CN103405394A - Metoprolol tartrate sustained release tablet and preparation method thereof - Google Patents
Metoprolol tartrate sustained release tablet and preparation method thereof Download PDFInfo
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- CN103405394A CN103405394A CN2013103682169A CN201310368216A CN103405394A CN 103405394 A CN103405394 A CN 103405394A CN 2013103682169 A CN2013103682169 A CN 2013103682169A CN 201310368216 A CN201310368216 A CN 201310368216A CN 103405394 A CN103405394 A CN 103405394A
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- release tablet
- metoprolol
- metoprolol tartrate
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Abstract
The invention provides a metoprolol tartrate sustained release tablet. The metoprolol tartrate sustained release tablet is prepared from the following components in percentage by mass: 100 of metoprolol tartrate, 60-80 of retardant, 20-40 of filling agent, 2-10 of lubricating agent, 50-90 of adhesive and 2.5-4 of film coating powder. Aiming at the problem that adhesive brewing is easily caused in production because the metoprolol tartrate is easy to dissolve in water, the invention provides a two-step granulation method comprising the steps of respectively preparing medicine contained granules and blank granules, drying the medicine contained granules and the blank granules, totally mixing the medicine contained granules and the blank granules and tabletting, so that the problem of adhesive brewing in tabletting is solved. In addition, the metoprolol tartrate is strong in moisture absorption property and bitter in taste, and a coating layer can be used for improving the stability of the metoprolol tartrate and masking the bitter taste of the metoprolol tartrate. The metoprolol tartrate sustained release tablet has the advantages that the components of the auxiliary materials are simple, the operation is convenient, the prepared granules are good in flowability, strong in adhesive resistance and incapable of causing adhesive brewing during tabletting, and the coating layer can be used for improving the stability of a drug and masking the bitter tastes of active ingredients and has no affect to the release rate of the tablet. The metoprolol tartrate sustained release tablet is suitable for industrial production and relatively high in application value.
Description
Technical field
The present invention relates to pharmaceutical preparation, be specifically related to slow releasing preparation, relate in particular to a kind of metoprolol sustained-release tablet and preparation method thereof.
Background technology
Spectinomycin hydrochloride, chemical name are 1-isopropylamino-3-［ p-(2-methoxyethyl) phenoxy group ］-2-propanol L (+)-tartrate, are a kind of β that heart is had to high selectivity
1Receptor blocking agent, structural formula is as follows:
Spectinomycin hydrochloride is β optionally
1Blocker, heart is had to larger selectively acting, be used for the treatment of hypertension, angina pectoris, myocardial infarction, hypertrophic cardiomyopathy, dissection of aorta, arrhythmia, hyperthyroidism, heart neurosis etc., in recent years also for the treatment of heart failure.Research shows, metoprolol can effectively be treated hypertension, and life-time service can significantly reduce the death risk of patients with heart failure, is one of first-selection of depressor.At present, China for clinical be the metoprolol ordinary tablet, its removing half-life is 3～4h, need take medicine every day more than 2 times, and spectinomycin hydrochloride dissolubility in water is very large, is unfavorable for the sustained drug effect, therefore, the spectinomycin hydrochloride medicine is made slow releasing preparation, took medicine once in one day, and improved drug bioavailability, for the long-term hypertension class disease for the treatment of even throughout one's life, can improve patient compliance, heighten the effect of a treatment.Usually, the slow release formulation of medicine is the Tablet and Capsula agent.And tablet is with respect to capsule, the one, the tablet ratio is easier to take, and can not cause dysphagia; The 2nd, tablet does not need softgel shell, more acceptant concerning the patient of dislike capsule softgel shell; The 3rd, on cost of manufacture the cost less, therefore, often can select tablet.Yet, because spectinomycin hydrochloride dissolubility in water is very large, actual measurement can reach 1.5g/mL, and in traditional wet granulation, majority selects starch, dextrin or amylodextrin to dissolve the punching slurry as binding agent by purified water, in the tabletting process, easily cause glutinous punching, have a strong impact on production.Thereby the adjuvant that How to choose is suitable and preparation, solve the glutinous problem etc. of rushing in the spectinomycin hydrochloride production process, is urgently to be resolved hurrily.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, and the research design mobility of particle is good, and anti-stickiness is strong, is suitable for the metoprolol sustained-release tablet of suitability for industrialized production.
The invention provides a kind of metoprolol sustained-release tablet.Described metoprolol sustained-release tablet is grouped into by the one-tenth of following quality proportioning:
Spectinomycin hydrochloride 100, blocker 60～80, filler 20～40, lubricant 2～10, binding agent 50～90, film coating powder 2.5～4.
Described blocker is selected from one or more in hypromellose (K100LV, K100M, K4M, E50 or SH4000), is preferably HPMC K4M and E50 and forms with quality proportioning 1:0.15～0.6.
Described filler is selected from one or more in lactose, microcrystalline Cellulose, mannitol or starch, is preferably lactose;
Described lubricant is selected from one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, Polyethylene Glycol or hydrogenated vegetable oil, is preferably magnesium stearate and silicon dioxide and forms with quality proportioning 1:0.2～2.
Metoprolol sustained-release tablet of the present invention is grouped into by the one-tenth of preferred following quality proportioning:
| Spectinomycin hydrochloride | 100 |
| Blocker hydroxypropyl methylcellulose K4M | 45 |
| Blocker hydroxypropyl methylcellulose E50 | 25 |
| The filler lactose | 30 |
| Lubricant silicon dioxide | 2 |
| Magnesium stearate lubricant | 4 |
| 80% ethanol | 66 |
| 30% ethanol | 22.7 |
| The film coating powder | 3.1 |
Another object of the present invention has been to provide the preparation method of above-mentioned a kind of metoprolol tartrate extended release tablets, and the method comprises the following steps:
(1) by spectinomycin hydrochloride and a kind of blocker mix homogeneously, add the alcoholic solution of 60%-90%, be preferably 80% alcoholic solution and prepare soft material, cross 20 mesh sieves and make medicine-containing particle;
(2) by filler and another blocker mix homogeneously, add the alcoholic solution of 60%-90%, be preferably 80% alcoholic solution soft material processed, cross 20 mesh sieves and make blank granule;
(3) by medicine-containing particle and the rear mistake 20 mesh sieve granulate of 60 ± 5 ℃ of heated-air circulation oven dryings of blank granule, add magnesium stearate and micropowder silica gel mix homogeneously;
(4) tabletting;
(5) with stomach dissolved film coating pre-mix dose, make coating solution, coating, obtain metoprolol tartrate extended release tablets.
The coating solution of described step (5), for by the stomach dissolution type film coating powder by commercially available, to join in 30% alcoholic solution of stirring, is mixed with the suspension of stomach dissolution type film coating powder solid content 12%.
The present invention selects hypromellose as blocker, for spectinomycin hydrochloride soluble in water, be desirable slow-release material, but glutinous punching still occurs when tabletting, for solving the glutinous problem of rushing, using high concentration ethanol solution as solvent, substep is granulated, and like this, medicine-containing particle can suitably reduce solvent, by further drying, effectively reduce granule humidity, solved the glutinous problem of rushing of spectinomycin hydrochloride tabletting.
The tablet release that the present invention makes is good.In dissolution in vitro test, discharged the 25%～45%, 4th hour in first hour and discharge the 40%～75%, 8th hour and discharge more than 75%, can the Stable Release medicine, meet the Chinese Pharmacopoeia standard.In addition, the spectinomycin hydrochloride hygroscopicity is strong, bitter in the mouth, coatings can improve stability of drug products, covers the bitterness of principal agent, and coatings on the tablet release without a bit impact.
The mobility of particle that the present invention makes is good, and anti-stickiness is strong, during tabletting, can not cause glutinous punching, is suitable for suitability for industrialized production, and larger using value is arranged.
The specific embodiment
The present invention is further detailed explanation below in conjunction with embodiment.Embodiment provides by way of example, is not construed as limiting the invention.
Embodiment 1
| Spectinomycin hydrochloride | 1000g |
| Hydroxypropyl methylcellulose K4M | 500g |
| Hydroxypropyl methylcellulose E50 | 200g |
| Lactose | 300g |
| Silicon dioxide | 20g |
| Magnesium stearate | 40g |
| 80% ethanol | 660g |
| 30% ethanol | 227g |
| Film coating powder (stomach dissolution type) | 31g |
Preparation: by spectinomycin hydrochloride, hypromellose E50, in the KJZ-10 Quick-stirring granulator, 5 minutes mix homogeneously of rapid stirring, add 5 minutes soft materials processed of 80% alcoholic solution 220g rapid stirring, then YK-160 oscillating granulator 20 mesh sieves are granulated, as medicine-containing particle, by lactose, HPMC K4M mix homogeneously, 80% alcoholic solution 440g, with the legal system soft material, granulate, as blank granule, medicine-containing particle and blank granule are respectively in the CT-C-F heated-air circulation oven, 60 ± 5 ℃ of dryings 7 hours, cross YK-160 oscillating granulator 20 mesh sieve granulate, add silicon dioxide and magnesium stearate mix homogeneously, the ZP33 rotary tablet machine, the circular recessed stamping of Φ 8.5mm, by the film coating powder (stomach dissolution type) of buying from Shanghai Colorcon Coating Technology Co., Ltd, join in 30% alcoholic solution of stirring, be made into the suspension of film coating powder (stomach dissolution type) solid content 12%, continue to stir 45 minutes, in the coating process, uninterruptedly stir, coating weightening finish>1.0%, totally 10000.
Testing result:
Embodiment 2
| Spectinomycin hydrochloride | 1000g |
| Hydroxypropyl methylcellulose K4M | 450g |
| Hydroxypropyl methylcellulose E50 | 250g |
| Lactose | 300g |
| Silicon dioxide | 20g |
| Magnesium stearate | 40g |
| 80% ethanol | 660g |
| 30% ethanol | 227g |
| Film coating powder (stomach dissolution type) | 31g |
Preparation: by spectinomycin hydrochloride, hypromellose E50, in the KJZ-10 Quick-stirring granulator, 5 minutes mix homogeneously of rapid stirring, add 80% alcoholic solution 230g, 5 minutes soft materials processed of rapid stirring, then YK-160 oscillating granulator 20 mesh sieves are granulated, as medicine-containing particle, by lactose, HPMC K4M mix homogeneously, 80% alcoholic solution 430g, with the legal system soft material, granulate, as blank granule, medicine-containing particle and blank granule are respectively in the CT-C-F heated-air circulation oven, 60 ± 5 ℃ of dryings 7 hours, cross YK-160 oscillating granulator 20 mesh sieve granulate, add silicon dioxide and magnesium stearate mix homogeneously, the ZP33 rotary tablet machine, the circular recessed stamping of Φ 8.5mm, purchase is from the film coating powder (stomach dissolution type) of Shanghai Colorcon Coating Technology Co., Ltd, join in 30% alcoholic solution of stirring, be made into the suspension of film coating powder (stomach dissolution type) solid content 12%, continue to stir 45 minutes, in the coating process, uninterruptedly stir, coating weightening finish>1.0%, totally 10000.
Testing result:
Embodiment 3
| Spectinomycin hydrochloride | 1000g |
| Hydroxypropyl methylcellulose K4M | 550g |
| Hydroxypropyl methylcellulose E50 | 100g |
| Lactose | 350g |
| Silicon dioxide | 20g |
| Magnesium stearate | 40g |
| 80% ethanol | 660g |
| 30% ethanol | 227g |
| Film coating powder (stomach dissolution type) | 31g |
Preparation: by spectinomycin hydrochloride, hypromellose E50, in the KJZ-10 Quick-stirring granulator, 5 minutes mix homogeneously of rapid stirring, add 5 minutes soft materials processed of 80% alcoholic solution 200g rapid stirring, YK-160 oscillating granulator 20 mesh sieves are granulated, as medicine-containing particle, by lactose, HPMC K4M mix homogeneously, 80% alcoholic solution 460g, with the legal system soft material, granulate, as blank granule, medicine-containing particle and blank granule are respectively in the CT-C-F heated-air circulation oven, 60 ± 5 ℃ of dryings 7 hours, cross YK-160 oscillating granulator 20 mesh sieve granulate, add silicon dioxide and magnesium stearate mix homogeneously, the ZP33 rotary tablet machine, the circular recessed stamping of Φ 8.5mm, purchase is from the film coating powder (stomach dissolution type) of Shanghai Colorcon Coating Technology Co., Ltd, join in 30% alcoholic solution of stirring, be made into the suspension of film coating powder (stomach dissolution type) solid content 12%, continue to stir 45 minutes, in the coating process, uninterruptedly stir, coating weightening finish>1.0%, , totally 10000.
Testing result:
Embodiment 4
| Spectinomycin hydrochloride | 1000g |
| Hydroxypropyl methylcellulose K4M | 500g |
| Hydroxypropyl methylcellulose E50 | 200g |
| Lactose | 300g |
| Silicon dioxide | 20g |
| Magnesium stearate | 40g |
| 80% ethanol | 660g |
| 30% ethanol | 227g |
| Film coating powder (stomach dissolution type) | 31g |
Preparation: by spectinomycin hydrochloride, HPMC K4M, in the KJZ-10 Quick-stirring granulator, 5 minutes mix homogeneously of rapid stirring, add 5 minutes soft materials processed of 80% alcoholic solution 220g rapid stirring, YK-160 oscillating granulator 20 mesh sieves are granulated, as medicine-containing particle, by lactose, hypromellose E50 mix homogeneously, 80% alcoholic solution 440g, with the legal system soft material, granulates,, as blank granule, medicine-containing particle and blank granule are respectively in the CT-C-F heated-air circulation oven, 60 ± 5 ℃ of dryings 7 hours, cross YK-160 oscillating granulator 20 mesh sieve granulate, add silicon dioxide and magnesium stearate mix homogeneously, the ZP33 rotary tablet machine, the circular recessed stamping of Φ 8.5mm, purchase is from the film coating powder (stomach dissolution type) of Shanghai Colorcon Coating Technology Co., Ltd, join in 30% alcoholic solution of stirring, be made into the suspension of film coating powder (stomach dissolution type) solid content 12%, continue to stir 45 minutes, in the coating process, uninterruptedly stir, coating weightening finish>1.0%, totally 10000.
Testing result:
Embodiment 5 vitro release tests
Dissolution method: according to dissolution method (two appendix XC the second methods of Chinese Pharmacopoeia version in 2010), the 900mL water of take is dissolution medium, rotating speed is per minute 50 to turn, operation in accordance with the law, sampling in 1 hour, 4 hours, 8 hours, filter respectively, get subsequent filtrate as need testing solution, according to ultraviolet visible spectrophotometry (two appendix IV A of Chinese Pharmacopoeia version in 2010), measure respectively absorbance at the wavelength place of 274nm; Separately get the about 25.0mg of spectinomycin hydrochloride reference substance, accurately weighed, put in the 250mL measuring bottle, be dissolved in water and be diluted to scale, shake up, product solution, be measured in the same method absorbance in contrast, calculates respectively every release at different time.
Each embodiment measurement result sees the following form.
| Embodiment | 1 hour release (%) | 1 hour release (%) | 1 hour release (%) |
| Embodiment 1 | 29.05 | 64.21 | 90.36 |
| Embodiment 2 | 28.05 | 63.21 | 91.36 |
| Embodiment 3 | 29.45 | 63.21 | 90.06 |
| Embodiment 4 | 28.12 | 63.57 | 90.43 |
In the vitro release test, discharged the 25%～45%, 4th hour and discharge release in the 40%～75%, 8th hour more than 75% in first hour.
Claims (10)
1. a metoprolol sustained-release tablet, is characterized in that, described metoprolol sustained-release tablet is grouped into by the one-tenth of following quality proportioning:
Spectinomycin hydrochloride 100, blocker 60～80, filler 20～40, lubricant 2～10, binding agent 50～90, film coating powder 2.5～4.
2. metoprolol sustained-release tablet according to claim 1, is characterized in that, described blocker is selected from one or more in hypromellose K100LV, K100M, K4M, E50 or SH4000.
3. metoprolol sustained-release tablet according to claim 2, is characterized in that, described blocker is selected from HPMC K4M and E50 forms with quality proportioning 1:0.15～0.6.
4. metoprolol sustained-release tablet according to claim 1, is characterized in that, described filler is selected from one or more in lactose, microcrystalline Cellulose, mannitol and starch.
5. metoprolol sustained-release tablet according to claim 4, is characterized in that, described filler is lactose.
6. metoprolol sustained-release tablet according to claim 1, is characterized in that, described lubricant is selected from one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, Polyethylene Glycol or hydrogenated vegetable oil.
7. metoprolol sustained-release tablet according to claim 1, is characterized in that, described lubricant is selected from magnesium stearate and silicon dioxide forms with quality proportioning 1:0.2～2.
8. metoprolol sustained-release tablet, it is characterized in that, described metoprolol sustained-release tablet is grouped into by the one-tenth of following quality proportioning: spectinomycin hydrochloride 100, blocker hydroxypropyl methylcellulose K4M 45, blocker hydroxypropyl methylcellulose E50 25, filler lactose 30, lubricant silicon dioxide 2, magnesium stearate lubricant 4,80% ethanol 66,30% ethanol 22.7, film coating powder 3.1.
9. prepare a kind of method of metoprolol tartrate extended release tablets as claimed in claim 1, it is characterized in that, the method comprises the following steps:
(1) by spectinomycin hydrochloride and a kind of blocker mix homogeneously, add the alcoholic solution of 60%-90%, be preferably 80% alcoholic solution and prepare soft material, cross 20 mesh sieves and make medicine-containing particle;
(2) by filler and another blocker mix homogeneously, add the alcoholic solution of 60%-90%, be preferably 80% alcoholic solution soft material processed, cross 20 mesh sieves and make blank granule;
(3) by medicine-containing particle and the rear mistake 20 mesh sieve granulate of 60 ± 5 ℃ of heated-air circulation oven dryings of blank granule, add magnesium stearate and micropowder silica gel mix homogeneously;
(4) tabletting;
(5) with stomach dissolved film coating pre-mix dose, make coating solution, coating, obtain metoprolol tartrate extended release tablets.
10. the method for preparing the metoprolol sustained-release tablet according to claim 9, it is characterized in that, the coating solution of described step (5), for by stomach dissolution type film coating powder being joined in 30% alcoholic solution of stirring, is mixed with the suspension of stomach dissolution type film coating powder solid content 12%.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103989652A (en) * | 2014-06-03 | 2014-08-20 | 上海信谊百路达药业有限公司 | Metoprolol tartrate sustained-release preparation and preparation method thereof |
| CN105030718A (en) * | 2015-08-18 | 2015-11-11 | 石家庄格瑞药业有限公司 | Arotinolol hydrochloride preparation and preparation method thereof |
| CN105267174A (en) * | 2014-06-30 | 2016-01-27 | 南京瑞尔医药有限公司 | Pharmaceutical composition containing metoprolol tartrate and preparation method of pharmaceutical composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085195A (en) * | 2011-01-10 | 2011-06-08 | 中国药科大学 | Metoprolol succinate sustained-release tablets and preparation method thereof |
-
2013
- 2013-08-21 CN CN2013103682169A patent/CN103405394A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085195A (en) * | 2011-01-10 | 2011-06-08 | 中国药科大学 | Metoprolol succinate sustained-release tablets and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| SUBHASH CHAND DADARWAL ET AL.: "Formulation and evaluation of delayed-onset extended-release tables of metoprolol tartrate using hydrophilic-swellable polymers", 《ACTA PHARM.》, 31 March 2012 (2012-03-31) * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103989652A (en) * | 2014-06-03 | 2014-08-20 | 上海信谊百路达药业有限公司 | Metoprolol tartrate sustained-release preparation and preparation method thereof |
| CN105267174A (en) * | 2014-06-30 | 2016-01-27 | 南京瑞尔医药有限公司 | Pharmaceutical composition containing metoprolol tartrate and preparation method of pharmaceutical composition |
| CN105030718A (en) * | 2015-08-18 | 2015-11-11 | 石家庄格瑞药业有限公司 | Arotinolol hydrochloride preparation and preparation method thereof |
| CN105030718B (en) * | 2015-08-18 | 2018-01-30 | 石家庄格瑞药业有限公司 | A kind of Arotinolol Hydrochlorid preparation and preparation method thereof |
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Application publication date: 20131127 |