CN101474171B - Oral solid preparation of escitalopram oxalate and preparation method thereof - Google Patents
Oral solid preparation of escitalopram oxalate and preparation method thereof Download PDFInfo
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- CN101474171B CN101474171B CN2009100780816A CN200910078081A CN101474171B CN 101474171 B CN101474171 B CN 101474171B CN 2009100780816 A CN2009100780816 A CN 2009100780816A CN 200910078081 A CN200910078081 A CN 200910078081A CN 101474171 B CN101474171 B CN 101474171B
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Abstract
The invention discloses an oxalic acid esmolol citalopram oral solid preparation and a preparation method. The oral solid preparation comprises raw materials of: 2-40 parts by weight of oxalic acid esmolol citalopram, 5-60 parts by weight of starch, 5-200 parts by weight of microcrystalline cellulose, 5-60 parts by weight of lactose, 0.05-5 parts by weight of binding agent and 0.05-3 parts by weight of lubricant; the binding agent is one or a plurality of mixed aqueous solutions or alcoholic solutions from the group consisting of polyvinyl pyrrolidone, hydroxyethyl methylcellulose, methylcellulose, hydroxypropyl cellulose and ethyl cellulose, the concentration of the binding agent is 0.1-10.0%; and the lubricant is stearic acid, magnesium stearate, calcium stearate, talcum or superfine silica gel powder.
Description
Invention field
The present invention relates to a kind of medicine, particularly a kind of oxalic acid escitalopram oral solid formulation and preparation method thereof.
Background technology
Oxalic acid escitalopram sheet (escitalopram oxalate) is a kind of oral selective serotonin reuptake inhibitor (SSRI) that has.The oxalic acid escitalopram is the S-isomer (single isomer) of racemization citalopram (citalopram).Develop jointly by Forest Laboratories and Denmark Lundbeck.
The citalopram that Forest experiment company produces was sold with different trade name (comprising Celexa, Cipramil and Seropram) in 70 countries as a kind of antidepressant from the date of approval on July 17th, 1998.After this said firm submits the escitalopram new drug application to FDA (FDA), escitalopram is used for the treatment of depression; Be given the ratification on November 27th, 2002.
Forest experiment company shows the III clinical trial phase result of novel antidepressant escitalopram: compare with citalopram, quite the escitalopram of low dosage just obviously is better than placebo to the improvement degree of symptom.Report is found the escitalopram of 10 mg/day and the citalopram therapeutic equivalence of 40 mg/day, and in the III clinical trial phase, the significant difference between this medicine and placebo occurs more early, can occur when 1 week, and citalopram then needed for 4 weeks.The few side effects of escitalopram is in citalopram (citalopram).Escitalopram (10～20 mg/day) and citalopram (20～40 mg/day) all can be tolerated well by 1,715 major depressive disorder patient.And the common adverse reactions relevant with selectivity 5-hydroxy tryptamine cell reabsorption inhibitor (SSRI) that comprises drowsiness and defective ejaculation is not therein.Show that this kind of exploitation is significant at home.This medicine is applicable to treatment depressibility mental disorder.Domesticly do not see that as yet the research of relevant oxalic acid escitalopram new drug successfully reports.
Clinical abroad efficiency evaluation: a part is on the basis of the relevant study on the efficiency of citalopram raceme, and the oxalic acid escitalopram is its active isomer, has set up the efficiency evaluation of the most of depressions of S-citalopram treatment.Iexapro is based on more than 1100 18-65 year moderate to the curative effect and the safety clinical data of major depression male and female patient by FDA approval.In a pair of 491 major depression patients establish placebo double blind control research, the 48 all administrations that one of intersect at random: placebo, oxalic acid escitalopram 10mg every day, every day 20mg or citalopram 40mg.The result shows, takes oxalic acid escitalopram 10mg and 20mg every day and significantly improve symptom than placebo group.In addition, oxalic acid escitalopram 10mg on main curative effect with citalopram 40mg.Determine that the 1st MADRS (MADRS) of measuring terminal point shows, patient takes oxalic acid escitalopram 10mg every day or 20mg significantly improves symptom with each time point of keeping thereafter than placebo group in the 2nd week.Untoward reaction only has nauseating, insomnia, premature ejaculation, somnolence, hyperhidrosis and weak in the research.
This product compound 1988 is filed an application in Britain by Denmark Lundbeck company, and this application people files an application in Europe, the U.S. again afterwards, and wherein European patent is EP347066, and nineteen ninety-five authorizes.United States Patent (USP) is US4943590, and nineteen ninety authorizes.Through checking and verify, this chemical compound does not have patent in China; And this product is not applied for administrative protection at present.Novelty assessment report shows, the domestic report of not seeing that this medicine is succeeded in developing.
The oral solid formulation of oxalic acid escitalopram does not have report so far, every in oxalic acid escitalopram tablet only contains oxalic acid escitalopram 12.78mg, must add adjuvants such as an amount of filler, solve the uniformity of dosage units and the preparation stability of oxalic acid escitalopram.
Summary of the invention
The objective of the invention is to disclose a kind of stable oxalic acid escitalopram oral solid formulation and preparation method thereof.
The present invention seeks to be achieved through the following technical solutions:
Raw material consists of: oxalic acid escitalopram 2～40 weight portions, starch 5～60 weight portions, microcrystalline Cellulose 5～200 weight portions, lactose 5～50 weight portions, binding agent 0.05～5 weight portion, lubricant 0.05～3 weight portion.
The raw material composition is preferably:
Oxalic acid escitalopram 5～30 weight portions, starch 10～45 weight portions, microcrystalline Cellulose 10～100 weight portions, lactose 10～40 weight portions, binding agent 0.1～2 weight portion, lubricant 0.1～2 weight portion.Or oxalic acid escitalopram 13 weight portions, starch 15 weight portions, microcrystalline Cellulose 50 weight portions, lactose 25 weight portions, binding agent 0.5 weight portion, lubricant 0.2 weight portion.Or oxalic acid escitalopram 26 weight portions, starch 10 weight portions, microcrystalline Cellulose 150 weight portions, lactose 20 weight portions, binding agent 0.2 weight portion, lubricant 1 weight portion.Or oxalic acid escitalopram 6 weight portions, starch 25 weight portions, microcrystalline Cellulose 20 weight portions, lactose 15 weight portions, binding agent 0.5 weight portion, lubricant 0.1 weight portion.Binding agent of the present invention is the aqueous solution or the alcoholic solution of one or more mixing (mixed proportion) among polyvinylpyrrolidone (PVPK30), hydroxyethylmethyl-cellulose (HPMC), methylcellulose, hydroxypropyl cellulose, the ethyl cellulose, and binder concn is 0.1～10.0%; Binder concn is preferably 1.0～5.0%.Lubricant of the present invention is stearic acid, magnesium stearate, calcium stearate, Pulvis Talci or micropowder silica gel etc.
Oxalic acid escitalopram oral solid formulation of the present invention can be made regular dosage form according to a conventional method; The method preparation: the microcrystalline Cellulose of getting oxalic acid escitalopram and 1/3～2/3 amount ground 60～120 mesh sieves altogether, must grind thing altogether; Starch and remaining microcrystalline Cellulose and lactose are mixed, cross 60～120 mesh sieves, get mixture; Grind thing altogether and mixed 40～100 mesh sieves with mixture, stir, add binding agent, granulate with 12～40 mesh sieves to make soft material, put in the baking oven 40～80 ℃ dry 1-4 hour, add the lubricant adjuvant, granulate makes granule, conventional method is made capsule, tablet, granule.
The preparation method of oxalic acid escitalopram oral solid formulation of the present invention is preferably: the microcrystalline Cellulose of getting oxalic acid escitalopram and 1/2 amount ground 100 mesh sieves altogether, starch and remaining microcrystalline Cellulose and lactose are mixed, cross 100 mesh sieves, grind thing altogether and progressively increase with mixture equivalent and mixed 80 mesh sieves, stir, add binding agent and make soft material, granulate with 20 mesh sieves, put in the baking oven 60 ℃ of dryings 2 hours, reuse 20 mesh sieve granulate, add the lubricant adjuvant, make tablet.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
The experimentation that experimental example 1 medicine supplementary material of the present invention is formed
According to different accessory formulas, and carry out prescription screening as investigating index, see Table 1～2 with disintegration, friability and flowability (angle of repose), the uniformity etc.
The different prescriptions of table 1 are to the screening of adjuvant
Annotate: because the 1-4 sample size uniformity is against regulation in the table, disintegration time is longer, so do not carry out dissolution and Determination on content.
The different prescriptions of table 2 are made influence factor's test of preparation
Shown that by table 1～2 5 and 6 prescriptions are for best, the quality of the pharmaceutical preparations is stable, and every index is up to specification, and the result is best, and through influence factor's test, its outward appearance, uniformity of dosage units etc. also obviously are better than other prescription.The oral formulations composition adjuvant prescription of having confirmed the oxalic acid escitalopram is starch, microcrystalline Cellulose, lactose, lubricant etc.
A kind of stable oxalic acid escitalopram oral solid formulation of the present invention and preparation method thereof can solve problems such as the formulation content uniformity preferably, can make the every index of preparation meet officinal every requirement; Influence factor's result of the test shows that also supplementary material prescription of the present invention preferably resolves the problem of disintegrate in the formulation content uniformity, the sample placement.
Following embodiment all can realize the described effect of above-mentioned experimental example
The specific embodiment
Embodiment 1: the preparation of tablet
The oxalic acid escitalopram 12.78g and the 25g microcrystalline Cellulose that take by weighing recipe quantity ground 100 mesh sieves altogether, starch 20g and remaining 25g microcrystalline Cellulose and lactose 30g are mixed, cross 80 mesh sieves, grind thing altogether and mixed 80 mesh sieves with mixture, stir, add 5% 30 POVIDONE K 30 BP/USP
30Ethanol liquid is made soft material, granulates with 20 mesh sieves, puts in the baking oven 60 ℃ of dryings 2 hours, and reuse 20 mesh sieve granulate add adjuvant magnesium stearate 0.2g, and mixing makes granule, tabletting, promptly.
Embodiment 2: the preparation of capsule
The oxalic acid escitalopram 25.56g and the 60g microcrystalline Cellulose that take by weighing recipe quantity ground 100 mesh sieves altogether, and starch 30g and remaining microcrystalline Cellulose 50g and lactose 40g are mixed, and crossed 100 mesh sieves, grind thing altogether and mixed 60 mesh sieves with mixture, stir, add 1% hydroxyethylmethyl-cellulose alcoholic solution, make soft material, granulate, put in the baking oven 70 ℃ of dryings 1.5 hours with 18 mesh sieves, reuse 18 mesh sieve granulate, add adjuvant Pulvis Talci 0.15g, mixing makes granule, the hungry area softgel shell of packing into, promptly.
Embodiment 3: the preparation of tablet
The oxalic acid escitalopram 12.78g and the 40g microcrystalline Cellulose that take by weighing recipe quantity ground 60 mesh sieves altogether, and starch 5g and remaining 80g microcrystalline Cellulose and lactose 10g are mixed, and crossed 100 mesh sieves, grind thing altogether and mixed 100 mesh sieves with mixture, stir, add 8% methylated cellulose aqueous solution, make soft material, granulate, put in the baking oven 40 ℃ of dryings 4 hours with 40 mesh sieves, reuse 30 mesh sieve granulate, add adjuvant stearic acid 0.2g, mixing makes granule, tabletting, promptly.
Embodiment 4: the preparation of capsule
The oxalic acid escitalopram 12.78g and the 60g microcrystalline Cellulose that take by weighing recipe quantity ground 60 mesh sieves altogether, and starch 20g and remaining 20g microcrystalline Cellulose and lactose 50g are mixed, and crossed 120 mesh sieves, grind thing altogether and mixed 60 mesh sieves with mixture, stir, add 0.5% hydroxypropyl cellulose alcoholic solution, make soft material, granulate, put in the baking oven 60 ℃ of dryings 2 hours with 20 mesh sieves, reuse 20 mesh sieve granulate, add adjuvant calcium stearate 0.1g, mixing makes granule, the hungry area softgel shell of packing into, promptly.
Embodiment 5: the preparation of granule
The oxalic acid escitalopram 25.56g and the 50g microcrystalline Cellulose that take by weighing recipe quantity ground 60 mesh sieves altogether, and starch 60g and remaining microcrystalline Cellulose 80g and lactose 50g are mixed, and crossed 100 mesh sieves, grinding thing altogether progressively increases with mixture equivalent and mixed 80 mesh sieves, stir, add 3% ethyl cellulose aqueous solution, make soft material, granulate with 20 mesh sieves, put in the baking oven 80 ℃ of dryings 1 hour, reuse 20 mesh sieve granulate add adjuvant micropowder silica gel 0.5g, mixing is made granule.
Claims (7)
1. an oxalic acid escitalopram oral solid formulation is characterized in that the raw material of this oral solid formulation consists of: oxalic acid escitalopram 13 weight portions, starch 15 weight portions, microcrystalline Cellulose 50 weight portions, lactose 25 weight portions, binding agent 0.5 weight portion, lubricant 0.2 weight portion; Described binding agent is one or more mixed aqueous solutions or the alcoholic solution among polyvinylpyrrolidone, hydroxyethylmethyl-cellulose, methylcellulose, hydroxypropyl cellulose, the ethyl cellulose, and binder concn is 0.1～10.0%; Described lubricant is stearic acid, magnesium stearate, calcium stearate, Pulvis Talci or micropowder silica gel.
2. oral solid formulation as claimed in claim 1, binder concn was 1.0～5.0% during the raw material that it is characterized in that this oral solid formulation was formed.
3. oral solid formulation as claimed in claim 1 or 2 is characterized in that this oral solid formulation makes regular dosage form according to a conventional method.
4. the preparation method of oral solid formulation as claimed in claim 1 or 2 is characterized in that this method is: the microcrystalline Cellulose of getting oxalic acid escitalopram and 1/3～2/3 amount ground 60～120 mesh sieves altogether, must grind thing altogether; Starch and remaining microcrystalline Cellulose, lactose are mixed, cross 60～120 mesh sieves, get mixture; Grind thing altogether and mixed 40～100 mesh sieves with mixture, stir, add binding agent, granulate with 12～40 mesh sieves to make soft material, put in the baking oven 40～80 ℃ dry 1-4 hour, add the lubricant adjuvant, granulate makes granule, conventional method is made capsule, tablet, granule.
5. the preparation method of oral solid formulation as claimed in claim 3 is characterized in that this method is: the microcrystalline Cellulose of getting oxalic acid escitalopram and 1/3～2/3 amount ground 60～120 mesh sieves altogether, must grind thing altogether; With starch and remaining microcrystalline Cellulose and lactose, cross 60～120 mesh sieves, get mixture; Grind thing altogether and mixed 40～100 mesh sieves with mixture, stir, add binding agent, granulate with 12～40 mesh sieves to make soft material, put in the baking oven 40～80 ℃ dry 1-4 hour, add the lubricant adjuvant, granulate makes granule, conventional method is made capsule, tablet, granule.
6. the preparation method of oral solid formulation as claimed in claim 4 is characterized in that this method is:
The microcrystalline Cellulose of getting oxalic acid escitalopram and 1/2 amount ground 100 mesh sieves altogether, starch and remaining microcrystalline Cellulose and lactose are mixed, cross 100 mesh sieves, grind thing altogether and mixed 80 mesh sieves with mixture, stir, add binding agent and make soft material, granulate with 20 mesh sieves, put in the baking oven 60 ℃ of dryings 2 hours, reuse 20 mesh sieve granulate, add the lubricant adjuvant, make tablet.
7. the preparation method of oral solid formulation as claimed in claim 5 is characterized in that this method is:
The microcrystalline Cellulose of getting oxalic acid escitalopram and 1/2 amount ground 100 mesh sieves altogether, starch and remaining microcrystalline Cellulose and lactose are mixed, cross 100 mesh sieves, grind thing altogether and mixed 80 mesh sieves with mixture, stir, add binding agent and make soft material, granulate with 20 mesh sieves, put in the baking oven 60 ℃ of dryings 2 hours, reuse 20 mesh sieve granulate, add the lubricant adjuvant, make tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2009100780816A CN101474171B (en) | 2009-02-13 | 2009-02-13 | Oral solid preparation of escitalopram oxalate and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009100780816A CN101474171B (en) | 2009-02-13 | 2009-02-13 | Oral solid preparation of escitalopram oxalate and preparation method thereof |
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| CN101474171A CN101474171A (en) | 2009-07-08 |
| CN101474171B true CN101474171B (en) | 2011-04-20 |
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Families Citing this family (3)
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| 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 |
| CN106038501A (en) * | 2016-06-30 | 2016-10-26 | 北京万全德众医药生物技术有限公司 | Escitalopram oxalate oral disintegrating tablet and preparation method thereof |
| CN106018618B (en) * | 2016-07-05 | 2018-06-22 | 湖南洞庭药业股份有限公司 | Escitalopram oxalate tablet composition and quality control method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006123243A2 (en) * | 2005-05-20 | 2006-11-23 | Aurobindo Pharma Limited | Pharmaceutical dosage forms comprising escitalopram in form of granules |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006123243A2 (en) * | 2005-05-20 | 2006-11-23 | Aurobindo Pharma Limited | Pharmaceutical dosage forms comprising escitalopram in form of granules |
Non-Patent Citations (1)
| Title |
|---|
| 张强，武风兰主编.药剂学.北京大学医学出版社,2003,174页. * |
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Owner name: SICHUAN KELUN PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SICHUAN PEARL PHARMACEUTICAL CO., LTD. Effective date: 20120330 |
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Effective date of registration: 20120330 Address after: 610500, No. 520, industrial road, Xindu District, Xindu, Sichuan, Chengdu Patentee after: Sichuan Kelun Pharmaceutical Co., Ltd. Address before: 642350 Anyue County Industrial Park, Sichuan Patentee before: Sichuan Pearl Pharmaceutical Co., Ltd. |