CN106606489A - Canagliflozin tablets and preparation method thereof - Google Patents
Canagliflozin tablets and preparation method thereof Download PDFInfo
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- CN106606489A CN106606489A CN201510686747.1A CN201510686747A CN106606489A CN 106606489 A CN106606489 A CN 106606489A CN 201510686747 A CN201510686747 A CN 201510686747A CN 106606489 A CN106606489 A CN 106606489A
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- canagliflozin
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Abstract
The invention discloses a canagliflozin pharmaceutical composition and a preparation process thereof. The canagliflozin pharmaceutical composition comprises canagliflozin and a carrier material, wherein the carrier material is povidone. The canagliflozin tablets disclosed by the invention have the characteristics of being fast to dissolve out and simple in preparation process.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of pharmaceutical preparation, more particularly to a kind of tablet containing canagliflozin and preparation method thereof.
Background technology
Canagliflozin (canagliflozin) is by a kind of sodium-glucose co-transport body 2 of the pharmacy of Johnson ＆ Johnson of the U.S. and day Honda side Rhizoma Sparganii pharmacy joint development
(SGLT-2) inhibitor；For improving the glycemic control of type Ⅱdiabetes mellitus adult patient, type 2 diabetes mellitus blood glucose level in patients can be effectively reduced, and safety is higher, obtained FDA and EMEA at present and ratified the treatment for type Ⅱdiabetes mellitus.
Canagliflozin Selective depression SGLT2 can suppress most of glucose reabsorption in vivo, promote glucose to discharge from urine in a large number and reach the purpose for controlling blood sugar level.Extra blood sugar reducing function can be provided as unrelated with insulin therefore any with other the treating diabetes scheme of the mechanism of action of canagliflozin (including insulin) is used in combination.Both can combine with other oral antidiabetic drug for poor blood glucose control under existing therapeutic scheme or insulin resistant problem patient, the patient that the very low and existing oral drugs of β cell functions cannot be acted on can be used for insulin combination again.
Canagliflozin poorly water-soluble, the dissolution in vitro for how improving preparation are the key points for affecting its curative effect.
The present inventor is by research and puts into practice pleasantly surprised discovery：Selecting the carrier being adapted to prepare canagliflozin becomes solid dispersion, can solve an above-mentioned difficult problem.
The content of the invention
It is an object of the invention to provide a kind of canagliflozin piece and its preparation technology, in the tablet, raw material and can guarantee that the quick release of medicine without the need for micronization processes without addition surfactant.
A kind of canagliflozin pharmaceutical composition, containing canagliflozin, carrier material and pharmaceutically can be suitable pharmaceutic adjuvant.
The carrier material is polyvidone.
In the present invention, canagliflozin and the weight ratio of carrier material are 1:4-6, preferably 1:5.
On Chinese materia medica of the present invention, acceptable adjuvant is filler, disintegrating agent, lubricant, wherein, filler is Lactose, Microcrystalline Cellulose, Mannitol, one or more in pregelatinized Starch；Disintegrating agent is Croscarmellose Sodium, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, one or more in polyvinylpolypyrrolidone；Lubricant is magnesium stearate, sodium stearyl fumarate, one or more in silicon dioxide.
It is Mannitol and Microcrystalline Cellulose to be preferably filled with agent, and disintegrating agent is Croscarmellose Sodium, and lubricant is magnesium stearate.
Weight ratio shared by each composition of pharmaceutical composition of the present invention is：
(a) canagliflozin 5%～20%；
(b) polyvidone 15%～60%；
(c) Mannitol 10%～30%；
(d) Microcrystalline Cellulose 10%～30%；
(e) Croscarmellose Sodium 1%～10%；
(f) magnesium stearate 5%～15%.
Preferably, shared by each composition, weight ratio is：
(a) canagliflozin 5～15%；
(b) polyvidone 15%～50%；
(c) Mannitol 15%～25%；
(d) Microcrystalline Cellulose 15%～25%；
(e) Croscarmellose Sodium 1%～10%；
(f) magnesium stearate 5%～15%.
Another object of the present invention is to provide a kind of method for preparing aforementioned pharmaceutical compositions, the method is comprised the following steps：
(1) will stir to being completely dissolved during canagliflozin and carrier material add solvent；
(2) remove solvent and dry, pulverize to obtain solid dispersion；
(3) solid dispersion for preparing (2) is mixed with other pharmaceutically acceptable adjuvants, tabletting.
Wherein, one or more of the solvent selected from methanol that uses in step 1, ethanol, acetone, chloroform, dichloromethane, preferred alcohol.
Remove in step 2 the method for organic solvent selected from removing under reduced pressure, drying under reduced pressure, vacuum drying, lyophilization, spray drying, fluid bed drying, heating, drying, preferred drying under reduced pressure.
Canagliflozin piece according to the present invention has dissolution rapid, the advantage of preparation process is simple.
Specific embodiment
Following embodiments are used to the present invention to be explained further, it is not intended that the scope of the present invention is only limitted to following examples.
Embodiment 1
Ingredient Wt percentage ratio
Canagliflozin 10%
Polyvidone 40%
Mannitol 20%
Microcrystalline Cellulose 20%
Croscarmellose Sodium 8%
Magnesium stearate 2%
Preparation technology：
(1) polyvidone is added in ethanol, is stirred to being completely dissolved, add canagliflozin to stir to dissolving, it is standby；
(2) solution for preparing (1), stirs, and 60 DEG C are dried removal solvent, cross 60 mesh sieves, obtain canagliflozin solid dispersion；
(3) solid dispersion for preparing (2) is mixed homogeneously with Mannitol, Microcrystalline Cellulose, cross-linked carboxymethyl cellulose, sieves, and adds magnesium stearate mix homogeneously, and the shallow arc stampings of Φ 10mm control 50～80N of hardness.
Embodiment 2
Ingredient Wt percentage ratio
Canagliflozin 10%
Polyvidone 50%
Mannitol 20%
Microcrystalline Cellulose 15%
Croscarmellose Sodium 4%
1% preparation method of magnesium stearate is with embodiment 1.
Embodiment 3
Ingredient Wt percentage ratio
Canagliflozin 5%
Polyvidone 30%
Mannitol 25%
Microcrystalline Cellulose 25%
Croscarmellose Sodium 10%
5% preparation method of magnesium stearate is with embodiment 1.
Comparative example 1
Canagliflozin 10%
Polyvidone 40%
Mannitol 20%
Microcrystalline Cellulose 20%
Croscarmellose Sodium 8%
Magnesium stearate 2%
Preparation method：Canagliflozin is mixed homogeneously with polyvidone, is added dehydrated alcohol granulation, is dried, granulation adds Mannitol, Microcrystalline Cellulose, Croscarmellose Sodium and magnesium stearate mix homogeneously, tabletting.
Comparative example 2
Canagliflozin 10%
Polyvidone 30%
Mannitol 25%
Microcrystalline Cellulose 25%
Croscarmellose Sodium 8%
Magnesium stearate 2%
Preparation method is with embodiment 1.
Experimental example 1
The dissolution determination of canagliflozin piece
Chromatographic condition：It is filler with octadecylsilane chemically bonded silica, pH6.5- acetonitriles (40 (is adjusted with 0.02% phosphate buffer：60) it is mobile phase, flow velocity 1ml/min, Detection wavelength are 254nm.Take this product, according to dissolution method (Chinese Pharmacopoeia version annex the second methods of XC in 2010), phosphate buffer (containing 0.5% sodium lauryl sulphate) 900ml with pH6.8 is as solvent, rotating speed is 75 turns per minute, operate in accordance with the law, when 5,10,15,30,45min, take solution 5ml, filtration, takes subsequent filtrate as need testing solution；Canagliflozin reference substance about 10mg is taken separately, it is accurately weighed, put in 100ml measuring bottles, plus a small amount of EtOH Sonicate makes dissolving, scale is diluted to dissolution fluid.Shake up, as reference substance solution.Precision measures need testing solution and each 20 μ l of reference substance solution inject chromatograph of liquid, records chromatogram, by external standard method with calculated by peak area, obtains final product.Measurement result see the table below：
Canagliflozin piece dissolution determination result (%)
Embodiment 5min 10min 15min 30min 45min
Embodiment 1 63.6 85.7 96.6 99.5 99.8
Embodiment 2 68.2 87.3 98.9 100.1 100.0
Embodiment 3 59.9 83.9 94.8 98.7 99.6
Comparative example 1 29.4 45.3 71.2 80.8 92.7
Comparative example 2 39.5 50.3 75.6 83.9 93.5
As can be known from the above table, the dissolution of embodiment 1-3 is fast, and 15min is close to complete dissolution.Comparative example 1-2 fails complete dissolution in 60min.It can be seen that, by choosing specific preparation technology, while the ratio of canagliflozin and polyvidone is controlled, in certain scope, to improve the dissolution of medicine.
Experimental example 2
By embodiment 1-3 and comparative example 1-2 1 month under the conditions of 30 DEG C/60%RH in about material contrast
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Comparative example 1 | Comparative example 2 | |
| 0 day | 0.36 | 0.35 | 0.36 | 0.35 | 0.35 |
| 30 days | 0.37 | 0.36 | 0.37 | 0.87 | 0.47 |
As can be known from the above table, there is good chemical stability during the pharmaceutical composition that prepared by present invention storage under acceleration conditions.
Claims (9)
1. a kind of canagliflozin pharmaceutical composition, it is characterised in that containing canagliflozin, carrier material and pharmaceutically can be suitable pharmaceutic adjuvant.
2. pharmaceutical composition according to claim 1, it is characterised in that canagliflozin is 1 with the weight ratio of carrier material:4-6.
3. pharmaceutical composition according to claim 3, it is characterised in that canagliflozin is 1 with the weight ratio of carrier material:5.
4. the pharmaceutical composition according to any one of claim 1-4, it is characterised in that described carrier material is selected from polyvidone.
5. pharmaceutical composition according to claim 1, it is characterised in that pharmaceutically acceptable adjuvant is filler, disintegrating agent, lubricant, wherein, filler be Lactose, Microcrystalline Cellulose, Mannitol, in pregelatinized Starch
One or more；Disintegrating agent is Croscarmellose Sodium, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, one or more in polyvinylpolypyrrolidone；Lubricant is magnesium stearate, sodium stearyl fumarate, one or more in silicon dioxide.
6. pharmaceutical composition according to claim 6, which is made up of canagliflozin, polyvidone, Mannitol, Microcrystalline Cellulose, Croscarmellose Sodium, magnesium stearate.
7. pharmaceutical composition according to claim 7, wherein weight ratio is shared by each composition：
(a) canagliflozin 5%～20%；
(b) polyvidone 15%～60%；
(c) Mannitol 10%～30%；
(d) Microcrystalline Cellulose 10%～30%；
(e) Croscarmellose Sodium 1%～10%；
(f) magnesium stearate 5%～15%.
8. a kind of preparation method of the pharmaceutical composition as described in any one of claim 1-7, it is characterised in that the method is comprised the following steps：
(1) will stir to being completely dissolved during canagliflozin and carrier material add solvent；
(2) remove solvent and dry, pulverize to obtain solid dispersion；
(3) solid dispersion for preparing (2) is mixed with other pharmaceutically acceptable adjuvants, tabletting.
9. the preparation method of pharmaceutical composition according to claim 8, it is characterised in that one or more in the solvent selected from methanol, ethanol, acetone, chloroform, dichloromethane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510686747.1A CN106606489A (en) | 2015-10-22 | 2015-10-22 | Canagliflozin tablets and preparation method thereof |
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| CN201510686747.1A CN106606489A (en) | 2015-10-22 | 2015-10-22 | Canagliflozin tablets and preparation method thereof |
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| CN106606489A true CN106606489A (en) | 2017-05-03 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078945A (en) * | 2018-01-12 | 2018-05-29 | 杭州中美华东制药有限公司 | Canagliflozin pharmaceutical composition |
| CN112043675A (en) * | 2020-08-27 | 2020-12-08 | 蚌埠丰原涂山制药有限公司 | Canagliflozin solid dispersion and Canagliflozin solid preparation containing same |
-
2015
- 2015-10-22 CN CN201510686747.1A patent/CN106606489A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078945A (en) * | 2018-01-12 | 2018-05-29 | 杭州中美华东制药有限公司 | Canagliflozin pharmaceutical composition |
| CN108078945B (en) * | 2018-01-12 | 2020-09-11 | 杭州中美华东制药有限公司 | Canagliflozin pharmaceutical composition |
| CN112043675A (en) * | 2020-08-27 | 2020-12-08 | 蚌埠丰原涂山制药有限公司 | Canagliflozin solid dispersion and Canagliflozin solid preparation containing same |
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Application publication date: 20170503 |
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