CN104288117A - Tablet composition with solubilizing and slow release effects - Google Patents
Tablet composition with solubilizing and slow release effects Download PDFInfo
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- CN104288117A CN104288117A CN201410479288.5A CN201410479288A CN104288117A CN 104288117 A CN104288117 A CN 104288117A CN 201410479288 A CN201410479288 A CN 201410479288A CN 104288117 A CN104288117 A CN 104288117A
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- mirabegron
- solubilizing agent
- framework material
- solubilising
- lubricant
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Abstract
The invention relates to the technical field of medicines, in particular relates to a tablet composition with solubilizing and slow release effects and a preparation method thereof and particularly relates to mirabegron sustained release tablets. The preparation method comprises the following steps: mixing proper medical auxiliary materials comprising a framework material, a solubilizer and a filling agent with mirabegron, and preparing a mirabegron pharmaceutical preparation which is fully and slowly released. The tablet composition is suitable for single dose and has the service characteristic of lasting slow and full release.
Description
Technical field
The present invention relates to medical art, is specifically related to tablet composition with solubilising slow releasing function and preparation method thereof, adopts suitable pharmaceutic adjuvant and Mirabegron to combine, and makes Mirabegron pharmaceutical preparation that is abundant, slow releasing.
Background technology
Insoluble drug medicine due to poorly soluble and cause bioavailability unstable, need special adjuvant in addition solubilising; The treatment of some disease, sometimes need the effect that medicine low dosage continues, transient high blood drug level is disadvantageous to patient sometimes.The existence of above two kinds of factors, what be has slow release thing is called the needs of clinical treatment and the sky of solubilising is taken medicine.
Such as: overactive bladder (Overactive Bladder, the syndrome of feature that OAB) to be a kind of with symptoms of urgency be (comprises various diseases, as Female Urethral Syndrome, the young and middle-aged unknown cause frequent micturition of male etc.), normal with frequent micturition and nocturia, can accompany or not accompany urge incontinence; Urodynamics can show as overactive detrusor and cause frequent micturition, frequent micturition is a kind of main suit, refers to that patient urinates conscious every day too frequent.On the basis of subjective sensation, number of micturitions reaches: in the daytime >=8 times, night >=2 times time be thought of as frequent micturition.Nocturia refers to that patient is more than the main suit revived because urinating more than 1 time/night.The treatment of frequent micturition, namely needs the low dosage continuous action of medicine.
Mirabegron (mirabegron), is used for the treatment of adult's overactive bladder.Mirabegron is a β 3 adrenoceptor agonists class medicine being used for the treatment of overactive bladder.The medicine of overactive bladder also comprises choline m receptor antagonist, as tolterodine, song department chloramines, YM-905, has the side effect such as xerostomia, constipation.Mirabegron is by exciting beta 3 adrenoreceptor, and lax bladder muscle, improves bladder capacity, reduces the symptoms such as the enuresis, urgent micturition, frequent micturition, without cholinergic side effect.But too high Mirabegron concentration, has blood pressure to raise untoward reaction.
Mirabegron is made the slow releasing preparation of fully release, be conducive to avoiding side effect blood pressure to raise the generation of untoward reaction, and be conducive to maintaining the effect that long stable blood drug level effectively reaches its continuative improvement frequent micturition.
Summary of the invention
The object of this invention is to provide a kind of Merariveron sustained-release tablet.Before or after meals all can be taken, and is conducive to maintaining the effect that long stable blood drug level effectively reaches its continuative improvement frequent micturition.The present invention provides a kind of preparation method of Merariveron sustained-release tablet simultaneously.
Technical scheme of the present invention:
There is the tablet composition of solubilising slow releasing function:
Raw material primarily of following weight proportion is made:
Framework material 50mg-500mg,
Corrosion filler 10mg-500mg,
Solubilizing agent 5mg-50mg
Lubricant 2mg ~ 20mg
Binding agent is appropriate.
Described filling framework material is selected: hypromellose; Erodible filler is selected from: PEG300 or lactose,
Solubilizing agent is selected from: polyglyceryl fatty acid ester, Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate.
The present invention also provides a kind of tablet composition with solubilising slow releasing function to make primarily of the raw material of following weight proportion:
Mirabegron 25mg,
Framework material 50mg-500mg,
Filler 10mg-500mg,
Solubilizing agent 5mg-50mg
Lubricant 2mg ~ 20mg
Binding agent is appropriate.
Described Mirabegron is crude drug, or the unformed intermediate to be made up of crude drug, the unformed intermediate of described Mirabegron, get Mirabegron crude drug, being placed in enough methanol with waiting polyvinylpyrrolidone (PVK-30) of weight portion, fully stirring, getting supernatant, 50 DEG C of conditions are little, rotate obtained by evaporate to dryness methanol.
Described framework material refers to the mixture of low viscosity to high viscosity hypromellose, and binding agent is that binder dosage is every 1000 consumptions is 0 ~ 150ml containing the alcoholic solution of 1% ~ 5% ethyl cellulose or the alcoholic solution of 3% ~ 10% polyvinylpyrrolidone.
Except framework material, also have solubilizing agent and corrosion filler; Wherein solubilizing agent is selected from and is: polyglyceryl fatty acid ester, Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate; Corrosion filler; Be selected from: a kind of, two or more the compositions of Liquid Macrogol, PEG400, polyoxyethylene 12 hydroxyl stearic acid ester, lactose.
The preparation method of Merariveron sustained-release tablet of the present invention is:
A preparation method for Merariveron sustained-release tablet, primarily of following weight proportion raw material, make by step successively:
A) in 1000:
Mirabegron 25g,
Framework material 50g-500g,
Corrosion filler 10g-500g,
Solubilizing agent 5g-50g
Lubricant 2g ~ 20g
Binding agent 25 ~ 150ml.
B) by equivalent method of progressively increasing, Mirabegron is mixed homogeneously with framework material, solubilizing agent, corrosion filler, with 2.5% ethyl cellulose 95% alcoholic solution, the powder after above-mentioned mix homogeneously is made soft material, cross 16 mesh sieves to granulate, in 55 ~ 60 DEG C of aeration-dryings, control water content <3%, after 14 mesh sieve granulate, add the lubricant of recipe quantity, mixing, tabletting.
A preparation method for Merariveron sustained-release tablet, primarily of following weight proportion raw material, make by step successively:
A) in 1000:
Mirabegron 25g,
Framework material 50g-500g,
Corrosion filler 10g-500g,
Solubilizing agent 5g-50g
Lubricant 2g ~ 20g
Binding agent 25 ~ 150ml.
B) Mirabegron mixed homogeneously with framework material, solubilizing agent, corrosion filler by equivalent method of progressively increasing, briquetting, pulverizing, cross 16-40 mesh sieve and granulate, after 20 mesh sieve granulate, add the lubricant of recipe quantity, mixing, tabletting.
The preparation method of a kind of Merariveron sustained-release tablet of the present invention, controls tablet hardness between 5.5 ~ 8.0kg.
Technique effect
There is the tablet composition consumption proportion screening of solubilising slow releasing function:
Rule of thumb accessory formula according to the form below to be examined or check is numbered, make tablet respectively, investigate the every quality index of tablet and release by Chinese Pharmacopoeia.
Compared by release curve, the prescription of tested number 6 is more excellent.
In often kind of scheme, Mirabegron is 25g
Merariveron sustained-release tablet initial prescription is screened:
Mirabegron hydrophilic gel matrix sustained release tablet adjuvant screens: rule of thumb numbered by accessory formula according to the form below to be examined or check, make tablet respectively, investigate every quality index and release by Chinese Pharmacopoeia, carry out the prescription screening of this product, the results are shown in following table.
Result shows, and select HPMC as slow-release material, using PEG300 as corrosion filler, this product, as cosolvent, is made erodible matrix sustained release tablet by Butylated hydroxyanisole, and Mirabegron can reach fully release slowly.
Result shows that prescription 6 release meets Formulation requirement, selects prescription 6 as the basic prescription composition of this product.
Mirabegron secondary prescription release characteristics the selection result:
Secondary visit the selection result shows that prescription 3 release meets Formulation requirement substantially.
Technique effect illustrates:
Because part insoluble medicine needs permanent release onset time, short period release may cause the side effect of the abnormal drug such as blood pressure, heart rate, therefore, needs exploitation can have the additive of tablet compositions of slow release hydrotropy.
Technical solution of the present invention is a kind of erodible matrix; Wherein hypromellose its be hydrophilic gel matrix material, make slow releasing tablet with it and meet after gastro-intestinal Fluid, absorb water slightly swelling, formation gel barrier and control drug-eluting.Be then the key factor affecting drug release in vitro with bulk erosion for insoluble drug, due to gel layer progressive additive, rate of releasing drug is slowed down gradually, drug release of the present invention is comparatively uniform and stable.
Find in the present invention's research, the release of simple hydrogel matrix hypromellose to general insoluble drug has retardation, only has and selects appropriate cosolvent and corrosion filler, could produce the releasing effect of satisfying the demand.
Slow releasing tablet adjuvant is except hydrophilic gel matrix material hypromellose, and still the multiple corrosion filler of multiselect combinationally uses, conventional as lactose and amylum pregelatinisatum.
The present invention uses PEG300, and technological process is simple and direct, is conducive to controlling cost.
Method for making of the present invention is convenient, controls tablet hardness between 5.5 ~ 8kg, very convenient in production working control.
Embodiment
Embodiment 1
1000 Merariveron sustained-release tablet, every sheet is containing Mirabegron 25mg.
Mirabegron 25g,
Hypromellose 250g,
PEG300 50g，
Butylated hydroxyanisole 10g
Magnesium stearate 2g ~ 20g
Binding agent 25 ~ 150ml.
Method for making: progressively increase method by Mirabegron and framework material hypromellose, corrosion filler by equivalent: PEG300, Butylated hydroxyanisole etc. are fully mixed homogeneously by above-mentioned weight portion, powder after above-mentioned mix homogeneously is made soft material by every 500g 2.5% ethyl cellulose 95% alcoholic solution 80ml, cross 20 mesh sieves to granulate, in 55 ~ 60 DEG C of aeration-dryings, control water content <3%, after 14 mesh sieve granulate, add the magnesium stearate 5g of recipe quantity, mixing, tabletting.
Embodiment 2
1000 Merariveron sustained-release tablet, every sheet is containing Mirabegron 25mg.
Mirabegron 25g,
Hypromellose 300g,
PEG300-lactose 120g,
Butylated hydroxyanisole 20g
Magnesium stearate 20g
Binding agent 25 ~ 150ml.
Method for making: Mirabegron and framework material hypromellose, the corrosion filler mixture of 1:1 (PEG300 and the lactose by weight), Butylated hydroxyanisole etc. are mixed homogeneously by equivalent method of progressively increasing, with 60ml95% alcoholic solution, ethyl cellulose is mixed with the solution of 2.5%, powder after above-mentioned mix homogeneously is made soft material, cross 26 mesh sieves to granulate, in 55 ~ 60 DEG C of aeration-dryings, control water content <3%, after 14 mesh sieve granulate, add the magnesium stearate of recipe quantity, mixing, tabletting, controls tablet hardness between 7.5kg.
Embodiment 3
1000 Merariveron sustained-release tablet, every sheet is containing Mirabegron 25mg.
Mirabegron 25g,
Hypromellose 500g,
PEG300-lactose 10g,
Butylated hydroxyanisole 35g
Magnesium stearate 2g ~ 20g
Binding agent 25 ~ 150ml.
The wherein corrosion filler mixture of 3:1 (PEG300 and the lactose by weight).
Embodiment 4
1000 Merariveron sustained-release tablet, every sheet is containing Mirabegron 25mg.
Mirabegron 25g,
Hypromellose 500g,
PEG300-lactose 10g,
Butylated hydroxyanisole 35g
Magnesium stearate 2g ~ 20g
Binding agent 25 ~ 150ml.
The wherein corrosion filler mixture of 5:1 (PEG300 and the lactose by weight).
Embodiment 6
1000 Merariveron sustained-release tablet, every sheet is containing Mirabegron 25mg.
Mirabegron 25g,
Hypromellose 250g,
PEG300 50g，
Butylated hydroxyanisole 10g
Magnesium stearate 2g ~ 20g
Binding agent 25 ~ 150ml.
Method for making: with embodiment 1.
Measure vitro release, be no less than 20% by the release in 4 hours of Chinese Pharmacopoeia method and be not more than 35%.Release in 6 hours is no less than 35%, is not more than 55%.Release in 12 hours is no less than 60.07%, is not more than 75%.
Embodiment 7
1000 Merariveron sustained-release tablet, every sheet is containing Mirabegron 25mg.
Mirabegron intermediate is equivalent to Mirabegron 25mg,
Framework material 50mg-500mg,
Corrosion filler 10mg-500mg,
Solubilizing agent 5mg-50mg
Lubricant 2mg ~ 20mg
Binding agent 25 ~ 150ml;
Described Mirabegron intermediate gets Mirabegron crude drug, and be placed in enough methanol with waiting PVK-30 of weight portion, fully stir, get supernatant, 50 DEG C of conditions are little, rotate obtained by evaporate to dryness methanol.
Method for making: with embodiment 1.
Claims (10)
1. there is the tablet composition of solubilising slow releasing function, it is characterized in that: the raw material primarily of following weight proportion is made:
Fill framework material 50mg-500mg,
Corrosion filler 10mg-500mg,
Solubilizing agent 5mg-50mg,
Lubricant 2mg ~ 20mg
Described filling framework material is selected: hypromellose; Erodible filler is selected from: PEG300 or lactose, and solubilizing agent is selected from: polyglyceryl fatty acid ester, Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate.
2. the tablet composition with solubilising slow releasing function according to claim 1, is characterized in that: the raw material primarily of following weight proportion is made:
Mirabegron 25mg,
Fill framework material 50mg-500mg,
Corrosion filler 10mg-500mg,
Solubilizing agent 5mg-50mg,
Lubricant 2mg ~ 20mg.
3. the tablet composition with solubilising slow releasing function according to claim 1 and 2, is characterized in that: the raw material primarily of following weight proportion is made:
Mirabegron intermediate is equivalent to Mirabegron 25mg,
Fill framework material 50mg-500mg,
Corrosion filler 10mg-500mg,
Solubilizing agent 5mg-50mg,
Lubricant 2mg ~ 20mg
Binding agent 25 ~ 150ml;
Described Mirabegron intermediate gets Mirabegron crude drug, and be placed in enough methanol with waiting PVK-30 of weight portion, fully stir, get supernatant, 50 DEG C of conditions are little, rotate obtained by evaporate to dryness methanol.
4. the tablet composition with solubilising slow releasing function according to claim 2, it is characterized in that: described filling framework material refers to the mixture of low viscosity to high viscosity hypromellose, binding agent is that binder dosage is every 1000 consumptions is 0 ~ 150ml containing the alcoholic solution of 1% ~ 5% ethyl cellulose or the alcoholic solution of 3% ~ 10% polyvinylpyrrolidone.
5. the tablet composition with solubilising slow releasing function according to claim 2, is characterized in that: except filling framework material, also have solubilizing agent and corrosion filler.
6. the tablet composition with solubilising slow releasing function according to claim 4, is characterized in that: wherein solubilizing agent is selected from and is: polyglyceryl fatty acid ester, Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate.
7. the tablet composition with solubilising slow releasing function according to claim 4, is characterized in that: corrosion filler is selected from: a kind of, two or more the compositions of Liquid Macrogol, PEG400, polyoxyethylene 12 hydroxyl stearic acid ester, lactose.
8. a kind of Merariveron sustained-release tablet according to claim 1 or 2 or 3, is characterized in that: primarily of following weight proportion raw material, make by step successively:
In 1000:
Mirabegron 25g,
Fill framework material 50g-500g,
Corrosion filler 10g-500g,
Solubilizing agent 5g-50g,
Lubricant 2g ~ 20g
Binding agent 25 ~ 150ml;
By equivalent method of progressively increasing, Mirabegron is mixed homogeneously with framework material, solubilizing agent, corrosion filler, with 2.5% ethyl cellulose 95% alcoholic solution, the powder after above-mentioned mix homogeneously is made soft material, cross 16 mesh sieves to granulate, in 55 ~ 60 DEG C of aeration-dryings, control water content <3%, after 14 mesh sieve granulate, add the lubricant of recipe quantity, mixing, tabletting.
9. a kind of Merariveron sustained-release tablet according to claim 1 or 2 or 3, is characterized in that: primarily of following weight proportion raw material, make by step successively:
In 1000:
Mirabegron 25g,
Fill framework material 50g-500g,
Corrosion filler 10g-500g,
Solubilizing agent 5g-50g
Lubricant 2g ~ 20g
Binding agent 25 ~ 150ml;
Mirabegron mixed homogeneously with framework material, solubilizing agent, corrosion filler by equivalent method of progressively increasing, briquetting, pulverizing, cross 16-40 mesh sieve and granulate, after 20 mesh sieve granulate, add the lubricant of recipe quantity, mixing, tabletting.
10. a kind of Merariveron sustained-release tablet according to claim 4 or 5, is characterized in that: control tablet hardness between 5.5 ~ 8.0kg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410479288.5A CN104288117A (en) | 2014-09-19 | 2014-09-19 | Tablet composition with solubilizing and slow release effects |
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| CN201410479288.5A CN104288117A (en) | 2014-09-19 | 2014-09-19 | Tablet composition with solubilizing and slow release effects |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106361715A (en) * | 2016-09-02 | 2017-02-01 | 迪沙药业集团有限公司 | Mirabegron composition |
| JP2017048136A (en) * | 2015-09-01 | 2017-03-09 | 沢井製薬株式会社 | Mirabegron-containing tablet, manufacturing method of mirabegron-containing pharmaceutical preparation, and manufacturing method of mirabegron-containing granulated product |
-
2014
- 2014-09-19 CN CN201410479288.5A patent/CN104288117A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017048136A (en) * | 2015-09-01 | 2017-03-09 | 沢井製薬株式会社 | Mirabegron-containing tablet, manufacturing method of mirabegron-containing pharmaceutical preparation, and manufacturing method of mirabegron-containing granulated product |
| EP3345600A4 (en) * | 2015-09-01 | 2019-04-10 | Sawai Pharmaceutical Co., Ltd. | Mirabegron-containing tablet, method for producing mirabegron-containing pharmaceutical preparation and method for producing mirabegron-containing granulated product |
| US10925861B2 (en) | 2015-09-01 | 2021-02-23 | Sawai Pharmaceutical Co., Ltd. | Mirabegron-containing tablet, method for producing mirabegron-containing pharmaceutical preparation, and method for producing mirabegron-containing granulated product |
| CN106361715A (en) * | 2016-09-02 | 2017-02-01 | 迪沙药业集团有限公司 | Mirabegron composition |
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