CN103948570A - Exemestane sustained-release capsule - Google Patents

Exemestane sustained-release capsule Download PDF

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Publication number
CN103948570A
CN103948570A CN201410157922.3A CN201410157922A CN103948570A CN 103948570 A CN103948570 A CN 103948570A CN 201410157922 A CN201410157922 A CN 201410157922A CN 103948570 A CN103948570 A CN 103948570A
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China
Prior art keywords
exemestane
slow releasing
releasing capsule
acrylic resin
binding agent
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CN201410157922.3A
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Chinese (zh)
Inventor
赵辉
赵冠淇
苏天慧
胡晓川
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Individual
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Abstract

The invention discloses an exemestane sustained-release capsule. The exemestane sustained-release capsule is composed of 5-20wt% of exemestane, 58-95wt% of excipient, 3-10wt% of film coating material, 0-10wt% of wetting agent and 1-2wt% of adhesive; and a preparation method for the same comprises the step of preparing by (1) an extrusion rounding method, (2) a powder coating method, and (3) a liquid deposition method to obtain the exemestane sustained-release capsule.

Description

A kind of exemestane slow releasing capsule
Invention field
The present invention relates to a kind of slow releasing capsule, particularly a kind of exemestane slow releasing capsule.
Background of invention
Breast carcinoma is one of common malignant tumor of world women.The positive increase year after year of sickness rate, in current elderly population, the age, what suffer from breast cancer accounted for 26% higher than the women of 65 years old, and wherein approximately 1/3 tumor growth needs high estrogen level to maintain, and has the feature of estrogen-dependent.Estrogen-dependent type breast carcinoma is apt to occur in postmenopausal women.Estrogen-dependent type patient with breast cancer commonly uses antiestrogen, and tamoxifen is as first-line treatment medicine, but when tamoxifen is brought into use, effect is better, and life-time service just easily produces drug resistance, causes disease relapse.The another kind of mechanism of action is different from the arimedex of tamoxifen, effective to above-mentioned drug resistance patient.At present the good arimedex of curative effect is Formestane, clinical use at home and abroad, but Formestane can only drug administration by injection, and oral invalid.
The growth of breast cancer cell can be dependent on estrogenic existence, and the main aromatase in peripheral tissues of estrogen (estrone and estradiol) during women circulated after menopause is transformed the androgen in adrenal gland and ovary (androstenedione and testosterone).By suppressing aromatase, to stop estrogen production be the method for hormonal dependent breast carcinoma after a kind of effective as selective treatment menopause.Exemestane is that a kind of irreversibility is stayed body aromatase inactivator, similar to the natural substrate androstenedione of this enzyme in structure, pseudo-substrate for aromatase, can be by being irreversibly combined and making its inactivation with the avtive spot of this enzyme, thus the estrogen level in menopausal women blood circulation obviously reduced.
According to reported literature, after the oral radiolabeled exemestane of the healthy women of menopause, absorb rapidly, at least 42% exemestane is absorbed at gastrointestinal tract; After edible High fat meal, exemestane in blood plasma (Exemestane) level rises approximately 40%.Exemestane extensively distributes in each tissue, and its plasma protein binding rate is 90%.The metabolic rate of exemestane is extensive, mainly by oxidation and the reduction of 17-position ketone group of 6-position methylene, carry out metabolism, metabolite non-activity or suppress aromatase activity a little less than, its metabolite is mainly drained from urine and excrement, approximately respectively account for 40% left and right, the original shape medicine of discharging in urine is lower than 1% of dosage.The average t1/2 of exemestane is 24 hours.The more healthy postmenopausal women of absorption of breast carcinoma postmenopausal women in late period is fast, and peak time is respectively 1.2 hours and 2.9 hours.After repeat administration, the more healthy postmenopausal women of average oral clearance of breast carcinoma patients with terminal is low by 45%, and circulation in level higher; Its average A UC is 2 times of healthy women.
Exemestane is a kind of potent, single-minded, irreversible arimedex, is applicable to treat metastatic tumour and the menopausal women patient with breast cancer of estrogen-dependent type, and oral effective, and toxic and side effects is little, easily by patient, is accepted.
Research shows, exemestane dissolubility is general, and exemestane slow releasing capsule prepared by the present invention has the slow-release function of 24 hours, can effectively control the burst size of medicine, and safety, effectiveness are better; Because being pilule, large at gastrointestinal tract distribution area, improved exemestane dissolubility, bioavailability is high, and zest is little; Can make blood drug level reach rapidly curative effect concentration, maintain steady, long valid density, blood concentration fluctuation is little; Be beneficial to the toxic and side effects that reduces medicine; Reduced patient's medicining times; Steady quality.
Summary of the invention
The object of the present invention is to provide a kind of exemestane slow releasing capsule, it can overcome current exemestane general formulation release amount of medicine can not effectively control, and causes safety, the poor shortcoming of effectiveness, and can reduce medication accumulated dose and good effect.Concrete technical scheme is as follows:
On the one hand, the present invention relates to a kind of exemestane slow releasing capsule, it is comprised of exemestane, excipient, thin film coating material, wetting agent, stabilizing agent and binding agent, wherein each component by weight exemestane be 5~20%, excipient is 58~95%, thin film coating material is 3~10%, and wetting agent is 0~10% and binding agent 1~2%.
In some embodiments, exemestane slow releasing capsule of the present invention, it is a kind of pilule with slow releasing function.
In some embodiments, exemestane slow releasing capsule of the present invention, wherein, the excipient in described exemestane slow releasing capsule is the one or more combination in cellulose family, starch, lactose and calcium bicarbonate.
In other embodiments, exemestane slow releasing capsule of the present invention, wherein, the cellulose family excipient in described exemestane slow releasing capsule is ethyl cellulose, hydroxypropyl emthylcellulose, microcrystalline Cellulose, acrylic resin I, acrylic resin II, acrylic resin III or acrylic resin IV.
Some embodiments therein, exemestane slow releasing capsule of the present invention, wherein, the thin film coating material in described exemestane slow releasing capsule is one or both combinations in Aquacoat and aqueous acrylic resin dispersion.
Some embodiments therein, exemestane slow releasing capsule of the present invention, the wetting agent in wherein said exemestane slow releasing capsule is one or both the mixing in water or ethanol.
Some embodiments therein, exemestane slow releasing capsule of the present invention, wherein, the binding agent in described exemestane slow releasing capsule is the one or more combination in cellulose family, resinae, saccharide, gelatin.
Some embodiments therein, exemestane slow releasing capsule of the present invention, wherein, the cellulose family binding agent in described exemestane slow releasing capsule is water or the alcoholic solution of hydroxypropyl emthylcellulose, ethyl cellulose.
Some embodiments therein, exemestane slow releasing capsule of the present invention, wherein, the resinae binding agent in described exemestane slow releasing capsule is acrylic resin I, acrylic resin II, acrylic resin III or acrylic resin IV.
Some embodiments therein, exemestane slow releasing capsule of the present invention, wherein, the saccharide binding agent in described exemestane slow releasing capsule is maltose.
The specific embodiment
The preparation technology of above-mentioned exemestane slow releasing capsule, it adopts following several technique to prepare:
(1) extrude spheronization: utilize and extrude round as a ball comminutor, crude drug and mixed with excipients are crossed to 80 eye mesh screens, after with adhesive, mixed powder being squirted, extrude the round as a ball ball of making in extruding round as a ball comminutor, after being dried, sieve and obtain the pastille micropill that certain order is counted size.In fluidized bed coating pot, with Aquacoat, carry out coating and get final product;
(2) powder coating method: utilize atresia coating pan, Corm Eleocharitis type coating pan, fluid bed top spray (or end spray) seed-coating machine, fluid bed tangent line spray ball mechanism ball.The Corm Eleocharitis type coating pan of take is example: medicated powder and mixed with excipients are crossed to 80 eye mesh screens, get the micropill (sucrose ball or microcrystalline Cellulose ball) of certain order number and put into Corm Eleocharitis type coating pan, after micropill surface being squirted with adhesive, a small amount of mixed powder is sprinkled in pot, make mixed powder be wrapped in uniformly the surface of micropill, and then squirt micropill surface and add again powder, until mixed powder all adds, after being dried, sieve and obtain the pastille micropill that certain order is counted size.In fluidized bed coating pot, with Aquacoat, carry out coating and get final product;
(3) liquid phase deposition: can utilize atresia coating pan, Corm Eleocharitis type coating pan, fluid bed top spray (or end spray) seed-coating machine, fluid bed tangent line spray ball mechanism ball.The Corm Eleocharitis type coating pan of take is example: the micropill (sucrose ball or microcrystalline Cellulose ball) of getting certain order number is put into Corm Eleocharitis type coating pan, medicated powder and excipient is molten in adhesive, the Surface Edge spray limit that mixed liquor is sprayed onto to micropill is dry, until mixed liquor has all sprayed, after being dried, sieve and obtain the pastille micropill that certain order is counted size.In fluidized bed coating pot, with Aquacoat, carry out coating and get final product.
Embodiment
Embodiment 1:
An exemestane slow releasing capsule, it is comprised of 5% exemestane, 90% excipient, 3% thin film coating material, 1% wetting agent and 1% binding agent.Wherein excipient is microcrystalline Cellulose, and thin film coating material is Aquacoat, and wetting agent is 75% alcoholic solution, and binding agent is the aqueous solution of hydroxypropyl emthylcellulose.Exemestane slow releasing capsule a preparation technology, it adopts following technique to prepare:
Spheronization is extruded in utilization: utilize and extrude round as a ball comminutor; crude drug was mixed to 80 eye mesh screens with microcrystalline Cellulose; after mixed powder being squirted with the aqueous solution of hydroxypropyl emthylcellulose, extrude the round as a ball ball of making in extruding round as a ball comminutor; after dry, sieve and obtain the pastille micropill that certain order is counted size, in fluidized bed coating pot, with Aquacoat, carry out coating and get final product.
Embodiment 2
An exemestane slow releasing capsule, wherein, described slow releasing capsule is comprised of 20% exemestane, 63% excipient, 10% thin film coating material, 5% wetting agent and 2% binding agent.Wherein excipient is starch, and thin film coating material is Aquacoat, and wetting agent is aqueous solution, and binding agent is the alcoholic solution of polyethylene pyrroles protective embankment ketone.
Exemestane slow releasing capsule a preparation technology, it adopts following technique to prepare:
Powder coating method: utilize atresia coating pan, Corm Eleocharitis type coating pan, fluid bed top spray (or end spray) seed-coating machine, fluid bed tangent line spray pellet processing machine to make ball.The Corm Eleocharitis type coating pan of take is example: medicated powder was mixed to 80 eye mesh screens with starch, get the micropill (sucrose ball or microcrystalline Cellulose ball) of 30-35 order number and put into Corm Eleocharitis type coating pan, after micropill surface being squirted with the alcoholic solution of polyethylene pyrroles protective embankment ketone, a small amount of mixed powder is sprinkled in pot, make mixed powder be wrapped in uniformly the surface of micropill, and then squirt micropill surface and add again powder, until mixed powder all adds, after being dried, sieve and obtain the pastille micropill that certain order is counted size.In fluidized bed coating pot, with Aquacoat, carry out coating and get final product.
Embodiment 3
An exemestane slow releasing capsule, wherein, described slow releasing capsule is comprised of 10% exemestane, 73% excipient, 5% thin film coating material, 10% wetting agent and 2% binding agent.Wherein excipient is starch, and thin film coating material is Aquacoat, and wetting agent is aqueous solution, and binding agent is the alcoholic solution of hydroxypropyl emthylcellulose.
A preparation technology for exemestane slow releasing capsule, it adopts following technique to prepare:
Liquid phase deposition: can utilize atresia coating pan, Corm Eleocharitis type coating pan, fluid bed top spray (or end spray) seed-coating machine, fluid bed tangent line spray ball mechanism ball.The Corm Eleocharitis type coating pan of take is example: get certain 30-35 object micropill (sucrose ball or microcrystalline Cellulose ball) and put into Corm Eleocharitis type coating pan, medicated powder and excipient is molten in adhesive, the Surface Edge spray limit that mixed liquor is sprayed onto to micropill is dry, until mixed liquor has all sprayed, after being dried, sieve and obtain the pastille micropill that certain order is counted size.In fluidized bed coating pot, with Aquacoat, carry out coating and get final product.
Clinical case is analyzed
Clinical case analysis of the present invention: this product clinical trial, obtain good safety, efficiency evaluation, and bioavailability is high, in vivo sustainable 24 hours drug releases.Because exemestane slow releasing capsule is that pilule is large at gastrointestinal tract distribution area, bioavailability is high, therefore irritating property is little, be subject to the digestive tract conveying food rhythm and pace of moving things to affect little (as pylorus is closed etc.), blood drug level can be reached rapidly to curative effect concentration, and maintain steady, long valid density, blood concentration fluctuation is little, be conducive to reduce the toxic and side effects of medicine, below adopt several routine typical clinical cases to analyze:
Clinical case l: patient A, female, 55 years old, suffer from postmenopausal women with advanced breast carcinoma, under doctor advised, use exemestane slow releasing capsule, take every day once, to take continuously 4 weeks, symptom has obvious alleviation.Explanation thus: the features such as exemestane slow releasing capsule drug effect is fast, and effect is lasting, and toxic and side effects is little.
Clinical case 2: patient B, female, 50 years old, suffer from postmenopausal women with advanced breast carcinoma, under doctor advised, use exemestane slow releasing capsule, take every day once, to take continuously 4 weeks, gross tumor volume has obviously and reduces.Explanation thus: the features such as exemestane slow releasing capsule drug effect is fast, and effect is lasting, and toxic and side effects is little.
Clinical case 3: patient C, female, 65 years old, postmenopausal women with advanced breast carcinoma started to take exemestane slow releasing capsule under doctor's suggestion after diagnosing, takes every day once, took continuously 4 weeks, and gross tumor volume has obviously and reduces.Explanation thus: exemestane slow releasing capsule is rapid-action, and dosage is few, taking convenience, toxic and side effects is little.
Clinical case 4: patient D, female, 60 years old, suffer from after diagnosing postmenopausal women with advanced breast carcinoma, under doctor's suggestion, start to take exemestane slow releasing capsule, take every day once, take continuously 4 weeks, gross tumor volume has obviously and reduces, and dosage is little, reduce the toxic and side effects of medicine, through treatment patient symptom, obviously improve.
Therefore superiority of the present invention and technique effect are: (1) exemestane slow releasing capsule has the slow-release function of 24 hours, can effectively control the burst size of medicine, and safety, effectiveness are better; (2) exemestane slow releasing capsule is that pilule is large at gastrointestinal tract distribution area, and bioavailability is high, and zest is little; (3), because particle diameter is little, be subject to the digestive tract conveying food rhythm and pace of moving things to affect little (as pylorus is closed etc.); (4) exemestane controlled release micro pill can make blood drug level reach rapidly curative effect concentration, and maintains steady, long valid density, and blood concentration fluctuation is little; (5) good fluidity of micropill, size evenly, is easy to process (as coating, divided dose); (6) exemestane slow releasing capsule is conducive to reduce the toxic and side effects of medicine; (7) the exemestane slow releasing capsule dosage form more common than this medicine reduced the accumulated dose of medication, reduced patient's medicining times; (8) new formula, steady quality have been adopted; (9) in the preparation process of exemestane slow releasing capsule, can adopt framing structure, film control structure or skeleton blooming control structure.

Claims (10)

1. an exemestane slow releasing capsule, it is comprised of exemestane, excipient, thin film coating material, wetting agent and binding agent, wherein each component by weight exemestane be 5~20%, excipient is 58~95%, thin film coating material is 3~10%, and wetting agent is 0~10% and binding agent 1~2%.
2. exemestane slow releasing capsule according to claim 1, it is a kind of pilule with slow releasing function.
3. exemestane slow releasing capsule according to claim 1, wherein, the excipient in described exemestane slow releasing capsule is the one or more combination in cellulose family, starch, lactose and calcium bicarbonate.
4. exemestane slow releasing capsule according to claim 3, wherein, the cellulose family excipient in described exemestane slow releasing capsule is ethyl cellulose, hydroxypropyl emthylcellulose, microcrystalline Cellulose, acrylic resin I, acrylic resin II, acrylic resin III or acrylic resin IV.
5. exemestane slow releasing capsule according to claim 1, wherein, the thin film coating material in described exemestane slow releasing capsule is one or both combinations in Aquacoat and aqueous acrylic resin dispersion.
6. exemestane slow releasing capsule according to claim 1, the wetting agent in wherein said exemestane slow releasing capsule is one or both the mixing in water or ethanol.
7. exemestane slow releasing capsule according to claim 1, wherein, the binding agent in described exemestane slow releasing capsule is the one or more combination in cellulose family, resinae, saccharide, gelatin.
8. exemestane slow releasing capsule according to claim 7, wherein, the cellulose family binding agent in described exemestane slow releasing capsule is water or the alcoholic solution of hydroxypropyl emthylcellulose, ethyl cellulose.
9. exemestane slow releasing capsule according to claim 7, wherein, the resinae binding agent in described exemestane slow releasing capsule is acrylic resin I, acrylic resin II, acrylic resin III or acrylic resin IV.
10. exemestane slow releasing capsule according to claim 7, wherein, the saccharide binding agent in described exemestane slow releasing capsule is maltose.
CN201410157922.3A 2014-04-18 2014-04-18 Exemestane sustained-release capsule Pending CN103948570A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114557975A (en) * 2022-03-04 2022-05-31 河南省人民医院 Sustained release tablet containing exemestane, process and use

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060246134A1 (en) * 2005-05-02 2006-11-02 Venkatesh Gopi M Timed, pulsatile release systems
CN101224210A (en) * 2006-12-13 2008-07-23 天津市弗兰德医药科技发展有限公司 Mizolastine sustained release capsule
CN101468023B (en) * 2007-12-26 2011-02-02 上海复星医药(集团)股份有限公司 Exemestane tablet and technique for preparing the same
CN101991553A (en) * 2009-08-21 2011-03-30 北京以岭生物工程有限公司 Exemestane tablet and preparation method thereof
WO2012079154A1 (en) * 2010-12-14 2012-06-21 Dalhousie University Selective estrogen receptor modulators

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060246134A1 (en) * 2005-05-02 2006-11-02 Venkatesh Gopi M Timed, pulsatile release systems
CN101224210A (en) * 2006-12-13 2008-07-23 天津市弗兰德医药科技发展有限公司 Mizolastine sustained release capsule
CN101468023B (en) * 2007-12-26 2011-02-02 上海复星医药(集团)股份有限公司 Exemestane tablet and technique for preparing the same
CN101991553A (en) * 2009-08-21 2011-03-30 北京以岭生物工程有限公司 Exemestane tablet and preparation method thereof
WO2012079154A1 (en) * 2010-12-14 2012-06-21 Dalhousie University Selective estrogen receptor modulators

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114557975A (en) * 2022-03-04 2022-05-31 河南省人民医院 Sustained release tablet containing exemestane, process and use
CN114557975B (en) * 2022-03-04 2023-04-25 河南省人民医院 Sustained release tablet containing exemestane, process and use thereof

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