Dry granulation process of sitagliptin phosphate composition

A dry granulation technology of sitagliptin phosphate, which is applied to drug combinations, medical preparations containing no active ingredients, medical preparations containing active ingredients, etc., can solve the problems of delayed disintegration time and impurities of sitagliptin phosphate Exceeding the standard, delamination and other problems to achieve the effect of improving stability and disintegration speed

Active Publication Date: 2022-08-09
宁波高新区美诺华医药创新研究院有限公司
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  • Abstract
  • Description
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AI Technical Summary

Problems solved by technology

However, the main degradation pathway of sitagliptin phosphate is hydrolysis. Therefore, the use of wet granulation will cause a small amount of API degradation and cause stability risks. In addition, wet granulation has the disadvantage of complex process
[0004] However, the direct tableting method tends to cause delamination of the ingredients, and the dry granulation method tends to cause sticking to the rollers. The sitagliptin phosphate prepared by both methods has excessive impurities and delayed disintegration time, which cannot meet the requirements.

Method used

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  • Dry granulation process of sitagliptin phosphate composition

Examples

Experimental program
Comparison scheme
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preparation example Construction

[0017] Wherein the preparation method of tablet, coating is as follows:

[0018] Tabletting: put the granules prepared by this process into the hopper of the tablet press and press them into tablets.

[0019] Coating: Add purified water to the container, slowly add the film coating premix under constant stirring, and stir for at least 45 minutes. Then control the inlet air temperature, main engine speed and inlet air volume, the tablet bed temperature is 42-50°C, the atomization pressure is 0.2-0.4MPa, and the spraying speed is 5-100rpm (depending on the spraying test) for spray coating.

[0020] More preferably, before spraying the liquid, preheat first, and start spraying when the temperature of the tablet bed reaches 42°C. When the weight increases to 2-4%, stop spraying, dry and cool.

[0021] The film-coating premix adopts the common stomach-dissolving film-coating dosage form on the market.

[0022] The API of sitagliptin phosphate has needle-like and rod-like crystal...

Embodiment 1

[0024] 1) Premix, add microcrystalline cellulose, sitagliptin phosphate and anhydrous calcium hydrogen phosphate into the mixing hopper, mix at 15 rpm for 5 minutes, then pass the mixture through a 30-mesh sieve, and then add croscarmellose The plain sodium and sodium stearyl fumarate were passed through a 30-mesh sieve, and then put into the mixing hopper for mixing, and mixed at 15 rpm for 12 min.

[0025] 2) Dry granulation machine, adjust the rotation speed of the pressing roller, the gap of the pressing roller is 0.4-0.5mm, the hydraulic pressure is 3MPa, the crushing speed is 80rpm, the pre-granulation speed is 100rpm, and the final granulation speed is 100rpm. The above and the mixture are dry granulated . The ribbons obtained by granulation are firstly passed through a 2.0mm screen at a suitable speed, and then pulverized by passing through a 1.0mm screen.

[0026] 3) Mixing: Add the dry granulation material into the mixing hopper and mix at 15 rpm for 5 minutes.

[...

Embodiment 2

[0032] 1) Premix, add microcrystalline cellulose, sitagliptin phosphate and anhydrous calcium hydrogen phosphate into the mixing hopper, mix at 15rpm for 10min, then pass the mixture through a 30-mesh sieve, and then add croscarmellose The plain sodium and sodium stearyl fumarate were passed through a 30-mesh sieve, and then put into the mixing hopper for mixing, and mixed at 15 rpm for 15 minutes.

[0033] 2) Dry granulator granulation, adjust the speed of the pressing roller, the gap of the pressing roller is 0.4-0.5mm, the hydraulic pressure is 3.5MPa, the crushing speed is 85rpm, the pre-granulation speed is 105rpm, and the final granulation speed is 100rpm. grain. The ribbons obtained by granulation are firstly passed through a 2.0mm screen at a suitable speed, and then pulverized by passing through a 1.0mm screen.

[0034] 3) Mixing: Add the dry granulated material into the mixing hopper and mix at 15 rpm for 6 minutes.

[0035] Total mixing: manually pass magnesium st...

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Abstract

The invention discloses a dry granulation process for a sitagliptin phosphate composition, which includes the following steps: 1) selecting a phosphate liptin bulk drug with needle-like or rod-like shape; 2) premixing microcrystalline cellulose, west phosphate Gliptin and anhydrous calcium hydrogen phosphate are mixed and sieved, and then sieved croscarmellose sodium and sodium stearyl fumarate are added for blending; 3) granulation, and the final step in step 2). The mixture is prepared into granules by a dry granulator; 4) The material obtained from granulation is mixed with the sieved magnesium stearate. The needle-like or rod-like crystal habit has a larger specific surface area and is more prone to API inconsistencies. In a stable situation, with the addition of sodium stearyl fumarate in the granules, it is beneficial to accelerate the disintegration rate of the tablet. After the dry granules are prepared, most of sitagliptin phosphate has been wrapped in the dry granules, and then When mixed with magnesium stearate, the contact area between API and magnesium stearate is greatly reduced, ensuring the stability of the finished product.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a dry granulation process for a sitagliptin phosphate composition. Background technique [0002] Sitagliptin Phosphate is a DPP-IV inhibitor for type 2 diabetes. The drug can improve the decrease in insulin secretion in the pathogenesis of type 2 diabetes by strengthening the incretin axis; by reducing the level of glucagon, it can inhibit the Hepatic glucose overproduction provides new avenues for the treatment of patients with type 2 diabetes. However, the disadvantage is that sitagliptin phosphate tablets have insufficient stability, and when placed under certain conditions, such as high temperature and / or high humidity, impurities are easily generated, resulting in the prepared pharmaceutical composition failing to meet the storage period requirements. [0003] At present, wet granulation is often used for sitagliptin preparations to improve the powder pr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/12A61K47/38A61K9/28A61K31/4985A61P3/10
CPCA61K9/1682A61K9/1617A61K9/1652A61K9/28A61K31/4985A61P3/10
Inventor 姚振江苏尼尔·库马尔·潘达汪宜俊叶连挺王春艳戴勋仁曹倩王飞云
Owner 宁波高新区美诺华医药创新研究院有限公司
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