AU2002212290A1 - New pharmaceutical compositions containing epinastine and pseudoephedrine - Google Patents
New pharmaceutical compositions containing epinastine and pseudoephedrineInfo
- Publication number
- AU2002212290A1 AU2002212290A1 AU2002212290A AU2002212290A AU2002212290A1 AU 2002212290 A1 AU2002212290 A1 AU 2002212290A1 AU 2002212290 A AU2002212290 A AU 2002212290A AU 2002212290 A AU2002212290 A AU 2002212290A AU 2002212290 A1 AU2002212290 A1 AU 2002212290A1
- Authority
- AU
- Australia
- Prior art keywords
- pseudoephedrine
- effective amount
- epinastine
- pharmaceutically acceptable
- layer
- 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.)
- Granted
Links
Description
New pharmaceutical compositions containing epinastine and pseudoephedrine
Background of the invention The present invention relates to novel oral pharmaceutical compositions comprising as pharmaceutically active compounds a combination of an antihistaminic-effective amount of epinastine or a pharmaceutically acceptable salt thereof and of a decongestant-effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof and further comprising suitable pharmaceutically acceptable carriers or excipients. The invention further relates to methods for the preparation these compositions and methods of using them in the treatment of allergic diseases and/or disorders.
Description of the invention The present invention provides for novel oral pharmaceutical compositions comprising as pharmaceutically active compounds a combination of an antihistaminic-effective amount of epinastine or a pharmaceutically acceptable salt thereof and of a decongestant-effective amount of pseudoephedrine or a pharmaceutically accptable salt thereof and further comprising pharmaceutically acceptable carriers or excipients under the proviso that the composition does not contain a leukotriene antagonist.
As an additional active compound the compositions according to the invention may optionally contain one or several compounds selected from the group consiting of mucolitic and analgesic-antipyretic compounds and vitamines. Preferred mucolitic ingredients are selected from bromhexine and ambroxol. Preferred analgesic- antipyretic compounds are selected from paracetamol and-obuprofen. Preferred vitamines are selected from vitamine B2, B6 and C.
The pharmaceutical compositions according to the invention are useful for the treatment of allergic rhinitis, allergic congestion of the Eustachian tubes and / or other diseases from allergic origin deserving the administration of antihistamine and decongestant drugs. Furthermore the compositions according to the invention are useful in the treatment of for instance common cold and in the symptomatic relief associated with cough, cold and flu symptoms. The use of the pharmaceutical compositions according to the invention for the treatment of allergic rhinitis, allergic
congestion of the Eustachian tubes and / or other diseases from allergic origin deserving the administration of antihistamine and decongestant drugs is preferred.
In a preferred embodiment the pharmaceutical composition according to the invention contains as the active ingredients only an antihistaminic-effective amount of epinastine or a pharmaceutically acceptable salt thereof and a decongestant- effective amount of pseudoephedrine or a pharmaceutically accptable salt thereof
In a preferred embodiment the present invention relates to an oral pharmaceutical composition, preferably a bilayer tablet, providing for a sustained release of the decongestant effective amount of pseudoephedrine and an immediate release of an antihistaminic effective amount of epinastine.
Particularily preferred according to the invention is a bilayer tablet wherein a first layer A, providing for the sustained release of pseudoephedrine, comprises a decongestant effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof and wherein a second layer B, providing for the. immediate release of epinastine, comprises an antihistaminic effective amount of epinastine or a pharmaceutically acceptable salt thereof. The bilayer tablet according to the invention may additionally contain a tablet coating C consisting of pharmaceutically acceptable excipients which mask the bitter taste of one of the active compounds.
In a preferred embodiment of the invention layer A of the bilayer tablet according to the invention comprises a decongestant effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof in a matrix of a swellable hydrophilic polymer which provides a sustained release profile in a period of 3 to 24, preferably 6 to 18, most preferably about 12 hours.
According to the invention the term pharmaceutically acceptable salts stands for acid addition salts of the active compounds pseudoephedrine and epinastine. These acid addition salts can be formed with anorganic acids like hydrochloric acid, hydrobromic acid or sulfuric acid or with organic acids as for instance oxalic acid, fumaric acid or methansulfonic acid. Epinastine is preferably used as its hydrochloric acid addition
salt. Pseudoephedrine is preferebly used as the hydrochloride or the sulfate. Within the present invention pseudoephedrine sulfate is most preferred.
The release of pseudoephedrine takes place over 3 to 24, preferably 6 to 18, most preferably about 12 hours. This bilayer tablet is designed to be preferably administered twice daily.
The concentration range of pseudoephedrine salt in the compositions according to the invention is between 5 and 240 mg/tablet, preferably 10 to 200 mg/tablet, more preferably 60 to 180 mg/tablet, preferably 80 to 140 mg/tablet, most preferably 120 mg/tablet. The concentration range of epinastine salt in the compositions according to the invention is between 2 and 20 mg/tablet, preferably 5 to 10 mg/tablet, more preferably 10 mg/tablet.
Each layer of the tablet is in contact with each other in a portion of their surface, but provides independent release profiles for both active substances mentioned before. The sustained release layer A consists of pseudoephedrine or a pharmaceutically acceptable salt thereof and a swellable hydrophilic polymer . Typical swellable hydrophilic polymers include cellulosic ethers such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, carboxymethyicellulose and carboxyethylcellulose or mixtures thereof. The use of hydroxypropylmethylcellulose (HPMC) is preferred. Particularly useful are the HPMC polymers HPMC USP2910 and USP2208 like for instance Methocel E5.. E4M, E15M, K15M, and K100M supplied by the Dow Chemical Company. In the aformentioned abbreviations the designation "E" refers to USP2910 whereas "K" refers to USP2208. The number designation refers to the viscosity in a 2% aqueous solution (e.g. 5 designates a viscosity of 5 cps; 15M designates a viscosity of 15000 cps).
The excipients that could be optionally used in the sustained release layer A, are insoluble polymers, soluble or insoluble fillers, antiadherents, coloring agents, lubricants and additional binders. Typical fillers are for example lactose, microcrystalline cellulose, dibasic calcium phosphate and comstarch. Examples of antiadherents, which are used to prevent tablets from sticking to the tablet press, are
colloidal silicon dioxide and talc. Magnesium stearate, talc and stearic acid are typical lubricants. Typical binders are povidone, and cornstarch.
The immediate release matrix layer B comprises epinastine within different combinations of excipients. The excipients that could be optionally used in the immediate release layer B are insoluble polymers, soluble or insoluble fillers, antiadherents, lubricants, coloring agents.disintegrants and additional binders. Typical fillers are for example lactose, microcrystalline cellulose, dibasic calcium phosphate and cornstarch. Examples of antiadherents, which are used to prevent tablets from sticking to the tablet press, are colloidal silicon dioxide and talc. Typical disintegrants are crospovidone, sodium starch glycolate and crosscarmellose sodium. Typical coloring agents are selected from FD&C red 40 HT Aluminum lake, 2-hydroxy-1 ,r-azonaphthalene-3,6,4'-trisulfonic acid trisodium salt, erythrosine, iron oxides, 1-(4-sulpho-1-naphthylazo)-2-naphthol-6,8-disulphonic acid trisodium salt, 2',4,,5',7'-tetrabromo-4,5,6,7-tetrachloro-fluorescein disodium salt, 2,4,5,7-Tetraiodo- ι 3,6-dihydroxyxanthene-9-spiro-1 ,-(4',5',6,,7,-tetrachloro-3'H-isobenzofuran-3,one dipotassium salt, trisodium 3-carboxy-5-hydroxy-1-p-sulphophenyl-4-p- sulfophenylazopyrazole, 6-hydroxy-5-((4-sulphonphenyl)azo-2-naphthalenesulphonic acid disodium salt and optionally aluminium lakes thereof. Magnesium stearate, talc and stearic acid are typical lubricants. Typical binders are povidone, and cornstarch.
Water and ethanol are examples of volatile components which can be used in the manufacture process of both layers to granulate powders. These volatile components are removed during processing and therefore do not appear in the finished product.
The tablet coating is optional since the presence of it does not modifies significantly the release rates of the active substances present in the core layers. The presence of the coating is preferred because it masks the bitter taste of one of the active substances and enhances the properties of dosage form. Because of that a lot different coatings with different polymers, and plasticizers and other excipients could be used with the condition of not modifying significantly the release profile of the active substances present in the core tablet. A typical coating comprises a polymer such as hydroxypropylmethylcellulose and a plasticizer such as polyethylene glycol.
Optional excipients could be added to the coating like antifoaming agents and opacifying. Example of an antifoaming agent is silicone. Examples of opacifying agents are Titanium dioxide, talc and aluminum lake dyes.
The invention will be further described by the following examples. These examples disclose certain preferred embodiments of the invention. The methods of manufacturing the compositions according to the invention like for instance granulation, tablet compression, tablet coating etc. are well known to the person skilled in the art. Those skilled in the art will appreciate that various changes, modifications and substitutions can be made therein without departing from the spirit of the invention. Accordingly, it is intended that the invention be not limited to the following explicitly disclosed examples.
Example N°1 - Composition Core
A. First layer
B. Second layer
C. Coatin
* PR means Premium grade and CR means Controlled Released grade.
Method of Manufacture A. First laver:
A1. Dissolve povidone in a hydroalcoholic mixture;
A2. Blend pseudoephedrine sulfate, a portion of the microcrystalline cellulose, lactose and Methocel K15M for 5-30 minutes in a suitable mixer.
A3. Use alcoholic or hydroalcoholic solution prepared previously in step A1. to granulate the powder mix. A4. Dry and mill the pseudoephedrine sulfate granulation from step A3, using . suitable size screen. A5. Blend the screened pseudoephedrine sulfate granulation with a portion of the microcrystalline cellulose and colloidal silicon dioxide for 3-15 minutes. A6. Add magnesium stearate and blend for 3-15 minutes.
B Second laver: B1. Pass through a suitable screen Epinastine HCL, Allura red AC (FD & C red 40 HT) aluminum lake and microcrystalline cellulose. Blend for 5-30 minutes in a suitable mixer. B2. Add lactose and povidone. Blend for 60 minutes 15-120 minutes in a suitable mixer. B3. Add magnesium stearate. Btend for 3-20 minutes in a suitable mixer.
C. Compression:
Compress A and B into a suitable bilayer tableting machine in suitable size tablets.
D. Coating
D1. Dissolve Methocel E5 and Polyethylene Glycol in suitable amount of water. D2. Dissolve silicone antifoam in suitable amount of isopropilic alcohol.
D3. Add 2. to 1. and mix.
D4. Coat tablets with the Methocel E5 /Polyethylene glycol solution from step D3. in a suitable coater.
Example N° 2 - Composition
Core
A. First layer
B. Second
C. Coating
* PR means Premium grade and CR means Controlled Released grade.
Method of Manufacture
A. First laver:
A1. Blend pseudoephedrine sulfate, microcrystalline cellulose, lactose, colloidal silicon dioxide and HPMC K15M for 5-30 minutes in a suitable mixer.
A2. Add magnesium stearate and blend for 3-15 minutes.
B. Second laver:
B1. Pass through a suitable screen Epinastine HCI, and microcrystalline cellulose. Blend for 5-30 minutes in a suitable mixer.
B2. Add lactose. Blend for 60 minutes 15-120 minutes in a suitable mixer.
B3. Add magnesium stearate. Blend for 3-20 minutes in a suitable mixer.
C. Compression: Compress A and B into a suitable bilayer tableting machine in suitable size tablets.
D. Coating
D1. Dissolve Methocel E5 and Polyethylene Glycol in suitable amount of water. D2. Add Titanium Dioxide and Talc in suitable amount of water and mix D3. Add 2. to 1. And mix.
D4. Coat tablets with the Methocel E5 /Polyethylene glycol solution from step D3. in a suitable coater.
Example N° 3 Core
A. First layer
* PR means Premium grade and CR means Controlled Released grade.
Second layer and coating are identical to example 2; the manufacture method was conducted analogously to the method outlined in example 2;
Example N° 4
Core
A. First layer
PR means Premium grade and CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 5
Core
A. First layer
CR means Controlled Released grade.
Second layer and coating are identical to example 1; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 6 Core A. First layer
' CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 7
Core
A. First layer
* CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 8 Core
A. First layer
* CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 9
Core
A. First layer
CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 10 Core
A. First layer
* CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 11
Core
A. First layer
CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 12 Core
A. First layer
CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Example N° 13
Core
A. First layer
* CR means Controlled Released grade.
Second layer and coating are identical to example 1 ; the manufacture method was conducted analogously to the method outlined in example 1 ;
Claims (1)
- Claims1 ) Oral pharmaceutical compositions comprising as pharmaceutically active compounds a combination of an antihistaminic-effective amount of epinastine or a pharmaceutically acceptable salt thereof and of a decongestant-effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof and further comprising pharmaceutically acceptable carriers or excipients under the proviso that the composition does not contain a leukotriene antagonist.2) Oral pharmaceutical composition according to claim 1 , characterized in that it contains as the active ingredients only an antihistaminic-effective amount of epinastine or a pharmaceutically acceptable salt thereof and a decongestant- effective amount of pseudoephedrine or a pharmaceutically accptable salt thereof.3) Oral pharmaceutical composition according to claim 1 or 2, providing for a sustained release of the decongestant effective amount of pseudoephedrine and an immediate release of an antihistaminic effective amount of epinastine.4) Oral pharmaceutical composition according to claims 1 , 2 or 3, characterized in that it represents a bilayer tablet.5) Bilayer tablet according to claim 4, wherein a first layer A, providing for the sustained release of pseudoephedrine, comprises a decongestant effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof and wherein a second layer B, providing for the immediate release of epinastine, comprises an antihistaminic effective amount of epinastine or a pharmaceutically acceptable salt thereof.6) Bilayer tablet according to claim 5, characterized in that it additionally contains a tablet coating C consisting of pharmaceutically acceptable excipients. 7) Bilayer tablet according to claim 4, 5 or 6, characterized in that layer A comprises a decongestant effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof in a matrix of a swellable hydrophilic polymer. 58) Bilayer tablet according to claim 4, 5, 6 or 7, characterized in that the concentration range of pseudoephedrine salt is 5 and 240 mg/tablet and the concentration range of epinastine salt in the compositions according to the invention is between 2 and 20 mg/tablet.109) Bilayer tablet according to one of claims 4 to 8, characterized in that layer A comprises 120 mg pseudoephedrine sulfate and layer B comprises 10 mg epinastine-HCI.15 10) Use of a pharmaceutical composition according to one of claims 1 to 9 for the treatment of allergic rhinitis, allergic congestion of the Eustachian tubes and / or other diseases from allergic origin deserving the administration of antihistamine and decongestant drugs, in the treatment of for instance common cold and in the symptomatic relief associated with cough, cold and flu symptoms. 011 ) Use of a pharmaceutical composition according to claim 10 for the treatment of allergic rhinitis, allergic congestion of the Eustachian tubes and / or other diseases from allergic origin deserving the administration of antihistamine and decongestant drugs, preferably of allergic rhinitis. 5
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00121828.8 | 2000-10-06 | ||
| EP00121828 | 2000-10-06 | ||
| PCT/EP2001/011229 WO2002028373A1 (en) | 2000-10-06 | 2001-09-28 | New pharmaceutical compositions containing epinastine and pseudoephedrine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002212290A1 true AU2002212290A1 (en) | 2002-06-27 |
| AU2002212290B2 AU2002212290B2 (en) | 2006-08-03 |
Family
ID=8170029
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002212290A Ceased AU2002212290B2 (en) | 2000-10-06 | 2001-09-28 | New pharmaceutical compositions containing epinastine and pseudoephedrine |
| AU1229002A Pending AU1229002A (en) | 2000-10-06 | 2001-09-28 | New pharmaceutical compositions containing epinastine and pseudoephedrine |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU1229002A Pending AU1229002A (en) | 2000-10-06 | 2001-09-28 | New pharmaceutical compositions containing epinastine and pseudoephedrine |
Country Status (32)
| Country | Link |
|---|---|
| EP (1) | EP1326586B1 (en) |
| JP (1) | JP2004521864A (en) |
| KR (1) | KR20030036894A (en) |
| CN (1) | CN1291715C (en) |
| AR (2) | AR032479A1 (en) |
| AT (1) | ATE424813T1 (en) |
| AU (2) | AU2002212290B2 (en) |
| BG (1) | BG107686A (en) |
| BR (1) | BR0114339A (en) |
| CA (1) | CA2423288C (en) |
| CZ (1) | CZ2003945A3 (en) |
| DE (1) | DE60137952D1 (en) |
| EA (1) | EA007288B1 (en) |
| EC (1) | ECSP034513A (en) |
| EE (1) | EE200300138A (en) |
| ES (1) | ES2323570T3 (en) |
| HK (1) | HK1062196A1 (en) |
| HR (1) | HRP20030259A2 (en) |
| HU (1) | HUP0300970A3 (en) |
| IL (1) | IL154884A0 (en) |
| ME (1) | MEP39708A (en) |
| MX (1) | MXPA03002900A (en) |
| MY (1) | MY131159A (en) |
| NO (1) | NO20031537L (en) |
| NZ (1) | NZ525653A (en) |
| PE (1) | PE20020324A1 (en) |
| PL (1) | PL366123A1 (en) |
| SK (1) | SK4052003A3 (en) |
| UA (1) | UA75896C2 (en) |
| WO (1) | WO2002028373A1 (en) |
| YU (1) | YU24603A (en) |
| ZA (1) | ZA200302079B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0210534A (en) * | 2001-06-20 | 2004-06-22 | Schering Corp | Antihistamines for the treatment of nasal congestion and nasal obstruction |
| JP4549618B2 (en) * | 2001-11-22 | 2010-09-22 | 第一三共ヘルスケア株式会社 | Composition for rhinitis |
| CA2494065A1 (en) * | 2002-08-02 | 2004-02-19 | Boehringer Ingelheim International Gmbh | Pharmaceutical formulations comprising combinations of epinastine, pseudoephedrine and methylephedrine |
| JP5021155B2 (en) * | 2003-08-01 | 2012-09-05 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Pharmaceutical composition for the treatment of skin diseases comprising a combination of epinastine and one or more further anti-H1-histamines |
| US20070196396A1 (en) * | 2004-02-11 | 2007-08-23 | Rubicon Research Private Limited | Controlled release pharmaceutical compositions with improved bioavailability |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0903151A1 (en) * | 1997-09-22 | 1999-03-24 | ASTA Medica Aktiengesellschaft | Use of combinations comprising non-sedating antihistamines and alpha-adrenergic drugs for the topical treatment of rhinitis/conjunctivitis and cold, cold-like and/or flu symptoms |
| ATE331522T1 (en) * | 1997-12-23 | 2006-07-15 | Schering Corp | COMPOSITION FOR THE TREATMENT OF RESPIRATORY AND SKIN DISEASES WITH AT LEAST ONE LEUCOTRIEN ANTAGONIST AND AT LEAST ONE ANTHISTAMINIC |
| CN1329490A (en) * | 1998-10-09 | 2002-01-02 | 先灵公司 | Composition and method for treating allergic diseases |
| US6613357B2 (en) * | 2000-01-13 | 2003-09-02 | Osmotica Corp. | Osmotic device containing pseudoephedrine and an H1 antagonist |
-
2001
- 2001-09-04 PE PE2001000883A patent/PE20020324A1/en not_active Application Discontinuation
- 2001-09-28 CN CNB018169376A patent/CN1291715C/en not_active Expired - Lifetime
- 2001-09-28 HU HU0300970A patent/HUP0300970A3/en unknown
- 2001-09-28 KR KR10-2003-7004846A patent/KR20030036894A/en not_active Application Discontinuation
- 2001-09-28 AU AU2002212290A patent/AU2002212290B2/en not_active Ceased
- 2001-09-28 IL IL15488401A patent/IL154884A0/en unknown
- 2001-09-28 ME MEP-397/08A patent/MEP39708A/en unknown
- 2001-09-28 EE EEP200300138A patent/EE200300138A/en unknown
- 2001-09-28 JP JP2002531999A patent/JP2004521864A/en active Pending
- 2001-09-28 SK SK405-2003A patent/SK4052003A3/en unknown
- 2001-09-28 CA CA002423288A patent/CA2423288C/en not_active Expired - Lifetime
- 2001-09-28 EP EP01980449A patent/EP1326586B1/en not_active Expired - Lifetime
- 2001-09-28 MX MXPA03002900A patent/MXPA03002900A/en active IP Right Grant
- 2001-09-28 AT AT01980449T patent/ATE424813T1/en active
- 2001-09-28 PL PL01366123A patent/PL366123A1/en unknown
- 2001-09-28 CZ CZ2003945A patent/CZ2003945A3/en unknown
- 2001-09-28 NZ NZ525653A patent/NZ525653A/en unknown
- 2001-09-28 WO PCT/EP2001/011229 patent/WO2002028373A1/en active Application Filing
- 2001-09-28 EA EA200300430A patent/EA007288B1/en not_active IP Right Cessation
- 2001-09-28 BR BR0114339-5A patent/BR0114339A/en not_active Application Discontinuation
- 2001-09-28 ES ES01980449T patent/ES2323570T3/en not_active Expired - Lifetime
- 2001-09-28 UA UA2003054060A patent/UA75896C2/en unknown
- 2001-09-28 AU AU1229002A patent/AU1229002A/en active Pending
- 2001-09-28 DE DE60137952T patent/DE60137952D1/en not_active Expired - Lifetime
- 2001-09-28 YU YU24603A patent/YU24603A/en unknown
- 2001-10-04 MY MYPI20014635A patent/MY131159A/en unknown
- 2001-10-05 AR ARP010104692A patent/AR032479A1/en not_active Application Discontinuation
-
2003
- 2003-03-13 EC EC2003004513A patent/ECSP034513A/en unknown
- 2003-03-14 ZA ZA200302079A patent/ZA200302079B/en unknown
- 2003-03-28 BG BG107686A patent/BG107686A/en unknown
- 2003-04-04 NO NO20031537A patent/NO20031537L/en not_active Application Discontinuation
- 2003-04-04 HR HR20030259A patent/HRP20030259A2/en not_active Application Discontinuation
-
2004
- 2004-06-09 HK HK04104141A patent/HK1062196A1/en not_active IP Right Cessation
-
2012
- 2012-07-19 AR ARP120102612A patent/AR087240A2/en unknown
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