US20050202089A1 - Sustained-release pharmaceutical formulations containing mizolastine - Google Patents
Sustained-release pharmaceutical formulations containing mizolastine Download PDFInfo
- Publication number
- US20050202089A1 US20050202089A1 US11/027,680 US2768005A US2005202089A1 US 20050202089 A1 US20050202089 A1 US 20050202089A1 US 2768005 A US2768005 A US 2768005A US 2005202089 A1 US2005202089 A1 US 2005202089A1
- Authority
- US
- United States
- Prior art keywords
- mizolastine
- sustained
- release
- tablet
- organic acid
- 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
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to novel sustained-release pharmaceutical formulations containing 2-[[1-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]piperid-4-yl]methylamino]-pyrimidin-4-ol or 2-[[1-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]piperid-4-yl]methylamino]-pyrimidine-4(1H)-one, or mizolastine, as active principle.
- Mizolastine is described in European patent EP 0,217,700.
- Mizolastine binds to the H 1 histamine receptor and inhibits the degranulation of mastocytes in vitro and in vivo. It can thus be used for the treatment of respiratory, cutaneous or ocular allergies and various allergic manifestations.
- the Applicant Company has based its research of such formulations on the study of the kinetics of dissolution of mizolastine.
- mizolastine is a weak base (pK 5.6) which is sparingly soluble in water (13 mg/l at neutral pH) but much more soluble at acidic pH (11 g/l at pH 3); the first gelatin capsules released 100% of mizolastine over 30 minutes in a dissolution medium at pH 2 whereas only 40% were dissolved at pH 6.8.
- the release of mizolastine from the sustained-release pharmaceutical form according to the invention did not need to be influenced by the differences in pH in the gastrointestinal tract.
- the aim of the present invention is to propose formulations containing mizolastine whose dissolution profile is as follows:
- the Applicant Company has shown that tablets containing a core formed of a sustained-release tablet containing mizolastine combined with a fatty matrix and with an organic acid, the said tablet being coated to prevent degradation of the product by light, are entirely suitable.
- the tablets according to the invention contain from 1 mg to 25 mg of mizolastine. These doses correspond to concentrations of from 0.5% to 12% by weight of mizolastine.
- the fatty matrix is made with hydrogenated castor oil or with hydrogenated lecithins or long-chain fatty acids, for example C 12 -C 28 long chain fatty acids such as behenic acid, or triglycerides esterified with medium-chain fatty acids, for example C 8 -C 18 fatty acids.
- the organic acid preferably having a pK of 2 or more is chosen from maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acids in the form of racemates or isomers.
- the acid particularly preferred is L-tartaric acid.
- the weight ratio between the mizolastine and the organic acid should be between 0.3 and 1. With L-tartaric acid, this ratio is preferably equal to 0.5.
- the tablets are prepared by granulation using the active principle, the agent constituting the fatty matrix, the organic acid and other excipients such as, for example, lactose, mannitol and sugars or similar sugar-alcohols, microcrystalline cellulose, starch, calcium phosphates and sulphates, polyvidone, and substituted celluloses such as hydroxypropyl-cellulose, hydroxypropylmethylcellulose or methylcellulose.
- the agent constituting the fatty matrix
- the organic acid and other excipients such as, for example, lactose, mannitol and sugars or similar sugar-alcohols, microcrystalline cellulose, starch, calcium phosphates and sulphates, polyvidone, and substituted celluloses such as hydroxypropyl-cellulose, hydroxypropylmethylcellulose or methylcellulose.
- the granulation may be carried out in a wet phase, for example in the presence of water or alcohol, or may be performed by fusion or by compacting.
- the granulation step may optionally be left out and the tablets prepared by direct tableting of the mixture of mizolastine and the excipients.
- Anhydrous colloidal silica and magnesium stearate are added to the granules obtained and the mixture is tableted.
- the tablets are then covered with a coating film by spraying them with a coating solution in a machine with a fluidized-air bed or in a coating turbine.
- This profile gives about 50% of product dissolved in 1 hour, 100% of product dissolved in 3 to 5 hours, and it is independent of the pH.
- the plasma kinetics of a pharmaceutical form according to the invention containing 10 mg of mizolastine were studied in a healthy volunteer after a single oral administration, compared with a standard immediate-release gelatin capsule containing 10 mg of mizolastine.
- Table 1 presents the kinetic parameters and FIG. 3 the curves of the plasma kinetics, obtained respectively with each formulation; the plasma kinetics obtained with the pharmaceutical form according to the invention makes it possible to prevent any peak in the plasma without losing bioavailability.
- the plasma kinetics of a pharmaceutical form according to the invention were also studied in comparison with the same formulation without L-tartaric acid.
- Table 2 shows that the bioavailability of the formulation containing no L-tartaric acid represents only 43% of that observed with the formulation according to the invention containing L-tartaric acid.
- the values of Cmax and the AUC values (0- ⁇ ) are respectively 1.5 and 2 times as high for the formulation containing L-tartaric acid as for that not containing any.
Abstract
A sustained-release pharmaceutical formulation containing mizolastine, a core formed of a sustained-release table containing mizolastine combined with a fatty matrix and an organic acid, the tablet being coated.
Description
- The present invention relates to novel sustained-release pharmaceutical formulations containing 2-[[1-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]piperid-4-yl]methylamino]-pyrimidin-4-ol or 2-[[1-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]piperid-4-yl]methylamino]-pyrimidine-4(1H)-one, or mizolastine, as active principle.
- Mizolastine is described in European patent EP 0,217,700.
- Mizolastine binds to the H1 histamine receptor and inhibits the degranulation of mastocytes in vitro and in vivo. It can thus be used for the treatment of respiratory, cutaneous or ocular allergies and various allergic manifestations.
- During the oral administration of immediate-release formulations containing mizolastine, undesirable sedative effects have been observed which are associated with the existence of a high peak in the plasma.
- Consequently, it was necessary to find formulations for an oral administration which have a profile of release of the active principle such that it is possible to obtain a lower peak in the plasma without decreasing the bioavailability.
- The Applicant Company has based its research of such formulations on the study of the kinetics of dissolution of mizolastine. The reason for this is that mizolastine is a weak base (pK 5.6) which is sparingly soluble in water (13 mg/l at neutral pH) but much more soluble at acidic pH (11 g/l at pH 3); the first gelatin capsules released 100% of mizolastine over 30 minutes in a dissolution medium at pH 2 whereas only 40% were dissolved at pH 6.8.
- Moreover, the release of mizolastine from the sustained-release pharmaceutical form according to the invention did not need to be influenced by the differences in pH in the gastrointestinal tract.
- The aim of the present invention is to propose formulations containing mizolastine whose dissolution profile is as follows:
-
- about 30 to 70% of mizolastine dissolved in 1 hour,
- 100% of mizolastine dissolved in 3 to 5 hours, and
- pH-independent profile.
- The Applicant Company has shown that tablets containing a core formed of a sustained-release tablet containing mizolastine combined with a fatty matrix and with an organic acid, the said tablet being coated to prevent degradation of the product by light, are entirely suitable.
- The tablets according to the invention contain from 1 mg to 25 mg of mizolastine. These doses correspond to concentrations of from 0.5% to 12% by weight of mizolastine.
- The fatty matrix is made with hydrogenated castor oil or with hydrogenated lecithins or long-chain fatty acids, for example C12-C28 long chain fatty acids such as behenic acid, or triglycerides esterified with medium-chain fatty acids, for example C8-C18 fatty acids.
- The organic acid preferably having a pK of 2 or more is chosen from maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acids in the form of racemates or isomers. According to the invention, the acid particularly preferred is L-tartaric acid.
- The weight ratio between the mizolastine and the organic acid should be between 0.3 and 1. With L-tartaric acid, this ratio is preferably equal to 0.5.
- The tablets are prepared by granulation using the active principle, the agent constituting the fatty matrix, the organic acid and other excipients such as, for example, lactose, mannitol and sugars or similar sugar-alcohols, microcrystalline cellulose, starch, calcium phosphates and sulphates, polyvidone, and substituted celluloses such as hydroxypropyl-cellulose, hydroxypropylmethylcellulose or methylcellulose.
- The granulation may be carried out in a wet phase, for example in the presence of water or alcohol, or may be performed by fusion or by compacting. The granulation step may optionally be left out and the tablets prepared by direct tableting of the mixture of mizolastine and the excipients.
- Anhydrous colloidal silica and magnesium stearate are added to the granules obtained and the mixture is tableted. The tablets are then covered with a coating film by spraying them with a coating solution in a machine with a fluidized-air bed or in a coating turbine.
- The example which follows illustrates the invention without limiting it:
% (weight) Tablet mizolastine 4.8 hydrogenated castor oil 12.0 lactose 60.0 microcrystalline cellulose 9.6 L-tartaric acid 9.6 polyvidone 2.9 anhydrous colloidal silica 0.2 magnesium stearate 0.9 purified water Q.S. Total 100.0 Coating methylhydroxypropylcellulose 74.0 titanium dioxide (E171) 18.5 propylene glycol 7.5 purified water Q.S. Total 100.0 - The dissolution profile obtained with a formulation according to the invention is given in FIG. 1.
- This profile gives about 50% of product dissolved in 1 hour, 100% of product dissolved in 3 to 5 hours, and it is independent of the pH.
- The dissolution profile obtained with a formulation identical to that of the invention but containing no L-tartaric acid is given in FIG. 2.
- The plasma kinetics of a pharmaceutical form according to the invention containing 10 mg of mizolastine were studied in a healthy volunteer after a single oral administration, compared with a standard immediate-release gelatin capsule containing 10 mg of mizolastine.
- Table 1 presents the kinetic parameters and FIG. 3 the curves of the plasma kinetics, obtained respectively with each formulation; the plasma kinetics obtained with the pharmaceutical form according to the invention makes it possible to prevent any peak in the plasma without losing bioavailability.
- The plasma kinetics of a pharmaceutical form according to the invention were also studied in comparison with the same formulation without L-tartaric acid.
- The study was performed on twelve healthy volunteers after a single oral administration of a tablet according to the invention containing 10 mg of mizolastine or the same tablet without L-tartaric acid.
- Table 2 shows that the bioavailability of the formulation containing no L-tartaric acid represents only 43% of that observed with the formulation according to the invention containing L-tartaric acid. The values of Cmax and the AUC values (0-∞) are respectively 1.5 and 2 times as high for the formulation containing L-tartaric acid as for that not containing any.
- In addition, for the formulation with L-tartaric acid, the min.-max. variation indices are much lower, which suggests great uniformity in the release.
- The results altogether show that the formulations according to the invention have:
-
- a pH-independent dissolution profile,
- an in vivo release which prevents any peak in the plasma,
- a bioavailability which is not decreased relative to an immediate-release formulation,
- lower variability of the plasma kinetics results.
Claims (24)
1-7. (canceled)
8. A coated sustained release tablet, consisting essentially of from 0.5% to 12% by weight of mizolastine, a fatty matrix, an organic acid and a coating.
9. A coated sustained release tablet according to claim 8 , which has a dissolution profile which is pH independent.
10. A coated sustained release tablet, consisting essentially of mizolastine, a fatty matrix, an organic acid, and a coating, the coated tablet having a dissolution profile which is pH independent, the organic acid being a member selected from the group consisting of maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acid in the form of a racemate or an isomer.
11. A pharmaceutical dosage form which comprises a coated tablet having a sustained-release core, said core comprising a combination of:
a) mizolastine as active principle;
b) a fatty matrix; and
c) an organic acid;
wherein the coated tablet has a dissolution profile wherein about 50% of the mizolastine is dissolved in 1 hour, and 100% of the mizolastine is dissolved in 3 to 5 hours.
12. A sustained-release pharmaceutical dosage form according to claim 11 wherein the weight ratio of the mizolastine to the organic acid is between 0.3 and 1.
13. A sustained-release pharmaceutical dosage form according to claim 11 wherein the fatty matrix is a member selected from the group consisting of hydrogenated castor oil, a hydrogenated lecithin, a long-chain fatty acid and a triglyceride esterified with one, two or three medium-chain fatty acids.
14. A sustained-release pharmaceutical dosage form according to claim 11 wherein the organic acid is a member selected from the group consisting of maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acid in the form of a racemate or an isomer.
15. A sustained-release pharmaceutical dosage form according to claim 11 wherein the organic acid is L-tartaric acid.
16. A sustained-release pharmaceutical dosage form according to claim 15 wherein the ratio between the mizolastine and the L-tartaric acid is 0.5.
17. A sustained-release pharmaceutical dosage form according to claim 9 which contains from 1 to 25 mg of mizolastine.
18. A coated sustained-release tablet having:
a) a core comprising mizolastine, a fatty matrix and an organic acid;
b) a dissolution profile which is pH independent;
c) an in vivo mizolastine release which prevents any plasma peak; and
d) a mizolastine bioavailability which is not decreased relative to that of an immediate release formulation;
wherein the mizolastine comprises from 0.5% to 12% by weight of the tablet.
19. A sustained-release tablet of claim 18 wherein the dissolution profile is one in which about 30 to 70% of the mizolastine is dissolved in 1 hour and 100% of the mizolastine is dissolved in 3 to 5 hours.
20. A sustained-release tablet of claim 18 wherein the weight ratio between the mizolastine and the organic acid is between 0.3 and 1.
21. A sustained-release tablet of claim 18 wherein the fatty matrix is a member selected from the group consisting of hydrogenated castor oil, a hydrogenated lecithin, a long-chain fatty acid and a triglyceride esterified with one, two or three medium-chain fatty acids.
22. A sustained-release tablet of claim 18 wherein the organic acid is a member selected from the group consisting of maleic, tartaric, malic, fumaric, lactic, citric, adipic and succinic acid in the form of a racemate or an isomer.
23. A sustained-release tablet of claim 18 wherein the organic acid is L-tartaric acid.
24. A sustained-release tablet of claim 23 wherein the ratio between the mizolastine and the L-tartaric acid is 0.5.
25. A sustained-release tablet of claim 18 wherein the core contains from 1 to 25 mg of mizolastine.
26. A sustained-release tablet of claim 18 wherein the organic acid has a pK of 2 or more.
27. A coated sustained-release tablet comprising from 1 to 25 mg of mizolastine, a fatty matrix and L-tartaric acid, and the weight ratio of the mizolastine and the L-tartaric acid is between 0.3 and 1.
28. A coated sustained-release tablet of claim 27 , wherein the ratio between the mizolastine and the L-tartaric acid is 0.5.
29. A coated sustained-release tablet of claim 28 , wherein the fatty matrix is hydrogenated castor oil.
30. A coated sustained-release tablet of claim 29 , wherein the tablet has a dissolution profile which is independent of pH and is one in which about 50% of the mizolastine is dissolved in 1 hour and 100% of the mizolastine is dissolved in 3 to 5 hours.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/027,680 US20050202089A1 (en) | 1996-03-04 | 2005-01-03 | Sustained-release pharmaceutical formulations containing mizolastine |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9602662A FR2745500B1 (en) | 1996-03-04 | 1996-03-04 | SUSTAINED RELEASE PHARMACEUTICAL FORMULATIONS CONTAINING MIZOLASTINE |
FR9602662 | 1996-03-04 | ||
PCT/FR1997/000355 WO1997032584A1 (en) | 1996-03-04 | 1997-02-28 | Slow-release pharmaceutical formulations containing mizolastin |
US09/125,810 US6165507A (en) | 1996-03-04 | 1997-02-28 | Slow-release pharmaceutical formulations containing mizolastine |
US60505400A | 2000-06-28 | 2000-06-28 | |
US11/027,680 US20050202089A1 (en) | 1996-03-04 | 2005-01-03 | Sustained-release pharmaceutical formulations containing mizolastine |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US60505400A Continuation | 1996-03-04 | 2000-06-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050202089A1 true US20050202089A1 (en) | 2005-09-15 |
Family
ID=9489799
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/125,810 Expired - Lifetime US6165507A (en) | 1996-03-04 | 1997-02-28 | Slow-release pharmaceutical formulations containing mizolastine |
US11/027,680 Abandoned US20050202089A1 (en) | 1996-03-04 | 2005-01-03 | Sustained-release pharmaceutical formulations containing mizolastine |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/125,810 Expired - Lifetime US6165507A (en) | 1996-03-04 | 1997-02-28 | Slow-release pharmaceutical formulations containing mizolastine |
Country Status (35)
Country | Link |
---|---|
US (2) | US6165507A (en) |
EP (1) | EP0906101B1 (en) |
JP (2) | JP2000512617A (en) |
KR (1) | KR100369888B1 (en) |
CN (1) | CN1112929C (en) |
AR (1) | AR006082A1 (en) |
AT (1) | ATE219365T1 (en) |
AU (1) | AU725494B2 (en) |
BG (1) | BG63451B1 (en) |
BR (1) | BR9707827A (en) |
CA (1) | CA2247405C (en) |
CO (1) | CO4780020A1 (en) |
CY (1) | CY2293B1 (en) |
CZ (1) | CZ291418B6 (en) |
DE (1) | DE69713505T2 (en) |
DK (1) | DK0906101T3 (en) |
EE (1) | EE03511B1 (en) |
ES (1) | ES2177942T3 (en) |
FR (1) | FR2745500B1 (en) |
HK (1) | HK1017999A1 (en) |
HU (1) | HU227472B1 (en) |
IL (1) | IL126050A (en) |
IN (1) | IN187739B (en) |
NO (1) | NO315841B1 (en) |
NZ (1) | NZ331947A (en) |
OA (1) | OA10854A (en) |
PL (1) | PL189813B1 (en) |
PT (1) | PT906101E (en) |
RU (1) | RU2173997C2 (en) |
SK (1) | SK282112B6 (en) |
TR (1) | TR199801574T2 (en) |
TW (1) | TW491711B (en) |
UA (1) | UA49004C2 (en) |
WO (1) | WO1997032584A1 (en) |
ZA (1) | ZA971830B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US9186411B2 (en) | 2008-07-28 | 2015-11-17 | Takeda Pharmaceutical Company Limited | Pharmaceutical composition |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2002087960A (en) * | 2000-07-14 | 2002-03-27 | Toyama Chem Co Ltd | Sustained release tablet |
KR100713234B1 (en) * | 2000-10-02 | 2007-05-02 | 유에스브이 리미티드 | Sustained release pharmaceutical compositions containing metformin and method of its production |
US7052706B2 (en) | 2001-06-08 | 2006-05-30 | Nostrum Pharmaceuticals, Inc. | Control release formulation containing a hydrophobic material as the sustained release agent |
US20030181488A1 (en) * | 2002-03-07 | 2003-09-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof |
BR0318167A (en) * | 2003-03-04 | 2006-02-21 | Nostrum Pharmaceuticals Inc | controlled release formulation containing a hydrophobic material as the controlled release agent |
DE10337697A1 (en) * | 2003-08-16 | 2005-03-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Tablet containing 3 - [(2 - {[4- (hexyloxycarbonylamino-iminomethyl) -phenyl-amino] -methyl} -1-methyl-1H-benzimidazole-5-carbonyl) -pyridin-2-yl-amino] - propionic acid ethyl ester or its salts |
JP5744412B2 (en) * | 2010-03-26 | 2015-07-08 | テバ製薬株式会社 | Furosemide formulation |
US20140179712A1 (en) | 2012-12-21 | 2014-06-26 | Astrazeneca Ab | Pharmaceutical formulation of n-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2h-pyrazol-3-yl]-4-[(3r,5s)-3,5-dimethylpiperazin-1-yl]benzamide |
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US4364945A (en) * | 1979-12-13 | 1982-12-21 | Whittle Barry J | Nasal composition for relieving nasal distress |
US4421736A (en) * | 1982-05-20 | 1983-12-20 | Merrel Dow Pharmaceuticals Inc. | Sustained release diethylpropion compositions |
US4590062A (en) * | 1984-04-16 | 1986-05-20 | Tech Trade Corp. | Dry direct compression compositions for controlled release dosage forms |
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FR2587029B1 (en) * | 1985-09-11 | 1987-10-30 | Synthelabo | BENZIMIDAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
JPH0776172B2 (en) * | 1986-04-16 | 1995-08-16 | 藤沢薬品工業株式会社 | Matrice locks |
JPS62283926A (en) * | 1986-06-02 | 1987-12-09 | Nippon Chemiphar Co Ltd | Long-acting composition of nicardipine hydrochloride |
DE3812799A1 (en) * | 1988-04-16 | 1989-10-26 | Sanol Arznei Schwarz Gmbh | ORGANIC PREPARATION FOR THE PURPOSES OF AN ACTUATED ACTIVE INGREDIENTS AND METHOD OF PREPARING THEM |
JP3195391B2 (en) * | 1991-11-14 | 2001-08-06 | エスエス製薬株式会社 | Sustained-release trapidil tablets |
US5686105A (en) * | 1993-10-19 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
IT1264696B1 (en) * | 1993-07-09 | 1996-10-04 | Applied Pharma Res | PHARMACEUTICAL FORMS INTENDED FOR ORAL ADMINISTRATION ABLE TO RELEASE ACTIVE SUBSTANCES AT A CONTROLLED AND DIFFERENTIATED SPEED |
JPH07112932A (en) * | 1993-08-27 | 1995-05-02 | Mitsui Toatsu Chem Inc | Sustained release medicine preparation |
-
1996
- 1996-03-04 FR FR9602662A patent/FR2745500B1/en not_active Expired - Fee Related
-
1997
- 1997-02-27 IN IN358CA1997 patent/IN187739B/en unknown
- 1997-02-27 TW TW086102425A patent/TW491711B/en not_active IP Right Cessation
- 1997-02-28 CN CN97192804A patent/CN1112929C/en not_active Expired - Lifetime
- 1997-02-28 RU RU98118019/14A patent/RU2173997C2/en active
- 1997-02-28 WO PCT/FR1997/000355 patent/WO1997032584A1/en active IP Right Grant
- 1997-02-28 EP EP97907145A patent/EP0906101B1/en not_active Expired - Lifetime
- 1997-02-28 JP JP09531506A patent/JP2000512617A/en active Pending
- 1997-02-28 HU HU9902458A patent/HU227472B1/en unknown
- 1997-02-28 BR BR9707827A patent/BR9707827A/en not_active IP Right Cessation
- 1997-02-28 PL PL97328763A patent/PL189813B1/en unknown
- 1997-02-28 IL IL12605097A patent/IL126050A/en not_active IP Right Cessation
- 1997-02-28 TR TR1998/01574T patent/TR199801574T2/en unknown
- 1997-02-28 CO CO97010841A patent/CO4780020A1/en unknown
- 1997-02-28 CZ CZ19982791A patent/CZ291418B6/en not_active IP Right Cessation
- 1997-02-28 SK SK1210-98A patent/SK282112B6/en not_active IP Right Cessation
- 1997-02-28 CA CA002247405A patent/CA2247405C/en not_active Expired - Lifetime
- 1997-02-28 AT AT97907145T patent/ATE219365T1/en active
- 1997-02-28 DK DK97907145T patent/DK0906101T3/en active
- 1997-02-28 US US09/125,810 patent/US6165507A/en not_active Expired - Lifetime
- 1997-02-28 KR KR10-1998-0706802A patent/KR100369888B1/en active IP Right Grant
- 1997-02-28 UA UA98084447A patent/UA49004C2/en unknown
- 1997-02-28 ES ES97907145T patent/ES2177942T3/en not_active Expired - Lifetime
- 1997-02-28 PT PT97907145T patent/PT906101E/en unknown
- 1997-02-28 DE DE69713505T patent/DE69713505T2/en not_active Expired - Lifetime
- 1997-02-28 EE EE9800275A patent/EE03511B1/en unknown
- 1997-02-28 AU AU19300/97A patent/AU725494B2/en not_active Expired
- 1997-03-03 ZA ZA9701830A patent/ZA971830B/en unknown
- 1997-03-03 AR ARP970100839A patent/AR006082A1/en active IP Right Grant
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1998
- 1998-08-12 BG BG102692A patent/BG63451B1/en unknown
- 1998-09-02 NO NO19984035A patent/NO315841B1/en not_active IP Right Cessation
- 1998-09-04 OA OA9800160A patent/OA10854A/en unknown
- 1998-09-18 NZ NZ331947A patent/NZ331947A/en not_active IP Right Cessation
-
1999
- 1999-06-30 HK HK99102759A patent/HK1017999A1/en not_active IP Right Cessation
-
2002
- 2002-08-26 CY CY0200052A patent/CY2293B1/en unknown
-
2005
- 2005-01-03 US US11/027,680 patent/US20050202089A1/en not_active Abandoned
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2007
- 2007-03-05 JP JP2007054262A patent/JP2007182451A/en active Pending
Patent Citations (3)
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US4364945A (en) * | 1979-12-13 | 1982-12-21 | Whittle Barry J | Nasal composition for relieving nasal distress |
US4421736A (en) * | 1982-05-20 | 1983-12-20 | Merrel Dow Pharmaceuticals Inc. | Sustained release diethylpropion compositions |
US4590062A (en) * | 1984-04-16 | 1986-05-20 | Tech Trade Corp. | Dry direct compression compositions for controlled release dosage forms |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9186411B2 (en) | 2008-07-28 | 2015-11-17 | Takeda Pharmaceutical Company Limited | Pharmaceutical composition |
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