of a blend of a unit dosage of said drug with a mixture of an alginate with a polyacrylate in a ratio of 15 : 1 to 1 : 2, wherein said polyacrylate is the formula:
where R1 is C1-C4-alkyl, R2 is hydrogen or C1-C4-alkyl, R3 is hydrogen, C1-C4-alkyl or a radical -(CH2)n-NR5R6 or -(CH2) n-N~R5R6R7 Cl~, where n is from 1 to 4 and R5, R6 and R7 are each hydrogen or C1-C4-alkyl, R4 is hydrogen or C1-C4-alkyl and m is from 500 to 1,500.
where R1 is C1-C4-alkyl, R2 is hydrogen or C1-C4-alkyl, R3 is hydrogen, C1-C4-alkyl or a radical -(CH2)n-NR5R6 or -(CH2) n-N~R5R6R7 Cl~, where n is from 1 to 4 and R5, R6 and R7 are each hydrogen or C1-C4-alkyl, R4 is hydrogen or C1-C4-alkyl and m is from 500 to 1,500.
2. The tablet of claim 1, wherein the drug is gallopamil and the ratio of alginate to polyacrylate is ranging from 15 : 1 to 2 : 1.
3. The tablet of claim 1, wherein the drug is propafenone and the ratio of alginate to polyacrylate is ranging from 15 : 1 to 2 : 1.
4. The tablet claim 1, 2 or 3, wherein said polyacrylate is the one commercially available under the trade mark EUDRAGIT R RS.
5. The tablet of claim 1, 2 or 3, wherein the ratio of alginate to polyacrylate is ranging from 9 : 1 to 2 : 1.
6. The tablet of claim 5, wherein the alginate is selected from the group consisting of propylene glycol alginates and alkali and alkaline earth metal alginates.
7. The tablet of claim 5, wherein said polyacrylate is the one commercially available under the trade mark EUDRAGIT R RS.
8. The tablet of claim 6, wherein said polyacrylate is the one commercially available under the trade mark EUDRAGIT R RS.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3809764A DE3809764A1 (en) | 1988-03-23 | 1988-03-23 | MIXTURE OF ALGINATES AND POLYACRYLATES AND THEIR USE |
| DEP3809764.8 | 1988-03-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1339194C true CA1339194C (en) | 1997-08-05 |
Family
ID=6350476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000593385A Expired - Lifetime CA1339194C (en) | 1988-03-23 | 1989-03-10 | Mixture of alginates and polyacrylates and its use |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0334167B1 (en) |
| JP (1) | JP2901635B2 (en) |
| AT (1) | ATE89580T1 (en) |
| BR (1) | BR1100435A (en) |
| CA (1) | CA1339194C (en) |
| DE (2) | DE3809764A1 (en) |
| DK (1) | DK174299B1 (en) |
| ES (1) | ES2054906T3 (en) |
| FI (1) | FI102184B1 (en) |
| HU (1) | HU211743A9 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR920002912B1 (en) * | 1990-03-27 | 1992-04-10 | 재단법인 한국화학연구소 | Process for preparing the resin having bio-degradation and its mixture |
| DE4120049C2 (en) * | 1990-06-18 | 1996-04-11 | Tokuyama Corp | Impression material |
| DE4204012A1 (en) * | 1992-02-12 | 1993-08-19 | Ulrich Prof Dr Zimmermann | MITOGEN-FREE SUBSTANCE, THEIR PRODUCTION AND USE |
| IL109097A0 (en) * | 1993-04-03 | 1994-06-24 | Knoll Ag | Delayed release micro tablet of beta-phenylpropiophenone derivatives and its production |
| DE4443358A1 (en) * | 1994-12-06 | 1996-06-13 | Basf Ag | Depot medication |
| FR2752843B1 (en) * | 1996-08-30 | 1998-10-16 | Sod Conseils Rech Applic | CROSSLINKED COPOLYMERS BASED ON POLYCARBOXYLIC POLYMERS AND THEIR USE AS SUPPORTS OF PHARMACEUTICAL COMPOSITIONS |
| US6229009B1 (en) | 1997-08-29 | 2001-05-08 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Polycarboxylic based cross-linked copolymers |
| WO2000045793A1 (en) * | 1999-02-04 | 2000-08-10 | Abbott Laboratories | Ph independent extended release pharmaceutical formulation |
| US6150410A (en) * | 1999-02-04 | 2000-11-21 | Abbott Laboratories | pH independent extended release pharmaceutical formulation |
| DE102007009242A1 (en) * | 2007-02-22 | 2008-09-18 | Evonik Röhm Gmbh | Pellets with enteric-coated matix |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1566935A (en) * | 1977-05-23 | 1980-05-08 | Ici Ltd | Thickening agents |
| DE3113901A1 (en) * | 1981-04-07 | 1982-10-28 | Basf Ag, 6700 Ludwigshafen | ACTIVE SUBSTANCE PREPARATION FOR ORAL APPLICATION |
| DE3580384D1 (en) * | 1984-04-09 | 1990-12-13 | Toyo Boseki | PREPARATION WITH DELAYED RELEASE FOR APPLICATION ON THE ORIGINAL SLIME. |
| GB8521494D0 (en) * | 1985-08-29 | 1985-10-02 | Zyma Sa | Controlled release tablet |
| JPH0794384B2 (en) * | 1986-09-01 | 1995-10-11 | 帝国製薬株式会社 | Sustained-release oral formulation |
| KR960011236B1 (en) * | 1987-05-08 | 1996-08-21 | 스미스 클라인 앤드 프렌취 라보라토리스 리미티드 | Pharmaceutical compositions of cimetidine |
-
1988
- 1988-03-23 DE DE3809764A patent/DE3809764A1/en not_active Withdrawn
-
1989
- 1989-03-10 CA CA000593385A patent/CA1339194C/en not_active Expired - Lifetime
- 1989-03-14 DE DE8989104502T patent/DE58904383D1/en not_active Expired - Lifetime
- 1989-03-14 AT AT89104502T patent/ATE89580T1/en not_active IP Right Cessation
- 1989-03-14 ES ES89104502T patent/ES2054906T3/en not_active Expired - Lifetime
- 1989-03-14 EP EP89104502A patent/EP0334167B1/en not_active Expired - Lifetime
- 1989-03-20 JP JP1066441A patent/JP2901635B2/en not_active Expired - Lifetime
- 1989-03-21 FI FI891329A patent/FI102184B1/en not_active IP Right Cessation
- 1989-03-22 DK DK198901427A patent/DK174299B1/en not_active IP Right Cessation
-
1995
- 1995-06-30 HU HU95P/P00712P patent/HU211743A9/en unknown
-
1997
- 1997-05-05 BR BR1100435-5A patent/BR1100435A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| FI891329A (en) | 1989-09-24 |
| FI891329A0 (en) | 1989-03-21 |
| JP2901635B2 (en) | 1999-06-07 |
| DK142789D0 (en) | 1989-03-22 |
| ATE89580T1 (en) | 1993-06-15 |
| EP0334167B1 (en) | 1993-05-19 |
| BR1100435A (en) | 1999-12-07 |
| JPH026543A (en) | 1990-01-10 |
| DK142789A (en) | 1989-09-24 |
| DE58904383D1 (en) | 1993-06-24 |
| FI102184B (en) | 1998-10-30 |
| DE3809764A1 (en) | 1989-10-05 |
| EP0334167A1 (en) | 1989-09-27 |
| FI102184B1 (en) | 1998-10-30 |
| HU211743A9 (en) | 1995-12-28 |
| DK174299B1 (en) | 2002-11-25 |
| ES2054906T3 (en) | 1994-08-16 |
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Effective date: 20140805 |