CN105641706A - Mirabegron medicine composition and preparation method thereof - Google Patents

Abstract

The invention discloses a mirabegron medicine composition. A recipe comprises framework materials; and 20 weight percent to 25 weight percent of mannitol and 10 weight percent to 20 weight percent of microcrystalline cellulose are used as filling agents. The mirabegron medicine composition has the beneficial effects that the stability is high; and the obvious advantages are realized on product yield improvement, cost reduction, industrialization realization and good clinical application.

Description

A kind of Mirabegron pharmaceutical composition and its preparation method

Technical field

The invention belongs to medical art, it is specifically related to Mirabegron pharmaceutical composition and its preparation method.

Background technology

Mirabegron (Mirabegron) is a kind of selectivity ��3-adrenergicreceptor agonist, is mainly used in treatment grownup's overactive bladder on clinical. Its chemistry is by name: (R)-2-(2-amino-1,3-thiazole-4-base)-4'-[2-[(2-hydroxyl-2-styroyl) amino] ethyl] phenylacetamide, and structural formula is as follows:

Mirabegron tablet is developed by Ben Ansi Old Taylor (Astel-las) drugmaker, list on September 16th, 2011 in Japan, on June 28th, 2012, FDA approval was used for the treatment of grownup's overactive bladder (OAB), and commodity are called Myrbetriq.

Merariveron sustained-release tablet can lower the impact that it is absorbed by food, and before or after meals all can be taken, and can maintain the effective blood drug concentration of long-time stable, is that curative effect of medication increases so that within one day, only needing a slice, patient compliance increases.

But, with reference to oral preparations not only complex process prepared by existing method, production cost height, it is difficult to realize the big production of industrialization, and slow release instability, fluctuation is big, and preparation is unstable, the problems such as the easy moisture absorption. Still new method is needed to prepare Merariveron sustained-release tablet at present. The applicant finds through research, and the key in fact preparing Merariveron sustained-release tablet is to find the ratio of suitable auxiliary material and various auxiliary material, good fluidity when ensureing compressing tablet, and result of extraction is good, and finished product is stablized.

The present inventor is through the research to prior art, and unexpected discovery, applies special auxiliary material, Mirabegron pharmaceutical composition prepared by special process, and reliable in quality, is easy to industrialization, reduces production cost, is easy to implement, remarkable in economical benefits.

Summary of the invention

For overcoming in prior art the shortcoming existing for Mirabegron preparation, one aspect of the present invention provides a kind of pharmaceutical composition containing Mirabegron, and said composition formula is simple, mature preparation process.

2nd object of the present invention is to provide the preparation method of Mirabegron pharmaceutical composition of the present invention, and the method is simple, and prepared Mirabegron pharmaceutical composition, steady quality is reliable.

For realizing first object of the present invention, the present inventor surprisingly finds the pharmaceutical composition of a kind of Mirabegron, containing framework material, adopts N.F,USP MANNITOL and Microcrystalline Cellulose as weighting agent in said composition prescription, its consumption N.F,USP MANNITOL 20%-25% by weight percentage, Microcrystalline Cellulose 10%-20%.

The pharmaceutical composition of the present invention also comprises auxiliary material or the additive that one or more are pharmaceutically commonly used, such as lubricant, glidant etc., wherein framework material be selected from Vltra tears, Xylo-Mucine, ethyl cellulose one or more;Lubricant is selected from Magnesium Stearate or talcum powder, and glidant is selected from micropowder silica gel.

Mirabegron pharmaceutical composition, by weight percentage, concrete composition is as follows:

Mirabegron 10-20%

Framework material 30-50%

N.F,USP MANNITOL 20-25%

Microcrystalline Cellulose 10-20%

Lubricant 1-3%

Glidant 0.5-2%

Preferably,

Mirabegron 10%

Framework material 50%

N.F,USP MANNITOL 25%

Microcrystalline Cellulose 10%

Lubricant 3%

Glidant 2%

The weight percent content 20-25% of N.F,USP MANNITOL in above-mentioned composition, the particle diameter of N.F,USP MANNITOL is preferably 50% particle diameter lower than 150 ��m, after adopting such particle diameter can better with other auxiliary materials particularly Microcrystalline Cellulose mix, thus play filling effect better.

Preferably, in above-mentioned composition, the content of the weight percent of Microcrystalline Cellulose is 10-20%, owing to the addition of Microcrystalline Cellulose in the present invention as auxiliary weighting agent, the consumption of N.F,USP MANNITOL is reduced, thus reduce the cost of whole prescription, overcome the tablet friability of gained that is excessive due to N.F,USP MANNITOL consumption and that cause higher, it is not suitable for the shortcoming of shipping storage and use.

N.F,USP MANNITOL and Microcrystalline Cellulose are mixed as weighting agent, the existing correlation technique about Merariveron sustained-release tablet also has no relevant report.

Mirabegron pharmaceutical composition of the present invention is adopted and is prepared with the following method, and the method comprises the steps:

1) Mirabegron, framework material, N.F,USP MANNITOL and Microcrystalline Cellulose were pulverized respectively 100 order sieves, for subsequent use;

2) take the above-mentioned materials of recipe quantity, with 10% PVP K30 ethanol solution softwood, granulate with 20 screen clothes;

3) at the temperature of 50 �� 2 DEG C, air seasoning 2-3 hour in loft drier;

4) add lubricant and glidant, mix with dry particle;

5) calculate the actual sheet weight of gained, regulate sheet weight, compressing tablet;

6) film coating agent of recipe quantity being mixed with content as the solution of 10% taking 70% ethanol, carry out dressing, inlet temperature is 40 DEG C, coating liquid spray speed 10ml/min;

7) requirement according to product is packed, and puts in storage after packaging.

On the basis of existing pharmaceutical adjunct and preparation technology, the present inventor finds through a large amount of experimental studies, and Mirabegron pharmaceutical composition is above-mentioned formula and during preparation technology, and described pharmaceutical composition quality is effectively ensured.

Compared with prior art, tool of the present invention has the following advantages:

1) Mirabegron pharmaceutical composition provided by the present invention is for improving the receipts rate of this product, reduce products production cost, and being better applied to clinical treatment has very big help.

2) new Mirabegron composition provided by the present invention, through industrialized production and study on the stability, proves constant product quality.

3) preparation method of new Mirabegron composition provided by the present invention, the method is simple, prepared Mirabegron pharmaceutical composition reliable in quality.

Embodiment

Following examples are only for explaining the present invention, and are not used in restriction the present invention. Unless otherwise indicated, the experiment condition in the embodiment of the present invention is the experiment condition of this area routine.

Embodiment 1

Mirabegron pharmaceutical composition described in every 1000, its formula consists of:

Mirabegron 25g

Vltra tears 125g

N.F,USP MANNITOL 62.5g

Microcrystalline Cellulose 20g

Magnesium Stearate 7.5g

Micropowder silica gel 5g

Preparation technology: 1) Mirabegron, Vltra tears, N.F,USP MANNITOL and Microcrystalline Cellulose were pulverized respectively 100 order sieves, for subsequent use;

2) take the above-mentioned materials of recipe quantity, with 10% PVP K30 ethanol solution softwood, granulate with 20 screen clothes;

3) at the temperature of 50 �� 2 DEG C, air seasoning 2-3 hour in loft drier;

4) add Magnesium Stearate and micropowder silica gel, mix with dry particle;

5) calculate the actual sheet weight of gained, regulate sheet weight, compressing tablet;

6) film coating agent of recipe quantity being mixed with content as the solution of 10% taking 70% ethanol, carry out dressing, inlet temperature is 40 DEG C, coating liquid spray speed 10ml/min;

7) requirement according to product is packed, and puts in storage after packaging.

Embodiment 2

Mirabegron pharmaceutical composition described in every 1000, its formula consists of:

Mirabegron 50g

Ethyl cellulose 133.3g

N.F,USP MANNITOL 66.7g

Microcrystalline Cellulose 66.7g

Magnesium Stearate 10g

Micropowder silica gel 6.7g

Preparation technology: 1) Mirabegron, ethyl cellulose, N.F,USP MANNITOL and Microcrystalline Cellulose were pulverized respectively 100 order sieves, for subsequent use;

2) take the above-mentioned materials of recipe quantity, with 10% PVP K30 ethanol solution softwood, granulate with 20 screen clothes;

3) at the temperature of 50 �� 2 DEG C, air seasoning 2-3 hour in loft drier;

4) add Magnesium Stearate and micropowder silica gel, mix with dry particle;

5) calculate the actual sheet weight of gained, regulate sheet weight, compressing tablet;

6) film coating agent of recipe quantity being mixed with content as the solution of 10% taking 70% ethanol, carry out dressing, inlet temperature is 40 DEG C, coating liquid spray speed 10ml/min;

7) requirement according to product is packed, and puts in storage after packaging.

Test example 1

Sample thief, places respectively at high temperature 60 DEG C, RH92.5% and intensity of illumination 4500Lx �� 500Lx when, respectively at sampling in 5 days, 10 days, detection, and compares with 0 day, and experimental result sees the following form.

This Mirabegron pharmaceutical composition has good stability and dissolution rate under the environment of high temperature, high wet and illumination.

Release detects

Adopt Chinese Pharmacopoeia 2010 editions annex XC dissolution method the 2nd method (slurry processes) 75rpm. Using the stripping release profiles of the tablet that the Ph4.5 acetate buffer 900mL containing 0.2%SDS is prepared as dissolution medium, the detection embodiment of the present invention 1 and embodiment 2, result is as follows:

Claims (6)

1. a Mirabegron pharmaceutical composition, containing framework material, it is characterised in that adopt N.F,USP MANNITOL and Microcrystalline Cellulose as weighting agent, its consumption N.F,USP MANNITOL 20%-25% by weight percentage, Microcrystalline Cellulose 10%-20%.

2. Mirabegron pharmaceutical composition according to claim 1, it is characterised in that: by weight percentage, concrete composition is as follows:

Mirabegron 10-20%

Framework material 30-50%

N.F,USP MANNITOL 20-25%

Microcrystalline Cellulose 10-20%

Lubricant 1-3%

Glidant 0.5-2%.

3. Mirabegron pharmaceutical composition according to claim 2, it is characterised in that: by weight percentage, concrete composition is as follows:

Mirabegron 10%

Framework material 50%

N.F,USP MANNITOL 25%

Microcrystalline Cellulose 10%

Lubricant 3%

Glidant 2%.

4. Mirabegron pharmaceutical composition according to the arbitrary item of claims 1 to 3, it is characterised in that described framework material be selected from Vltra tears, Xylo-Mucine, ethyl cellulose one or more.

5. Mirabegron pharmaceutical composition according to the arbitrary item of claim 2 to 3, it is characterised in that described lubricant is selected from Magnesium Stearate or talcum powder, and glidant is selected from micropowder silica gel.

6. the preparation method of Mirabegron pharmaceutical composition described in the arbitrary item of claim 1-5, it is characterised in that:

1) Mirabegron, framework material, N.F,USP MANNITOL and Microcrystalline Cellulose were pulverized respectively 100 order sieves, for subsequent use;

2) take the above-mentioned materials of recipe quantity, with 10% PVP K30 ethanol solution softwood, granulate with 20 screen clothes;

3) at the temperature of 50 �� 2 DEG C, air seasoning 2-3 hour in loft drier;

4) add lubricant and glidant, mix with dry particle;

5) calculate the actual sheet weight of gained, regulate sheet weight, compressing tablet;

6) film coating agent of recipe quantity being mixed with content as the solution of 10% taking 70% ethanol, carry out dressing, inlet temperature is 40 DEG C, coating liquid spray speed 10ml/min;

7) requirement according to product is packed, and puts in storage after packaging.