CN105796515A - Empagliflozin oral disintegrating tablet and preparation method thereof - Google Patents
Empagliflozin oral disintegrating tablet and preparation method thereof Download PDFInfo
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- CN105796515A CN105796515A CN201410845193.0A CN201410845193A CN105796515A CN 105796515 A CN105796515 A CN 105796515A CN 201410845193 A CN201410845193 A CN 201410845193A CN 105796515 A CN105796515 A CN 105796515A
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- palie
- oral cavity
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Abstract
The invention discloses an empagliflozin oral disintegrating tablet and a preparation method thereof. The empagliflozin oral disintegrating tablet contains empagliflozin as the main drug, the auxiliary materials include lactose, mannitol, croscarmellose sodium, sodium carboxymethyl starch, hydroxy propyl cellulose, magnesium stearate and aspartame, and the empagliflozin oral disintegrating tablet is prepared by direct compression method. The method has the characteristics of simple operation, accurate metering and high bioavailability, and the oral disintegrating tablet prepared by direct compression has high porosity and good permeability. The oral disintegrating tablet disintegrates rapidly after being taken, can be swallowed without water, is free of gritty sense, can disintegrate completely within 40s and can pass through a 80-mesh sieve, and has a dissolution rate up to more than 90% in water and a phosphate buffer solution within 5 minutes. The preparation technology involved in the invention is simple and saves time, and the prepared oral disintegrating tablet has the advantages of smooth surface, complete disintegration and high dissolution rate, and is suitable for industrial production.
Description
Technical field
The present invention relates to the clean field of SGLT2 inhibitor medicaments Yi Palie, relate in particular to clean oral cavity disintegration tablet of Yi Palie and preparation method thereof, belong to pharmaceutical preparation research field.
Background technology
Yi Palie clean (empagliflozin) is the white-2(SCLT2 of a kind of sodium glucose co-transporter 2) inhibitor class medicine, it can block the resorption of glucose in kidney, too much glucose is excreted to external, thus reduce the effect of blood sugar level, and this hypoglycemic effect does not rely on β cell function and insulin resistant.
This medicine be there is no development & production by current China, mainly by external particularly Europe import.
The dosage form of Europe listing is conventional tablet, and by by clean for Yi Palie crude drug and pharmaceutic adjuvant, such as microcrystalline Cellulose, the tabletting after wet granulation such as hydroxypropyl cellulose and magnesium stearate forms.Owing to it needs addition organic solvent or water to granulate in production process, then passing sequentially through the technological processes such as dry, granulate, tabletting again, therefore length consuming time, medicine is easily by air pollution.Meanwhile, in order to obtain better result of extraction, sometimes also need to add secondary granulation step so that whole technique is complicated, consume is big, and cost is high.
Summary of the invention
The present inventor is according to research, it has been found that dosage is excessive first in clinical practice for the conventional tablet of European market listing, and dysphagia, and this brings difficulty to the patient of old man, child and dysphagia, and compliance is poor.Under water deficit conditions, the use of the clean tablet of Yi Palie has been also affected by serious restriction simultaneously.
Therefore, the present inventor attempts to look for a kind of clean dosage form of new A Yipalie, thus overcoming Yi Palie net products in use Problems existing.
In order to realize this purpose, we disclosing a kind of clean oral cavity disintegration tablet of Yi Palie, the clean oral cavity disintegration tablet of described Yi Palie is mainly again the Yi Palie of recipe quantity and only forms with lactose, mannitol, cross-linking sodium carboxymethyl cellulose, Sodium Hydroxymethyl Stalcs, hydroxypropyl cellulose, magnesium stearate and aspartame.
Further, we prefer that wherein each ingredients weight parts is lactose 1 ~ 50 part, 1 ~ 50 part of mannitol, cross-linking sodium carboxymethyl cellulose 1 ~ 40 part, carboxymethyl starch sodium 0.5 ~ 60 part, hydroxypropyl cellulose 1 ~ 10 part, magnesium stearate 0.01 ~ 5 part, aspartame 0.01 ~ 5 part.
It is further preferable that we also disclosed each ingredients weight parts is lactose 15 ~ 45 parts, 10 ~ 30 parts of mannitol, cross-linking sodium carboxymethyl cellulose 15 ~ 24 parts, carboxymethyl starch sodium 5 ~ 30 parts, hydroxypropyl cellulose 3 ~ 5 parts, magnesium stearate 0.5 ~ 1 part, aspartame 1.5 ~ 3 parts.
Meanwhile, the preparation method that we further disclose the clean oral cavity disintegration tablet of a kind of Yi Palie in the present invention, comprise the following steps:
(1) lactose of recipe quantity, mannitol, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose, aspartame are directly mixed with equivalent method of progressively increasing, obtain mixture A；
(2) clean for the Yi Palie of recipe quantity crude drug is uniformly blended in mixture A with the equivalent method of progressively increasing, obtains mixture B；
(3) magnesium stearate is added in mixture B, mixing, tabletting.
Wherein the Yi Palie of recipe quantity accounts for total amount 22 ~ 28 parts, lactose 1 ~ 50 part, 1 ~ 50 part of mannitol, cross-linking sodium carboxymethyl cellulose 1 ~ 40 part, carboxymethyl starch sodium 0.5 ~ 60 part, hydroxypropyl cellulose 1 ~ 10 part, magnesium stearate 0.01 ~ 5 part, aspartame 0.01 ~ 5 part only.
Preferably, lactose 15 ~ 45 parts, 10 ~ 30 parts of mannitol, cross-linking sodium carboxymethyl cellulose 15 ~ 24 parts, carboxymethyl starch sodium 5 ~ 30 parts, hydroxypropyl cellulose 3 ~ 5 parts, magnesium stearate 0.5 ~ 1 part, aspartame 1.5 ~ 3 parts.
Further, we disclose described preparation temperature is 10 DEG C ~ 30 DEG C, it is preferable that this temperature is 15 ~ 28 DEG C.
As the preferred tabletting mode of one, we prefer that openly described tabletting adopts direct powder compression tabletting.
The clean oral cavity disintegration tablet smooth surface morphology of Yi Palie disclosed in this invention, can complete disintegrate in 40 seconds, disintegrate thing all can pass through 80 mesh sieves, and the clean oral cavity disintegration tablet of Yi Palie disclosed in this invention 5 minutes dissolutions in water/phosphate buffered solution reach more than 90% simultaneously.Compared to Europe listing the clean sheet of Yi Palie its have speed collapse, the feature such as instant, rapid-action.
Preparation method disclosed in this invention consuming time short, technique is simple, operation is few, it is not necessary to special installation, special monitoring and special monitoring, be suitable for industrialized production.Preparation method labor cost disclosed in this invention is low simultaneously, and product quality is high, and industrial applications prospect is good.
Detailed description of the invention
For being further appreciated by the present invention, below in conjunction with implementing technical scheme disclosed in this invention is described in detail, protection scope of the present invention is not limited by the following examples.
Experimental technique described in following example, if no special instructions, is conventional method, involved reagent and material, if no special instructions, is the commercially available prod of commercial sources.
Embodiment 1:
The clean 25g of raw material prescription: Yi Palie
Mannitol 25g
Lactose 42g
Cross-linking sodium carboxymethyl cellulose 16g
Carboxymethyl starch sodium 10g
Hydroxypropyl cellulose 4g
Magnesium stearate 0.785g
Aspartame 2.215g
Make 100
Preparation technology: by recipe quantity lactose, mannitol, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose and aspartame with equivalent progressively increase method mixing, progressively increase clean for the Yi Palie of recipe quantity method mixing with equivalent with the above-mentioned powder mixed again, it is eventually adding the magnesium stearate mixing of recipe quantity, determine tablet weight and hardness, direct compression, the i.e. clean oral cavity disintegration tablet of get Yi Palie.Whole preparation technology completes at 20 DEG C.
Outward appearance: the clean oral cavity disintegration tablet of Yi Palie prepared by this law is off-white color, smooth surface morphology.
Disintegration: take the clean oral cavity disintegration tablet of prepared Yi Palie 1, be placed in 2ml pure water, under 37 DEG C of conditions, whole disintegrates in 40 seconds also pass through 80 mesh sieves.
Dissolution: taking the clean oral cavity disintegration tablet of Ben Yipalie 6 with water for dissolution medium, the dissolution of 5 minutes is 94.67%.Separately taking the clean oral cavity disintegration tablet of Ben Yipalie 6 with phosphate buffer solution for dissolution medium (Chinese Pharmacopoeia two annex Ⅹ C the second methods of version in 2010), the dissolution of 5 minutes is 93.82%.
Embodiment 2:
The clean 25g of raw material prescription: Yi Palie
Mannitol 25g
Lactose 42g
Cross-linking sodium carboxymethyl cellulose 15g
Carboxymethyl starch sodium 11g
Hydroxypropyl cellulose 4g
Magnesium stearate 0.785g
Aspartame 2.215g
Make 100
Preparation technology: by recipe quantity lactose, mannitol, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose and aspartame with equivalent progressively increase method mixing, progressively increase clean for the Yi Palie of recipe quantity method mixing with equivalent with the above-mentioned powder mixed again, it is eventually adding the magnesium stearate mixing of recipe quantity, determine tablet weight and hardness, direct compression, the i.e. clean oral cavity disintegration tablet of get Yi Palie.Whole preparation technology completes at 20 DEG C.
Outward appearance: the clean oral cavity disintegration tablet of Yi Palie prepared by this law is off-white color, smooth surface morphology.
Disintegration: take the clean oral cavity disintegration tablet of prepared Yi Palie 1, be placed in 2ml pure water, under 37 DEG C of conditions, whole disintegrates in 40 seconds also pass through 80 mesh sieves.
Dissolution: taking the clean oral cavity disintegration tablet of Ben Yipalie 6 with water for dissolution medium, the dissolution of 5 minutes is 95.89%.Separately taking the clean oral cavity disintegration tablet of Ben Yipalie 6 with phosphate buffer solution for dissolution medium (Chinese Pharmacopoeia two annex Ⅹ C the second methods of version in 2010), the dissolution of 5 minutes is 93.56%.
Embodiment 3:
The clean 25g of raw material prescription: Yi Palie
Mannitol 25g
Lactose 42g
Cross-linking sodium carboxymethyl cellulose 17g
Carboxymethyl starch sodium 9g
Hydroxypropyl cellulose 4g
Magnesium stearate 0.785g
Aspartame 2.215g
Make 100
Preparation technology: by recipe quantity lactose, mannitol, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose and aspartame with equivalent progressively increase method mixing, progressively increase clean for the Yi Palie of recipe quantity method mixing with equivalent with the above-mentioned powder mixed again, it is eventually adding the magnesium stearate mixing of recipe quantity, determine tablet weight and hardness, direct compression, the i.e. clean oral cavity disintegration tablet of get Yi Palie.Whole preparation technology completes at 20 DEG C.
Outward appearance: the clean oral cavity disintegration tablet of Yi Palie prepared by this law is off-white color, smooth surface morphology.
Disintegration: take the clean oral cavity disintegration tablet of prepared Yi Palie 1, be placed in 2ml pure water, under 37 DEG C of conditions, whole disintegrates in 40 seconds also pass through 80 mesh sieves.
Dissolution: taking the clean oral cavity disintegration tablet of Ben Yipalie 6 with water for dissolution medium, the dissolution of 5 minutes is 95.91%.Separately taking the clean oral cavity disintegration tablet of Ben Yipalie 6 with phosphate buffer solution for dissolution medium (Chinese Pharmacopoeia two annex Ⅹ C the second methods of version in 2010), the dissolution of 5 minutes is 92.17%.
Embodiment 4
The clean oral cavity disintegration tablet stability study of Yi Palie
(1) test specimen: the clean oral cavity disintegration tablet of Yi Palie (lot number: 140707) of the embodiment of the present invention 1 preparation.
(2) carrying out factors influencing according to " chemicals stability study technological guidance's principle ", test sample is respectively at 60 DEG C, and RH95 ± 5%, when 4500 ± 500Lx, placement 10 days, in 0,5,10 day taking sample determination, compared with 0 day, and result is in Table 1.
The clean oral cavity disintegration tablet study on the stability result of table 1 Yi Palie
(3) being accelerated experiment investigation according to " chemicals stability study technological guidance's principle ", test sample is packaged in temperature 40 ± 2 DEG C by simulation listing, places when the constant temperature and humidity of relative humidity RH75 ± 5%, respectively at 0,1,2, sampling product examine in 3,6 months is looked into, and result is in Table 2.
The clean oral cavity disintegration tablet accelerated test of table 2 Yi Palie investigates result
Embodiment 5
The clean oral cavity disintegration tablet of Yi Palie and the Europe import Yi Palie clean tablet contrast test to blood glucose and body weight
Take 50 wister male rats, body weight is 180-220g, it is randomly divided into 5 groups by body weight, often group 10, it is divided into blank group, the clean oral cavity disintegration tablet low dosage of Yi Palie, high dose, the clean sheet low dosage of Yi Palie, high dose group, before administration, Rat Fast can't help water 16h, according to 1.0ml/100g body weight, distilled water is given by blank group, administration group gives tested medicine, at 30min, 60min and 180min is in tail vein blood, measure SerumGlu value, calculate each group of blood glucose meansigma methods and standard deviation, and compare with blank group respectively, carry out t inspection, observe the body weight change of rat simultaneously, result is in Table 3, 4.
The clean oral cavity disintegration tablet of table 3 Yi Palie and the Europe import Yi Palie clean tablet impact (X ± D) on normal rat blood sugar
Note: compare * * P < 0.01 with blank group
The clean oral cavity disintegration tablet of table 4 Yi Palie and the Europe import Yi Palie clean tablet impact on normal rat body weight
The clean oral cavity disintegration tablet of result: Yi Palie and the clean sheet of Yi Palie all can significantly reduce rat blood sugar value, compare with blank group and have pole significant difference (P < 0.01), the clean oral cavity disintegration tablet of Yi Palie and the clean sheet of Yi Palie and all can reduce rat body weight.
Claims (7)
1. the clean oral cavity disintegration tablet of Yi Zhong Yi Palie, it is characterized in that, the clean oral cavity disintegration tablet of described Yi Palie is mainly made up of with lactose, mannitol, cross-linking sodium carboxymethyl cellulose, Sodium Hydroxymethyl Stalcs, hydroxypropyl cellulose, magnesium stearate and aspartame only the Yi Palie of recipe quantity.
2. the clean oral cavity disintegration tablet of Yi Palie according to claim 1, it is characterized in that: each ingredients weight parts is lactose 1 ~ 50 part, 1 ~ 50 part of mannitol, cross-linking sodium carboxymethyl cellulose 1 ~ 40 part, carboxymethyl starch sodium 0.5 ~ 60 part, hydroxypropyl cellulose 1 ~ 10 part, magnesium stearate 0.01 ~ 5 part, aspartame 0.01 ~ 5 part.
3. the clean oral cavity disintegration tablet of Yi Palie according to claim 2, it is characterized in that: each ingredients weight parts is lactose 15 ~ 45 parts, 10 ~ 30 parts of mannitol, cross-linking sodium carboxymethyl cellulose 15 ~ 24 parts, carboxymethyl starch sodium 5 ~ 30 parts, hydroxypropyl cellulose 3 ~ 5 parts, magnesium stearate 0.5 ~ 1 part, aspartame 1.5 ~ 3 parts.
4. the preparation method of the clean oral cavity disintegration tablet of Yi Palie described in any one in a claim 1 ~ 3, it is characterised in that comprise the following steps:
(1) lactose of recipe quantity, mannitol, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl cellulose, aspartame are directly mixed with equivalent method of progressively increasing, obtain mixture A；
(2) clean for the Yi Palie of recipe quantity crude drug is uniformly blended in mixture A with the equivalent method of progressively increasing, obtains mixture B；
(3) magnesium stearate is added in mixture B, mixing, tabletting.
5. the preparation method of the clean oral cavity disintegration tablet of Yi Palie according to claim 4, it is characterised in that: described preparation temperature is 10 DEG C ~ 30 DEG C.
6. the preparation method of the clean oral cavity disintegration tablet of Yi Palie according to claim 5, it is characterised in that: described preparation temperature is 15 ~ 28 DEG C.
7. the preparation method of the clean oral cavity disintegration tablet of Yi Palie according to claim 5, it is characterised in that: direct powder compression tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410845193.0A CN105796515A (en) | 2014-12-31 | 2014-12-31 | Empagliflozin oral disintegrating tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410845193.0A CN105796515A (en) | 2014-12-31 | 2014-12-31 | Empagliflozin oral disintegrating tablet and preparation method thereof |
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| CN105796515A true CN105796515A (en) | 2016-07-27 |
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| CN201410845193.0A Pending CN105796515A (en) | 2014-12-31 | 2014-12-31 | Empagliflozin oral disintegrating tablet and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112618495A (en) * | 2020-12-29 | 2021-04-09 | 青岛黄海制药有限责任公司 | Empagliflozin dry suspension and preparation method thereof |
| WO2024005755A1 (en) * | 2022-06-29 | 2024-01-04 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A tablet comprising empagliflozin |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1726916A (en) * | 2004-07-27 | 2006-02-01 | 江西省药物研究所 | Oral disintegration tablet for dropping blood sugar and preparation method |
| CN102387783A (en) * | 2009-02-13 | 2012-03-21 | 贝林格尔.英格海姆国际有限公司 | Pharmaceutical composition comprising glucopyranosyl diphenylmethane derivatives, pharmaceutical dosage form thereof, process for their preparation and uses thereof for improved glycemic control in a patient |
| CN102499907A (en) * | 2011-11-02 | 2012-06-20 | 华裕(无锡)制药有限公司 | Orally disintegrating tablet composition |
-
2014
- 2014-12-31 CN CN201410845193.0A patent/CN105796515A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1726916A (en) * | 2004-07-27 | 2006-02-01 | 江西省药物研究所 | Oral disintegration tablet for dropping blood sugar and preparation method |
| CN102387783A (en) * | 2009-02-13 | 2012-03-21 | 贝林格尔.英格海姆国际有限公司 | Pharmaceutical composition comprising glucopyranosyl diphenylmethane derivatives, pharmaceutical dosage form thereof, process for their preparation and uses thereof for improved glycemic control in a patient |
| CN102499907A (en) * | 2011-11-02 | 2012-06-20 | 华裕(无锡)制药有限公司 | Orally disintegrating tablet composition |
Non-Patent Citations (3)
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| 姚静编: "《药用辅料应用指南》", 31 August 2011, 中国医药科技出版社 * |
| 潘卫三主编: "《工业药剂学（第二版）》", 30 June 2010, 中国医药科技出版社 * |
| 郭慧玲等主编: "《药剂学》", 30 April 1996, 人民卫生出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112618495A (en) * | 2020-12-29 | 2021-04-09 | 青岛黄海制药有限责任公司 | Empagliflozin dry suspension and preparation method thereof |
| CN112618495B (en) * | 2020-12-29 | 2022-06-14 | 青岛黄海制药有限责任公司 | Empagliflozin dry suspension and preparation method thereof |
| WO2024005755A1 (en) * | 2022-06-29 | 2024-01-04 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A tablet comprising empagliflozin |
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Application publication date: 20160727 |
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