EP2134325A2 - Stable solid dosage forms of an antidepressant - Google Patents

Stable solid dosage forms of an antidepressant

Info

Publication number
EP2134325A2
EP2134325A2 EP08709891A EP08709891A EP2134325A2 EP 2134325 A2 EP2134325 A2 EP 2134325A2 EP 08709891 A EP08709891 A EP 08709891A EP 08709891 A EP08709891 A EP 08709891A EP 2134325 A2 EP2134325 A2 EP 2134325A2
Authority
EP
European Patent Office
Prior art keywords
dosage form
escitalopram
starch
stabilizer
sodium
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.)
Withdrawn
Application number
EP08709891A
Other languages
German (de)
French (fr)
Inventor
Krishna Murthy Bhavanasi
Venkata Ram Mohan Rao Visinigiri
Manoj Kanti Saha
Nagaprasad Vishnubhotla
Sivakumaran Meenakshisunderam
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aurobindo Pharma Ltd
Original Assignee
Aurobindo Pharma Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Aurobindo Pharma Ltd filed Critical Aurobindo Pharma Ltd
Publication of EP2134325A2 publication Critical patent/EP2134325A2/en
Withdrawn legal-status Critical Current

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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • 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
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a stable solid dosage form comprising an anti-depressant. More particularly, the present invention relates to stable solid dosage form of escitalopram or its salts.
  • the present invention also relates to a process for the preparation of stable solid dosage form of escitalopram or its salts.
  • Citalopram is a selective, centrally active serotonin reuptake inhibitor. Citalopram hydrobromide was first disclosed in US 4, 136, 193. This patent also describes the manufacture of tablets containing salts of citalopram.
  • Citalopram hydrobromide has been approved by USFDA in 1998. Subsequent to this, the S-enantiomer of citalopram (escitalopram) was shown to have better activity profile and has been approved by FDA in 2002.
  • Escitalopram is an orally administered selective serotonin reuptake inhibitor (SSRI), and is indicated for the treatment of depression.
  • Escitalopram is marketed as oxalate salt under the trade name LEXAPROTM. Chemically, Escitalopram is (+)-l-(3-dimethylaminopropyl)- l-(4-fluorophenyl)-l,3-dihydroisobenzofuran-5-carbonitrile.
  • Escitalopram oxalate was disclosed in US 4,943,590, reissued as US RE 34,712. This patent also describes the manufacture of tablets containing salts of Escitalopram.
  • Escitalopram is a poorly soluble drug and hence poses serious dissolution problems, which may affect bioavailability.
  • Bioavailability can also be affected by a number of factors such as the amounts and types of adjuvants used, the manufacturing process, compression forces (in tablet manufacturing), the surface area available for dissolution etc.
  • the escitalopram oxalate product prepared by crystallization from acetone as outlined in US 4,943,590 has a very small particle size around 2- 20 microns resulting in poor flow properties.
  • US 2005/0196453 discloses crystalline particles of escitalopram oxalate, characterized in that the ratio between the median particle size and the particle size at the 95% quantile is less than 0.42 and the tablets prepared by direct compression method.
  • the main objective of the present invention is to provide stable solid dosage form of escitalopram or its salts, which comply with the reference product in terms of stability, in vivo parameters like C max , t ma ⁇ and AUC and in vitro parameters like dissolution, disintegration.
  • Yet another objective of the present invention is to provide simple and efficient process for preparing stable solid dosage form of escitalopram or its salts, on a commercial scale.
  • a stable solid dosage form comprising escitalopram or its salts, stabilizer and one or more pharmaceutically acceptable excipients.
  • the salt of escitalopram used according to present invention includes oxalate, hydrobromide and hydrochloride.
  • the stabilizer used according to present invention is an antioxidant selected from the group consisting of butylated hydroxy anisole (BHA), butylated hydroxytoulene (BHT), alpha tocopherol, ascorbic acid, ascorbyl palmiate, benzoic acid, cysteine hydrochloride, isoascorbic acid, propionic acid, monothioglycerol and sodium metabisulfite and the like or mixtures thereof.
  • BHA butylated hydroxy anisole
  • BHT butylated hydroxytoulene
  • alpha tocopherol alpha tocopherol
  • ascorbic acid ascorbyl palmiate
  • benzoic acid cysteine hydrochloride
  • isoascorbic acid propionic acid
  • the amount of stabilizer(s) used in the dosage form may range from about 0.01% to about 10% w/w, and preferably from about 0.02% to about 5% w/w.
  • Escitalopram may undergo oxidation during storage thereby produces oxocitalopram.
  • the quantity of oxocitalopram may increase during long-term storage which is not acceptable.
  • Antioxidants such as BHA and BHT react with the free radicals and decrease the rate of oxidation.
  • the pharmaceutically acceptable excipients include binders, diluents, disintegrants, lubricants and/or glidants and the like.
  • the preferable stable solid dosage form according to present invention comprises about 5% to about 20% w/w of escitalopram or its salts, about 70% to about 90% w/w of diluent, about 1% to about 5% w/w of disintegrant, about 0.01% to about 5% w/w of stabilizer, about 0.1 % to about 5% w/w of glidant and about 1 % to about 5% w/w of lubricant.
  • the diluents used according to the present invention are selected from dibasic calcium phosphate, calcium carbonate, lactose, sucrose, cellulose microcrystalline. cellulose powdered, silicified microcrystalline cellulose, calcium silicate, starch, starch pregelatinized, polyols such as mannitol, sorbitol, xylitol, maltitol or combination thereof.
  • Suitable disintegrants used in accordance with the present invention are selected from croscarmellose sodium, crospovidone, carboxy methyl cellulose sodium, sodium starch glycolate, starch, pregelatinised starch and the like or combination thereof.
  • Suitable binders according to the present invention are selected from methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, gelatin, ethyl cellulose, polyvinyl alcohol, starch, pregelatinized starch, agar, tragacanth, sodium alginate and the like.
  • Suitable lubricants according to the present invention are selected from sodium lauryl sulfate, talc, magnesium stearate, sodium stearyl fumarate, stearic acid, glyceryl behenate, hydrogenated vegetable oil, zinc stearate and suitable glidants include colloidal silicon dioxide and talc.
  • the particle size of the escitalopram oxalate used according to present invention is in the range of 2 to 100 ⁇ m, preferably less than 20 ⁇ m.
  • the preferable stable solid dosage form of the present invention comprises about 5% to about 20% w/vv of escitalopram or its salts, about 70% to about 90% w/w of diluent selected from silicified microcrystalline cellulose, microcrystalline cellulose, lactose, mannitol or combination thereof, about 1% to about 5% w/w of disintegrant selected from croscarmellose sodium, crospovidone and sodium starch glycolate, about 0.01 % to about 5% w/vv of stabilizer selected from butylated hydroxy anisole, burylated hydroxytoulene and alpha tocopherol or combination thereof, about 0.1 % to about 5% w/w of glidant selected from colloidal silicon dioxide and talc or combination thereof and about 1 % to about 5% w/w of lubricant selected from magnesium stearate and sodium stearyl fumarate.
  • diluent selected from silicified microcrystalline cellulose, microcrystalline cellulose, lac
  • the solid dosage form of the present invention is in the form of tablet or gelatin capsule or processed into granules for oral suspension.
  • the tablets of the present invention include uncoated tablets, tablets coated with film forming polymers such as hydroxypropylmethylcellulose, ethyl cellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide and the like.
  • a method of treating depression comprising administering to patients in need thereof a dosage form of escitalopram or its salts of the present invention.
  • the stable solid dosage form of escitalopram or its salts may be prepared by direct compression, wet granulation or dry granulation.
  • a process for the preparation of a stable solid dosage form comprising escitalopram or its salts, stabilizer and one or more pharmaceutically acceptable excipients, which comprises the steps of: i) mixing escitalopram with one or more excipients, ii) dissolving the stabilizer in the solvent and granulating the blend obtained in step (i), iii) drying the granules obtained in step (ii), iv) mixing the granules of step (iii) with one or more pharmaceutically acceptable excipients, v) lubricating the blend of step (iv) and vi) compressing the blend of step (v) into tablets.
  • Suitable solvents used for granulation are selected from water or organic solvents such as acetone, alcohol, isopropyl alcohol dichloromethane and the like or mixture thereof.
  • Example 1 (Escitalopram oxalate tablets with stabilizers)
  • step (iii) granulated the blend obtained in step (ii) with water, (iii) the granules of step (iii) were blended with microcrystalline cellulose and colloidal silicondioxide,
  • step (iv) lubricated blend of the step (iv) with talc and magnesium stearate, (v) compressed the blend of step (iv) into tablets and (vi) tablets of step (v) were then coated with a solution / suspension of opadry in water.
  • Stability Data Tablets prepared according to examples 3-5 were stored at 40°C/75%RH. for two months and then tested by an HPLC method to determine the amount of oxocitalopram. The stability data is given in table 2.

Abstract

The present invention relates to a stable solid dosage form comprising an anti-depressant. More particularly, the present invention relates to stable solid dosage form of escitalopram or its salts. The present invention also relates to a process for the preparation of stable solid dosage form of escitalopram or its salts.

Description

STABLE SOLID DOSAGE FORMS OF AN ANTIDEPRESSANT
Field of the invention
The present invention relates to a stable solid dosage form comprising an anti-depressant. More particularly, the present invention relates to stable solid dosage form of escitalopram or its salts.
The present invention also relates to a process for the preparation of stable solid dosage form of escitalopram or its salts.
Background of the invention
Citalopram is a selective, centrally active serotonin reuptake inhibitor. Citalopram hydrobromide was first disclosed in US 4, 136, 193. This patent also describes the manufacture of tablets containing salts of citalopram.
Citalopram hydrobromide has been approved by USFDA in 1998. Subsequent to this, the S-enantiomer of citalopram (escitalopram) was shown to have better activity profile and has been approved by FDA in 2002.
Escitalopram is an orally administered selective serotonin reuptake inhibitor (SSRI), and is indicated for the treatment of depression. Escitalopram is marketed as oxalate salt under the trade name LEXAPRO™. Chemically, Escitalopram is (+)-l-(3-dimethylaminopropyl)- l-(4-fluorophenyl)-l,3-dihydroisobenzofuran-5-carbonitrile. Escitalopram oxalate was disclosed in US 4,943,590, reissued as US RE 34,712. This patent also describes the manufacture of tablets containing salts of Escitalopram. Escitalopram is a poorly soluble drug and hence poses serious dissolution problems, which may affect bioavailability. For drugs having low solubility, there is considerable evidence that the dissolution partially or completely controls the rate of absorption. Bioavailability can also be affected by a number of factors such as the amounts and types of adjuvants used, the manufacturing process, compression forces (in tablet manufacturing), the surface area available for dissolution etc.
The escitalopram oxalate product prepared by crystallization from acetone as outlined in US 4,943,590 has a very small particle size around 2- 20 microns resulting in poor flow properties.
It is disclosed in US 6,916,941 that the preparation of tablets with a reproducible composition can be prepared by direct compression when the active substance and all other dry ingredients have good flow properties. However, in many cases the particle size of the active substance is small, cohesive or has poor flow properties. To overcome these problems, the inventors of US '941 developed a crystallization process that produced escitalopram oxalate having the particle size of at least 40μm, which is useful for the manufacture of directly compressed tablets.
US 2005/0196453 discloses crystalline particles of escitalopram oxalate, characterized in that the ratio between the median particle size and the particle size at the 95% quantile is less than 0.42 and the tablets prepared by direct compression method.
In our PCT publication i.e. WO 2006/123243. we disclosed pharmaceutical dosage forms comprising escitalopram prepared by a granulation technique, wherein the particle size of the escitalopram oxalate is less than 20 μm.
The above prior art references disclose formulations of escitalopram and do not disclose long term stability issues of escitalopram. Further, the inventors of the present invention during their efforts to develop solid dosage forms of escitalopram found that during the long term storage of escitalopram, oxidation related impurities might be formed. To reduce the formation of oxidative impurities and to improve the long term stability of escitalopram, some stabilizers preferably antioxidants can be added to the formulation. Antioxidant added in small quantities to hydrocarbons that are susceptible to oxidation, inhibit or slow down the oxidative process, while being itself oxidized.
Objective of the invention
Accordingly, the main objective of the present invention is to provide stable solid dosage form of escitalopram or its salts, which comply with the reference product in terms of stability, in vivo parameters like Cmax, tma^ and AUC and in vitro parameters like dissolution, disintegration.
Yet another objective of the present invention is to provide simple and efficient process for preparing stable solid dosage form of escitalopram or its salts, on a commercial scale.
Summary of the invention
According to the main embodiment of the present invention, there is provided a stable solid dosage form comprising escitalopram or its salts, stabilizer and one or more pharmaceutically acceptable excipients. Detailed description of the invention
The salt of escitalopram used according to present invention includes oxalate, hydrobromide and hydrochloride.
The stabilizer used according to present invention is an antioxidant selected from the group consisting of butylated hydroxy anisole (BHA), butylated hydroxytoulene (BHT), alpha tocopherol, ascorbic acid, ascorbyl palmiate, benzoic acid, cysteine hydrochloride, isoascorbic acid, propionic acid, monothioglycerol and sodium metabisulfite and the like or mixtures thereof.
The amount of stabilizer(s) used in the dosage form may range from about 0.01% to about 10% w/w, and preferably from about 0.02% to about 5% w/w.
Escitalopram may undergo oxidation during storage thereby produces oxocitalopram. The quantity of oxocitalopram may increase during long-term storage which is not acceptable. Antioxidants such as BHA and BHT react with the free radicals and decrease the rate of oxidation.
In an embodiment of the present invention, the pharmaceutically acceptable excipients include binders, diluents, disintegrants, lubricants and/or glidants and the like.
In another embodiment, the preferable stable solid dosage form according to present invention comprises about 5% to about 20% w/w of escitalopram or its salts, about 70% to about 90% w/w of diluent, about 1% to about 5% w/w of disintegrant, about 0.01% to about 5% w/w of stabilizer, about 0.1 % to about 5% w/w of glidant and about 1 % to about 5% w/w of lubricant.
The diluents used according to the present invention are selected from dibasic calcium phosphate, calcium carbonate, lactose, sucrose, cellulose microcrystalline. cellulose powdered, silicified microcrystalline cellulose, calcium silicate, starch, starch pregelatinized, polyols such as mannitol, sorbitol, xylitol, maltitol or combination thereof.
Suitable disintegrants used in accordance with the present invention are selected from croscarmellose sodium, crospovidone, carboxy methyl cellulose sodium, sodium starch glycolate, starch, pregelatinised starch and the like or combination thereof.
Suitable binders according to the present invention are selected from methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, gelatin, ethyl cellulose, polyvinyl alcohol, starch, pregelatinized starch, agar, tragacanth, sodium alginate and the like. Suitable lubricants according to the present invention are selected from sodium lauryl sulfate, talc, magnesium stearate, sodium stearyl fumarate, stearic acid, glyceryl behenate, hydrogenated vegetable oil, zinc stearate and suitable glidants include colloidal silicon dioxide and talc. In yet another embodiment, the particle size of the escitalopram oxalate used according to present invention is in the range of 2 to 100 μm, preferably less than 20 μm.
In another embodiment, the preferable stable solid dosage form of the present invention comprises about 5% to about 20% w/vv of escitalopram or its salts, about 70% to about 90% w/w of diluent selected from silicified microcrystalline cellulose, microcrystalline cellulose, lactose, mannitol or combination thereof, about 1% to about 5% w/w of disintegrant selected from croscarmellose sodium, crospovidone and sodium starch glycolate, about 0.01 % to about 5% w/vv of stabilizer selected from butylated hydroxy anisole, burylated hydroxytoulene and alpha tocopherol or combination thereof, about 0.1 % to about 5% w/w of glidant selected from colloidal silicon dioxide and talc or combination thereof and about 1 % to about 5% w/w of lubricant selected from magnesium stearate and sodium stearyl fumarate.
In another embodiment, the solid dosage form of the present invention is in the form of tablet or gelatin capsule or processed into granules for oral suspension.
In yet another embodiment the tablets of the present invention, include uncoated tablets, tablets coated with film forming polymers such as hydroxypropylmethylcellulose, ethyl cellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide and the like.
In yet another embodiment, there is provided a method of treating depression comprising administering to patients in need thereof a dosage form of escitalopram or its salts of the present invention.
In another embodiment, the stable solid dosage form of escitalopram or its salts may be prepared by direct compression, wet granulation or dry granulation. In yet another embodiment, there is provided a process for the preparation of a stable solid dosage form comprising escitalopram or its salts, stabilizer and one or more pharmaceutically acceptable excipients, which comprises the steps of: i) mixing escitalopram with one or more excipients, ii) dissolving the stabilizer in the solvent and granulating the blend obtained in step (i), iii) drying the granules obtained in step (ii), iv) mixing the granules of step (iii) with one or more pharmaceutically acceptable excipients, v) lubricating the blend of step (iv) and vi) compressing the blend of step (v) into tablets.
Suitable solvents used for granulation are selected from water or organic solvents such as acetone, alcohol, isopropyl alcohol dichloromethane and the like or mixture thereof.
The following examples further exemplify the invention and are not intended to limit the scope of the invention. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.
Example 1 (Escitalopram oxalate tablets with stabilizers)
The processing steps that are involved in making film coated tablets of escitalopram oxalate disclosed above are given below: (i) escitalopram oxalate, silicified microcrystalline cellulose, colloidal silicon dioxide, half the quantity of the croscarmellose were blended, (ii) BHA and BHT were dissolved in isopropyl alcohol and added to the blend of step (i),
(iii) granulated the blend obtained in step (ii) with water, (iii) the granules of step (iii) were blended with microcrystalline cellulose and colloidal silicondioxide,
(iv) lubricated blend of the step (iv) with talc and magnesium stearate, (v) compressed the blend of step (iv) into tablets and (vi) tablets of step (v) were then coated with a solution / suspension of opadry in water.
The compositions given in examples 2-5 were prepared using similar procedure as described in example 1. Example 2
Example 3
Example 4
Example 5 (Escitalopram oxalate tablets without stabilizer)
Stability Data: Tablets prepared according to examples 3-5 were stored at 40°C/75%RH. for two months and then tested by an HPLC method to determine the amount of oxocitalopram. The stability data is given in table 2.
Table 2

Claims

We claim:
1. A stable solid dosage form comprising escitalopram or its salts, stabilizer and one or more pharmaceutically acceptable excipients.
2. The dosage form of claim 1 , wherein stabilizer is selected from butylated hydroxy anisole (BHA), butylated hydroxytoulene (BHT), alpha tocopherol, ascorbic acid, ascorbyl palmiate, benzoic acid, cysteine hydrochloride, isoascorbic acid, propionic acid, monothioglycerol and sodium metabisulfite or mixture thereof.
3. The dosage form of claim 1 , wherein the amount of stabilizer(s) is in the range from about 0.01 % to about 10% w/w, and preferably from about
0.02% to about 5% w/w.
4. The dosage form of claim 1 , the pharmaceutically acceptable excipients include diluent, binder, disintegrant, lubricant and/or glidant.
5. The dosage form of claim 4, wherein the diluent is selected from dibasic calcium phosphate, calcium carbonate, lactose, sucrose, cellulose- microcrystalline, cellulose powdered, silicified microcrystalline cellulose, calcium silicate, starch, starch pregelatinized, polyols such as mannitol, sorbitol, xylitol, maltitol or combination thereof.
6. The dosage form of claim 4, wherein the binder is selected from methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, starch, pregelatinized starch, agar, tragacanth and sodium alginate.
7. The dosage form of claim 4, wherein the disintegrant is selected from croscarmellose sodium, crospovidone. carboxymethylcellulose sodium, sodium starch glycolate, starch, pregelatinised starch or combination thereof.
8. The dosage form of claim 4, wherein the lubricant is selected from sodium lauryl sulfate, talc, magnesium stearate, sodium stearyl fumarate, stearic acid, glyceryl behenate, hydrogenated vegetable oil and zinc stearate.
9. A stable solid dosage form comprising about 5% to about 20 % w/w of escitalopram or its salts, about 70% to about 90% w/w of diluent, about 1% to about 5 % w/w of disintegrant, about 0.01% to about 5% w/w of stabilizer, about 0.1 % to about 5 % w/w of glidant and about 1 % to about 5 % w/w of lubricant.
10. A process for the preparation of a stable solid dosage form comprising escitalopram or its salts, stabilizer and one or more pharmaceutically acceptable excipients, which comprises the steps of: i) mixing escitalopram with one or more excipients, ii) dissolving the stabilizer in the solvent and granulating the blend obtained in step (i), iii) drying the granules obtained in step (ii), iv) mixing the granules of step (iii) with one or more pharmaceutically acceptable excipients. v) lubricating the blend of step (iv) and vi) compressing the blend of step (v) into tablets.
1 1. The dosage form of claim 10, wherein the solvent used for granulation is selected from water or organic solvents such as acetone, alcohol, isopropyl alcohol dichloromethane or mixture thereof.
12. A method of treating depression comprising administering to patients in need thereof a dosage form of escitalopram or its salts of claim
EP08709891A 2007-03-01 2008-02-28 Stable solid dosage forms of an antidepressant Withdrawn EP2134325A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN424CH2007 2007-03-01
PCT/IB2008/000600 WO2008104880A2 (en) 2007-03-01 2008-02-28 Stable solid dosage forms of an antidepressant

Publications (1)

Publication Number Publication Date
EP2134325A2 true EP2134325A2 (en) 2009-12-23

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Country Status (2)

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Publication number Priority date Publication date Assignee Title
CN104523638B (en) * 2014-11-28 2020-02-21 浙江华海药业股份有限公司 Tablet containing escitalopram oxalate and preparation method thereof
CN106176691A (en) * 2016-08-31 2016-12-07 齐鲁制药有限公司 A kind of molten membrane of escitalopram oxalate mouth and preparation method thereof
CN106860410A (en) * 2017-03-17 2017-06-20 万全万特制药江苏有限公司 A kind of escitalopram oxalate oral disintegrating tablet and preparation method thereof
JP6423133B1 (en) * 2017-04-10 2018-11-14 東和薬品株式会社 Escitalopram pharmaceutical composition
KR102089737B1 (en) * 2017-11-01 2020-03-16 한국화학연구원 A sustained-release injection of microspheres containing escitalopram and manufacturing method thereof

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GB8814057D0 (en) * 1988-06-14 1988-07-20 Lundbeck & Co As H New enantiomers & their isolation
US20050250838A1 (en) * 2004-05-04 2005-11-10 Challapalli Prasad V Formulation for sustained delivery
EP1901714A2 (en) * 2005-05-20 2008-03-26 Aurobindo Pharma Limited Pharmaceutical dosage forms comprising escitalopram in form of granules
TWI358407B (en) * 2005-06-22 2012-02-21 Lundbeck & Co As H Crystalline base of escitalopram and orodispersibl

Non-Patent Citations (1)

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Title
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