CN103860487B - A kind of ratio karoo amine slice and preparation technology thereof - Google Patents
A kind of ratio karoo amine slice and preparation technology thereof Download PDFInfo
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- CN103860487B CN103860487B CN201210524949.2A CN201210524949A CN103860487B CN 103860487 B CN103860487 B CN 103860487B CN 201210524949 A CN201210524949 A CN 201210524949A CN 103860487 B CN103860487 B CN 103860487B
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- bicalutamide
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- primojel
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- lactose hydrate
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Abstract
The invention belongs to pharmaceutical technology field, be specifically related to a kind of bicalutamide tablet and preparation technology.The new formula that the present invention selects have employed new technique, overcomes the deficiency of existing technique, it is adaptable to industrialized production, and product quality improves, and dissolution is good.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to a kind of bicalutamide tablet and preparation technology, be used for treating prostate cancer.
Background technology
Current carcinoma of prostate sickness rate in worldwide is higher, and the bigger treatment difficulty of misery because sick body being caused when it is fallen ill, and present carcinoma of prostate is the second largest lethal malignant tumor of male.Carcinoma of prostate is relevant with androgen, reduces the contents level of internal androgen, is the common method for the treatment of carcinoma of prostate.The androgen antagonist medicine of many nonsteroidals is used clinically for treatment carcinoma of prostate, and wherein bicalutamide is most widely used androgen antagonist medicine in worldwide, in particular in the treatment of carcinoma of prostate.
Bicalutamide is the general term of Astrazeneca AB androgen antagonist medicine Kang Shi get, its chemistry is by name: 2-hydroxyl-2-first-N-[4-amino-3-(trifluoromethyl) phenyl]-3-[(4-fluorophenyl) sulfur sulfone] propionic acid amide., and the structural formula of bicalutamide is as follows:
Bicalutamide is to apply maximum anti-androgens malignant prostate cancer medicines clinically now.This product and LHRH share the treatment that can be applicable to advanced prostate cancer, can reduce various toxic and side effects 70%, and effect is higher than flutamide, be the fastest-rising antitumor drug of current sales volume compared with first generation androgen antagonist his glue of medicine fluorine.Bicalutamide dosage is 50mg/ every day clinically now, and recently, the 150mg dosage of this product is used clinically for early prostate cancer, and its therapeutic effect is identical with the curative effect carrying out male castration, has wide application space.It addition, the low dose of bicalutamide applies also in the treatment of some androgen-dependent disorders, low dose of bicalutamide can treat female hirsutism, acne.Bicalutamide also can treat prostatic hyperplasia.Therefore, bicalutamide has good potential applicability in clinical practice.
Bicalutamide has optical activity, and pharmaceutical research shows, the activity of its laevoisomer is 60 times of dextroisomer, in vivo in process, and mainly laevoisomer generation effect, high with receptor protein combination rate.Same curative effect, if adopting laevoisomer, can at least reduce half consumption.Therapeutic dose can be effectively reduced hence with individual isomer, reduce side effect.
Summary of the invention
The technical problem to be solved is in that to overcome above-mentioned weak point, and research design is suitable to the ratio karoo amine slice production technology of industrialized production.
The technique of the present invention is based on following test:
Ratio karoo amine slice mainly investigates the characteristics such as the dissolution of tablet when screening formula, to determine optimum formula.The invention provides a kind of bicalutamide tablet preparation, said preparation is made up of following composition, every 1000:
Bicalutamide 50g
One Lactose hydrate 105.4g
Primojel 4g
HPMC0.6g
Magnesium stearate 4g
Purified water 29g
The present invention another object is that the preparation technology providing a kind of bicalutamide tablet preparation, and this technique comprises the following steps:
1, bicalutamide below micronization 25um, 100 mesh sieves crossed respectively by adjuvant；
2, the bicalutamide of recipe quantity, a Lactose hydrate, primojel are claimed；
3, the bicalutamide of recipe quantity, a Lactose hydrate, primojel are put into high speed wet granulator and open stirring at low speed 4min, high-speed stirred 3min, add 2%HPMC aqueous solution 30g and granulate, 120 revs/min of 5min of stirring at low speed；
4,65～75 DEG C of aeration-dryings 1-2 hour, 16 mesh sieve granulate；
5, add recipe quantity magnesium stearate, mix 50 turns 15 minutes, the content of sampling and measuring intermediate and moisture；
6, according to intermediates content measurement result, element sheet weight is calculated by every plain sheet containing bicalutamide 50mg
7, tabletting, obtains product.
The present invention has features compared with prior art:
Bicalutamide is carried out micronization.Micronization technology utilization ratio in the formulation is wide, especially insoluble drug, can reach to increase the purpose of dissolution by micronization technology.
The available Noyes-Whitney equation of the dissolution theory of solid dosage forms describes,
dc/dt=kS(Cs-C)
Dc/dt is dissolution rate, and k is dissolution rate constant, and S is that medical surfaces amasss, and Cs is the dissolution of medicine, and C is drug concentration in solution.
Above formula shows, medicine dissolution rate from solid dosage forms is directly proportional to the drug concentration gradient (Cs-C) in k, the surface area of drug particle, dissolubility, dissolution medium.For given medicine, Cs is constant.Above formula shows, as increased the surface area S of medicine, such as micronization, it is possible to increase the dissolution of medicine.
Bicalutamide is carried out micronization.So producing and can normally continuously perform, and product quality is easily controllable, the dissolution of product is guaranteed.
The technique of the present invention and existing technique have carried out the comparison of degree of melting out, and the dissolution of result display present invention process is high and data stabilization.
Detailed description of the invention
Embodiment 1-3:
Operating process:
1, bicalutamide below micronization 25um, 100 mesh sieves crossed respectively by adjuvant；
2, the bicalutamide of recipe quantity, a Lactose hydrate, primojel are claimed；
3, the bicalutamide of recipe quantity, a Lactose hydrate, primojel are put into high speed wet granulator and open stirring at low speed 4min, high-speed stirred 3min, add 2%HPMC aqueous solution 30g and granulate, 120 revs/min of 5min of stirring at low speed；
4,65～75 DEG C of aeration-dryings 1-2 hour, 16 mesh sieve granulate；
5, add recipe quantity magnesium stearate, mix 50 turns 15 minutes, the content of sampling and measuring intermediate and moisture；
6, according to intermediates content measurement result, element sheet weight is calculated by every plain sheet containing bicalutamide 50mg
7, tabletting, obtains product.
Dissolution takes this product, according to dissolution method, with 1.0% sodium dodecyl sulfate solution 1000ml for solvent, rotating speed is 50 turns per minute, operates in accordance with the law, solution 10ml is taken through 45 minutes, filter, take filtrate 5ml and put in 25ml measuring bottle, add 1.0% sodium dodecyl sulfate solution to scale, shake up, as need testing solution.Separately take the bicalutamide reference substance of the dry constant weight of 105.C O.1g, put in 200ml measuring bottle, add oxolane 5ml, jolting makes dissolving, then adds 1.0% sodium dodecyl sulfate solution to scale, shakes up, precision measures 2.Oml in 100ml measuring bottle, add 1.0% sodium dodecyl sulfate solution and be diluted to scale, shake up, as contrast solution.According to spectrophotography (two annex IVA of China's coastal port), measure absorbance respectively at 271nm wavelength place.Calculate the stripping quantity of every.Limit is the 75% of labelled amount, should meet regulation.
The dissolution testing result of product of the present invention:
It can be seen that after bicalutamide micronization (10um～below 25um), dissolution is all right, and dissolution is all higher than 95% from above 3 examples.
Claims (1)
1. a bicalutamide tablet, it is characterised in that said preparation is made up of the composition of following weight:
Every 1000:
Bicalutamide 50g
One Lactose hydrate 105.4g
Primojel 4g
HPMC0.6g
Magnesium stearate 4g
Purified water 29g
Its preparation technology comprises the following steps:
Bicalutamide micronization less than 25 μm, 100 mesh sieves crossed respectively by adjuvant, claim the bicalutamide of recipe quantity, one Lactose hydrate, primojel, by the bicalutamide of recipe quantity, one Lactose hydrate, primojel puts into high speed wet granulator and opens stirring at low speed 4 minutes, high-speed stirred 3 minutes, add 2%HPMC aqueous solution 30g to granulate, stirring at low speed 120 revs/min 5 minutes, 65～75 DEG C of aeration-dryings 1-2 hour, 16 mesh sieve granulate, add recipe quantity magnesium stearate, mix 50 revs/min 15 minutes, the content of sampling and measuring intermediate and moisture, according to intermediates content measurement result, element sheet weight is calculated containing bicalutamide 50mg by every plain sheet, tabletting, obtain product.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210524949.2A CN103860487B (en) | 2012-12-10 | 2012-12-10 | A kind of ratio karoo amine slice and preparation technology thereof |
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| CN201210524949.2A CN103860487B (en) | 2012-12-10 | 2012-12-10 | A kind of ratio karoo amine slice and preparation technology thereof |
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| CN103860487B true CN103860487B (en) | 2016-07-06 |
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| CN106692100A (en) * | 2016-12-27 | 2017-05-24 | 上海朝晖药业有限公司 | Preparation method of bicalutamide tablet |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101199486A (en) * | 2006-12-13 | 2008-06-18 | 上海复星医药（集团）股份有限公司 | Ratio karoo amine slice and preparing technique thereof |
| CN101478963A (en) * | 2006-07-07 | 2009-07-08 | 万能药生物有限公司 | Methods and compositions for producing anti-androgenic effects |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101478963A (en) * | 2006-07-07 | 2009-07-08 | 万能药生物有限公司 | Methods and compositions for producing anti-androgenic effects |
| CN101199486A (en) * | 2006-12-13 | 2008-06-18 | 上海复星医药（集团）股份有限公司 | Ratio karoo amine slice and preparing technique thereof |
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