CN106606505A - Tofogliflozin pharmaceutical composition and preparation method thereof - Google Patents
Tofogliflozin pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN106606505A CN106606505A CN201510685880.5A CN201510685880A CN106606505A CN 106606505 A CN106606505 A CN 106606505A CN 201510685880 A CN201510685880 A CN 201510685880A CN 106606505 A CN106606505 A CN 106606505A
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- tofogliflozin
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Abstract
The present invention discloses a tofogliflozin pharmaceutical composition and a preparation method thereof, wherein the pharmaceutical composition comprises tofogliflozin, a filler and a disintegrant according to a mass ratio of the tofogliflozin to the filler to the disintegrant of 10:0.5-10:0.5-20, preferably 10:1-5:1-15. According to the present invention, the pharmaceutical composition has characteristics of good fluidity, strong compressibility and less dust, and solves the problems of low dissolution and low bioavailability due to the poor water solubility of the tofogliflozin.
Description
Technical field
The present invention relates to a kind of tofogliflozin pharmaceutical composition and preparation method thereof, belongs to field of pharmaceutical preparations.
Background technology
SLGT2 inhibitor be one kind can specificity suppress glomerule proximal tubule, to filter glucose reabsorption, excessive glucose is discharged from urine, hypoglycemic medicine directly drops.Clinical research shows that SGLT2 inhibitor has good drug effect, safety and toleration, can be effectively reduced blood glucose, becomes a kind of method of new treatment type 2 diabetes mellitus hyperglycemia.
Tofogliflozin is a kind of SLGT2 inhibitor, its in aqueous solution indissoluble, therefore, in order to meet the requirement of clinical biochemical availability, need to increase tofogliflozin dissolubility in an aqueous medium.
Research finds that tofogliflozin if raw material reduces particle diameter by micronization, but because the fusing point of medicine is low, easily produces " tacky phenomenon " before preparation is made, and follow-up crushing is difficult to；If diameter of aspirin particle can be controlled in smaller range, but due to the specific surface area of medicine it is big, drug density is little, it is easily unstable, using 4～8% hydroxypropylcellulose aqueous solution wet granulation when, be also easy to produce the phenomenon of incomplete mixing, cause drug accumulation balling-up, particle diameter increases, and causes the tablet dissolution of preparation not high or diversity between piece and piece is larger.
Therefore, being badly in need of exploitation one kind can improve dissolubility, and the technique of big industrialized production is can be suitably used for again to make preparation.
The content of the invention
In order to overcome the problems referred to above, the present invention to provide a kind of tofogliflozin pharmaceutical composition and preparation method thereof.
The present invention is achieved through the following technical solutions：
A kind of tofogliflozin pharmaceutical composition, containing tofogliflozin, disintegrating agent, filler, wherein tofogliflozin, disintegrating agent, the mass ratio of filler three are 10:(0.5～10):(0.5～20), preferably 10:(1～5):(1～15).
Any one of disintegrating agent in polyvidone, low-substituted hydroxypropyl cellulose, hypromellose in the present invention, or the arbitrarily mixture of two or more compositions.The effect of disintegrating agent be be spray-dried when so that in the composition in the form of high degree of dispersion, its result is the dissolubility that can significantly improve tofogliflozin in pharmaceutical composition to tofogliflozin.
The disintegrating agent of the present invention also has a purpose, can use as adhesive, is played a role by increasing tofogliflozin and the cohesive of filler.
Any one of filler in Lactose, Mannitol, xylitol in the present invention, or the arbitrarily mixture of two or more compositions.Contain multiple hydroxyls in Lactose, three kinds of filling agent molecules of Mannitol and xylitol, be respectively provided with good water solublity.
Particular kind of disintegrating agent, filler and its consumption have been selected in it is critical only that for the present invention so that the pharmaceutical composition release of the present invention is obviously improved.
The preparation method of above-mentioned tofogliflozin pharmaceutical composition, comprises the following steps：
(1) tofogliflozin is dissolved in organic solvent, tofogliflozin：The mass ratio of organic solvent is 1:(5～20)；
(2) disintegrating agent is dissolved in or is dispersed in substantial amounts of aqueous with filler, and solid is 1 with the mass ratio of liquid:(5～20)；
(3) under stirring, the organic liquor of SLGT2 inhibitor in (1) is poured in (2), is persistently stirred 10 minutes～1 hour；
(4) above-mentioned aqueous organic slurry is spray-dried, the temperature for controlling to be spray-dried is 100～120 DEG C；The material after being spray-dried is collected, 60 mesh sieves are crossed, adds moderate lubrication agent, tabletting to obtain tofogliflozin piece.
Organic solvent in the present invention used in step (1) and (2) is any one in acetone, ethanol, isopropanol, or the arbitrarily mixture of two or more compositions.
The beneficial effect that the present invention is produced：
The invention provides a kind of be spray-dried the method for preparing tofogliflozin, the method is to make medicine dissolution in the solution containing disintegrating agent and filler, medicine is fully mixed, and playing improves the synergism of drug release rate.Disintegrating agent prevents the contact between drug molecule in the pharmaceutical composition for being formed.Therefore, the ratio that the present invention passes through regulation three, can reach improves the purpose of tofogliflozin dissolubility, and prepares the granule for doing other dosage forms such as piece agent, granule, capsule.
Specific embodiment
With reference to embodiment, the present invention is further illustrated, but the present invention is not limited to these embodiments.
Embodiment 1
The prescription composition of tofogliflozin piece
Tofogliflozin 100g
Polyvidone 25g
Lactose 20g
Magnesium stearate 5g
Preparation method：Step (1)：Tofogliflozin 100g is taken, ethanol 1500g is added, stirring makes its dissolving or is uniformly dispersed, standby as solution A.
Step (2)：Polyvidone (K30) 25g and Lactose 20g are taken, purified water 500g, stirring so as to dissolve, as solution B is added.
Step (3)：Solution A is added in solution B, is stirred so as to be uniformly dispersed, as solution C.
Step (4)：Solution C is spray-dried in spray dryer, and the temperature for controlling to be spray-dried is 100 DEG C；The material after being spray-dried is collected, 60 mesh sieves are crossed, adds moderate lubrication agent, tabletting to obtain tofogliflozin piece.
Embodiment 2
The prescription composition of tofogliflozin piece
Tofogliflozin 100g
Low-substituted hydroxypropyl cellulose 50g
Mannitol 50g
Magnesium stearate 5g
Preparation method
Step (1)：Tofogliflozin 100g is taken, acetone 700g is added, stirring makes its dissolving or is uniformly dispersed, standby as solution A.
Step (2)：Low-substituted hydroxypropyl cellulose 50g and Mannitol 50g are taken, purified water, stirring so as to dissolve, as solution B is added.
Step (3)：Solution A is added in solution B, is stirred so as to be uniformly dispersed, as solution C.
Step (4)：Solution C is spray-dried in spray dryer, and the temperature for controlling to be spray-dried is 115 DEG C；The material after being spray-dried is collected, 60 mesh sieves are crossed, adds moderate lubrication agent, tabletting to obtain tofogliflozin piece.
Embodiment 3
The prescription composition of tofogliflozin piece
Tofogliflozin 100g
Low-substituted hydroxypropyl cellulose 50g
Xylitol 100g
Magnesium stearate 5g
Preparation method step (1)：Tofogliflozin 100g is taken, ethanol-aqueous isopropanol (2 is added:8, w/w) 1500g, stirring makes its dissolving or is uniformly dispersed, standby as solution A.
Step (2)：Low-substituted hydroxypropyl cellulose 50g and xylitol 100g is taken, aqueous 800g, stirring so as to dissolve, as solution B is added.
Step (3)：Solution A is added in solution B, is stirred so as to be uniformly dispersed, as solution C.
Step (4)：Solution C is spray-dried in spray dryer, and the temperature for controlling to be spray-dried is 105 DEG C；The material after being spray-dried is collected, 60 mesh sieves are crossed, adds moderate lubrication agent, tabletting to obtain tofogliflozin piece.
The stripping curve of experimental example 1 is determined：Tofogliflozin piece in above-described embodiment 1～3 is taken, is adopted《Chinese Pharmacopoeia》(version two in 2010) annex XC dissolution methods are determined in accordance with the law.
Dissolving device：Paddle method；Rotating speed：75rpm；Temperature：37±0.5℃；Dissolution medium：Water (contains 0.75% sodium lauryl sulphate)；Medium volume：600ml；Analysis method：High performance liquid chromatography (HPLC)；Detection wavelength：240nm；Mobile phase：Acetonitrile-water (pH 6.5, H containing 20mM3PO4)(50:50)；Chromatographic column：C18 chromatographic columns (5 μm, 4.6 × 150mm)；Column temperature：40℃；Flow velocity：1ml/min.
As a result show, in tofogliflozin piece medicine when in 5min, dissolution reaches more than 60%, 10min dissolution more than 80%, dissolution illustrates that medicine can rapid dissolution in the aqueous of regulation in granule more than 90% during 15min.
Although the above-mentioned specific embodiment to the present invention is described; but not limiting the scope of the invention; one of ordinary skill in the art should be understood that; on the basis of technical scheme, various modifications that those skilled in the art make by need not paying creative work or deformation are still within protection scope of the present invention.
Claims (6)
1. a kind of tofogliflozin pharmaceutical composition, containing tofogliflozin, disintegrating agent, filler, it is characterised in that tofogliflozin, disintegrating agent, the mass ratio of filler three are 10:0.5～10:0.5～20.
2. pharmaceutical composition according to claim 1, it is characterised in that the tofogliflozin, disintegrating agent, the mass ratio of filler three are 10:1～5:1～15.
3. pharmaceutical composition according to claim 1, it is characterised in that any one of the disintegrating agent in polyvidone, low-substituted hydroxypropyl cellulose, hypromellose, or arbitrarily two or more mixture.
4. pharmaceutical composition according to claim 1, it is characterised in that any one of the filler in Lactose, Mannitol, xylitol, or arbitrarily two or more mixture.
5. according to the preparation method of the arbitrary described pharmaceutical composition of claim 1-4, it is characterised in that comprise the following steps：(1) tofogliflozin is dissolved in organic solvent, and tofogliflozin is 1 with the mass ratio of organic solvent:5～20；(2) disintegrating agent is dissolved in or is dispersed in water with filler, and solid is 1 with the mass ratio of liquid:(5～20), (3) pour the liquid obtained by step (1) in the liquid obtained by step (2) under stirring, persistently stir 10 minutes～1 hour；(4) organic slurry obtained in step (3) is spray-dried, the temperature for controlling to be spray-dried is 100～120 DEG C, collects the material after being spray-dried, and crosses 60 mesh sieves, and tabletting obtains tofogliflozin piece.
6. the preparation method of pharmaceutical composition according to claim 5, it is characterised in that the organic solvent used in the step (1) is any one in acetone, ethanol, isopropanol, or arbitrarily two or more mixture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510685880.5A CN106606505A (en) | 2015-10-22 | 2015-10-22 | Tofogliflozin pharmaceutical composition and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510685880.5A CN106606505A (en) | 2015-10-22 | 2015-10-22 | Tofogliflozin pharmaceutical composition and preparation method thereof |
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| CN106606505A true CN106606505A (en) | 2017-05-03 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107693514A (en) * | 2017-12-04 | 2018-02-16 | 威海贯标信息科技有限公司 | A kind of glug arranges net composition |
| CN107759649A (en) * | 2017-12-12 | 2018-03-06 | 威海贯标信息科技有限公司 | A kind of tofogliflozin novel crystal forms |
| CN107811983A (en) * | 2017-12-04 | 2018-03-20 | 威海贯标信息科技有限公司 | A kind of tofogliflozin composition |
-
2015
- 2015-10-22 CN CN201510685880.5A patent/CN106606505A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107693514A (en) * | 2017-12-04 | 2018-02-16 | 威海贯标信息科技有限公司 | A kind of glug arranges net composition |
| CN107811983A (en) * | 2017-12-04 | 2018-03-20 | 威海贯标信息科技有限公司 | A kind of tofogliflozin composition |
| CN107759649A (en) * | 2017-12-12 | 2018-03-06 | 威海贯标信息科技有限公司 | A kind of tofogliflozin novel crystal forms |
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Application publication date: 20170503 |