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WO2024037221A1 - Procédé de mesure de la dimension des particules d'agent pharmaceutique actif de dapagliflozine - Google Patents

Procédé de mesure de la dimension des particules d'agent pharmaceutique actif de dapagliflozine Download PDF

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Publication number
WO2024037221A1
WO2024037221A1 PCT/CN2023/104365 CN2023104365W WO2024037221A1 WO 2024037221 A1 WO2024037221 A1 WO 2024037221A1 CN 2023104365 W CN2023104365 W CN 2023104365W WO 2024037221 A1 WO2024037221 A1 WO 2024037221A1
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WO
WIPO (PCT)
Prior art keywords
particle size
dapagliflozin
raw material
sample
size analyzer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2023/104365
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English (en)
Chinese (zh)
Inventor
杨丽丽
陆余钦
王燕飞
李玲玲
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yangtze River Pharmaceutical Group Shanghai Haini Pharmaceutical Co Ltd
Original Assignee
Yangtze River Pharmaceutical Group Shanghai Haini Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yangtze River Pharmaceutical Group Shanghai Haini Pharmaceutical Co Ltd filed Critical Yangtze River Pharmaceutical Group Shanghai Haini Pharmaceutical Co Ltd
Publication of WO2024037221A1 publication Critical patent/WO2024037221A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0205—Investigating particle size or size distribution by optical means
    • G01N15/0211—Investigating a scatter or diffraction pattern

Definitions

  • the present application relates to the technical field of pharmaceutical analysis, and in particular to a method for measuring the particle size of dapagliflozin raw material.
  • Dapagliflozin is the world's first sodium-glucose co-transporter2 (SGLT2) inhibitor to be marketed. It was jointly developed by Bristol-Myers Squibb Company of the United States and AstraZeneca Company of Sweden. In November 2012, Dapagliflozin tablets were approved by EMA as a new antidiabetic drug for the treatment of type 2 diabetes (T2DM). In January 2014, they were approved by the US FDA. In March 2017, they were approved for sale in China. In March 2021, an indication for the treatment of heart failure was added.
  • SGLT2 sodium-glucose co-transporter2
  • dapagliflozin propylene glycol monohydrate whose chemical name is (1S)-1,5-anhydride-1-C-[4-chloro-3-[(4-ethoxyphenyl) Methyl]phenyl]-D-glucitol and (2S)-1,2-propanediol hydrate (1:1:1), the molecular structure is:
  • Dapagliflozin propylene glycol monohydrate is a white to off-white powder that is not hygroscopic and easily soluble in methanol.
  • the API has obvious agglomeration, so it needs to be crushed before production. In order to ensure the consistency of the particle size of the API contained in preparation batches, the particle size of the crushed API needs to be measured.
  • this application provides a particle size determination method for dapagliflozin API with good repeatability and high intermediate precision.
  • This application provides a method for measuring the particle size of dapagliflozin API, which includes the following steps:
  • the particle size analyzer is a laser particle size analyzer
  • the hopper gap is 1.2mm ⁇ 1.8mm
  • the dispersion air pressure is 2bar ⁇ 3.5bar
  • the sample injector used for the sample injection is a dry sample injector, the sample injection volume is 220 mg to 350 mg, and the sample injection speed is 25% to 35%.
  • the measurement time of the particle size analyzer is 8s to 14s.
  • the measurement time of the particle size analyzer is 10 seconds.
  • the injection amount is 300 mg.
  • the injection rate is 30%.
  • the dispersion gas pressure is 3.5 bar.
  • the dispersion gas pressure is 2.5 bar.
  • the hopper gap is 1.5 mm.
  • the dry sampler is an Areo S dry sampler.
  • the laser particle size analyzer is a Malvern Mastersizer3000 laser particle size analyzer.
  • the dapagliflozin API is dapagliflozin propylene glycol monohydrate.
  • the above-mentioned particle size determination method of dapagliflozin API is based on the combination of laser particle size analyzer and dry sampling, and comprehensive parameters such as injection volume, hopper gap, injection speed, dispersion pressure, etc. After optimization, a measurement method with good repeatability and high intermediate precision was obtained, which complies with the control requirements of the Pharmacopoeia for the determination of particle size of raw materials.
  • this method is simple and easy to operate, avoiding complex operations such as solution preparation in wet particle size determination methods.
  • This operation can effectively improve the efficiency of R&D and production, ensure the uniformity of dapagliflozin preparations, and provide reliable quality control technical means for the research of dapagliflozin preparations.
  • the particle size determination method of the dapagliflozin API of the present application will be further described in detail below with reference to specific examples.
  • the application may be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that a thorough understanding of this disclosure will be provided.
  • the above numerical interval is considered to be continuous and includes the minimum value and maximum value of the range, as well as every value between such minimum value and maximum value. Further, when a range refers to an integer, every integer between the minimum value and the maximum value of the range is included. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges can be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to include any and all subranges subsumed therein.
  • the percentage content involved in this application refers to mass percentage for solid-liquid mixing and solid-solid phase mixing, and refers to volume percentage for liquid-liquid phase mixing.
  • the percentage concentrations mentioned in this application refer to the final concentration unless otherwise specified.
  • the final concentration refers to the proportion of the added component in the system after adding the component.
  • the temperature parameters in this application allow for constant temperature treatment or treatment within a certain temperature range.
  • the thermostatic treatment described allows the temperature to fluctuate within the accuracy of the instrument control.
  • the particle size in this application refers to the size of the particles, also known as “particle size” or “diameter”.
  • particle size refers to the size of the particles, also known as “particle size” or “diameter”.
  • D90 particle size refers to the equivalent diameter of the largest particle when the cumulative distribution in the particle size distribution curve is 90%. Its physical meaning is that the particle size is small. Its particles account for 90%; D50 particle size refers to the equivalent diameter of the largest particle when the cumulative distribution in the particle size distribution curve is 50%.
  • D10 particle size refers to The equivalent diameter of the largest particle when the cumulative distribution in the particle size distribution curve is 10%, its physical meaning is that 10% of the particles have a particle size smaller than it.
  • This application provides a method for measuring the particle size of dapagliflozin API, which includes the following steps:
  • the particle size analyzer is a laser particle size analyzer
  • the hopper gap is 1.2mm ⁇ 1.8mm
  • the dispersion air pressure is 2bar ⁇ 3.5bar
  • the injector used for sample injection is a dry method injector, the injection volume is 220 mg ⁇ 350 mg, and the injection speed is 25% ⁇ 35%.
  • the injection amount is a range formed by 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg or any two of the above values as endpoints.
  • the injection amount is 260 mg to 340 mg. Further, the injection amount is 280-320 mg. Furthermore, the injection volume is 300 mg.
  • the injection rate is 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35% or any two of the above values as endpoints. range.
  • the injection rate is 26% to 34%. Further, the sample injection speed is 28% to 32%. Furthermore, the injection speed is 30%.
  • the measurement time of the particle size analyzer is 8s to 14s.
  • the measurement time is a range formed by 8s, 9s, 10s, 11s, 12s, 13s, 14s or any two of the above values as endpoints.
  • the measurement time is 9s to 13s. Further, the measurement time is 10s.
  • the dispersion air pressure is 2.0bar, 2.1bar, 2.2bar, 2.3bar, 2.4bar, 2.5bar, 2.6bar, 2.7bar, 2.8bar, 2.9bar, 3.0bar, 3.1bar, 3.2bar, 3.3bar, The range formed by 3.4bar, 3.5bar or any two of the above values as endpoints.
  • the dispersion gas pressure is 2.5bar to 3.5bar. Further, the dispersion air pressure is 3.5bar. Further, the dispersion air pressure is 2.5bar.
  • the hopper gap is a range formed by 1.2mm, 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm or any two of the above values as endpoints.
  • the hopper gap is 1.3 mm to 1.7 mm. Further, the hopper gap is 1.5mm.
  • the dry injector is an Areo S dry injector.
  • the laser particle size analyzer is a Malvern Mastersizer 3000 laser particle size analyzer.
  • the dapagliflozin API is dapagliflozin propylene glycol monohydrate, which has the following structural characteristics:
  • the acceptance criteria USP429 particle size determination method: for substances larger than 10 ⁇ m, the RSD (relative standard deviation) of D50 is ⁇ 10%, and the RSD of D10 and D90 is ⁇ 15%; for substances smaller than 10 ⁇ m, The RSD of D50 is ⁇ 20%, and the RSD of D10 and D90 is ⁇ 30%.
  • This example is a method for measuring the particle size of dapagliflozin raw material. The steps are as follows:
  • the injector is the Areo S dry sampler. Set the parameters: the mode is universal mode, the hopper gap is 1.5mm, the sample measurement time is 10s, the injection speed is 30%, and the dispersion air pressure is 3.5bar.
  • API sample 300 mg of crushed dapagliflozin propylene glycol monohydrate API (hereinafter referred to as API sample) into the sample hopper. After the background measurement is completed, measure the sample particle size. Three groups of API samples were measured in parallel from the same batch.
  • This example is a method for measuring the particle size of dapagliflozin raw material.
  • the steps are the same as in Example 1, and the parameter settings are as follows:
  • Example 1 Referring to the measurement method of Example 1, weigh about 300 mg of raw drug sample, a total of 6 parts, set the hopper gap to 1.5 mm, the sampling speed to 30%, the dispersion air pressure to 3.5 bar, and the measurement time to 10 s to measure the sample particle size.
  • Comparative Example 1 Weigh about 100 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 30%, the dispersion pressure to 3.5 bar, the measurement time to 10 s, and measure the sample particle size.
  • Comparative Example 2 Weigh about 200 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 30%, the dispersion air pressure to 3.5 bar, the measurement time to 10 s, and measure the sample particle size.
  • Comparative Example 3 Weigh about 300 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.0 mm, the sampling speed to 30%, the dispersion air pressure to 3.5 bar, the measurement time to 10 s, and measure the sample particle size.
  • Comparative Example 4 Weigh about 300mg of raw material sample, a total of 3 parts, set the hopper gap to 2.0mm, and inject the sample The speed is 30%, the dispersion pressure is 3.5bar, the measurement time is 10s, and the sample particle size is measured.
  • Comparative Example 5 Weigh about 300 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 20%, the dispersion pressure to 3.5 bar, the measurement time to 10 s, and measure the sample particle size.
  • Comparative Example 6 Weigh about 300 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 40%, the dispersion pressure to 3.5 bar, the measurement time to 10 seconds, and measure the sample particle size.
  • Comparative Example 7 Weigh about 300 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 30%, the dispersion air pressure to 4.0 bar, the measurement time to 10 s, and measure the sample particle size.
  • Comparative Example 8 Weigh about 300 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 30%, the dispersion pressure to 3.5 bar, the measurement time to 5 seconds, and measure the sample particle size.
  • Comparative Example 9 Weigh about 300 mg of raw drug sample, a total of 3 parts, set the hopper gap to 1.5 mm, the sampling speed to 30%, the dispersion air pressure to 3.5 bar, the measurement time to 15 s, and measure the sample particle size.

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  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de mesure de la dimension des particules d'un agent pharmaceutique actif de dapagliflozine, comprenant les étapes suivantes consistant à : prendre l'agent pharmaceutique actif de dapagliflozine à mesurer, injecter celui-ci dans un analyseur de dimension des particules pour une mesure de dimension des particules, l'analyseur de dimension des particules étant un analyseur laser de dimension des particules, un espace de trémie étant situé dans la plage allant de 1,2 mm à 1,8 mm, une pression de dispersion étant située dans la plage allant de 2 bar à 3,5 bar, un injecteur utilisé pour l'injection d'échantillon étant un injecteur par procédé à sec, un volume d'injection étant situé dans la plage allant de 220 mg à 350 mg, et une vitesse d'injection étant située dans la plage allant de 25 % à 35 %. Le présent procédé de mesure de la dimension des particules de l'agent pharmaceutique actif de dapagliflozine est basé sur une combinaison d'un analyseur laser de dimension des particules et d'une injection d'échantillon par procédé à sec, et au moyen d'une optimisation complète de divers paramètres, tels que le volume d'injection, l'espace de trémie, la vitesse d'injection, la pression de dispersion, etc., un procédé de mesure ayant une bonne répétabilité et une précision intermédiaire élevée étant obtenu, ce qui répond aux exigences de contrôle de la pharmacopée pour la détermination de dimension des particules d'agents pharmaceutiques actifs. De plus, le procédé est simple et facile à mettre en œuvre.
PCT/CN2023/104365 2022-08-17 2023-06-30 Procédé de mesure de la dimension des particules d'agent pharmaceutique actif de dapagliflozine Ceased WO2024037221A1 (fr)

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CN202210988089.1A CN115343198A (zh) 2022-08-17 2022-08-17 达格列净原料药的粒径测定方法
CN202210988089.1 2022-08-17

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115343198A (zh) * 2022-08-17 2022-11-15 扬子江药业集团上海海尼药业有限公司 达格列净原料药的粒径测定方法
CN116297048A (zh) * 2023-02-10 2023-06-23 鲁南贝特制药有限公司 一种替比培南匹酯粒径检测方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018097570A2 (fr) * 2016-11-24 2018-05-31 한미약품 주식회사 Formulation pharmaceutique comprenant de la l-proline de dapagliflozine
WO2018124468A1 (fr) * 2016-12-30 2018-07-05 한미약품주식회사 Composition pharmaceutique contenant de la dapagliflozine l-proline pour prévenir ou traiter le diabète
CN109115661A (zh) * 2018-09-27 2019-01-01 湖北省宏源药业科技股份有限公司 一种用来测定阿奇霉素原料药粒径及粒度分布的方法
CN113654956A (zh) * 2021-07-27 2021-11-16 广州白云山医药集团股份有限公司白云山制药总厂 阿莫西林原料药的粒径和粒度分布的测定方法
CN114062208A (zh) * 2021-11-18 2022-02-18 上海新亚药业闵行有限公司 一种头孢氨苄粒度的分析方法
CN115343198A (zh) * 2022-08-17 2022-11-15 扬子江药业集团上海海尼药业有限公司 达格列净原料药的粒径测定方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018097570A2 (fr) * 2016-11-24 2018-05-31 한미약품 주식회사 Formulation pharmaceutique comprenant de la l-proline de dapagliflozine
WO2018124468A1 (fr) * 2016-12-30 2018-07-05 한미약품주식회사 Composition pharmaceutique contenant de la dapagliflozine l-proline pour prévenir ou traiter le diabète
CN109115661A (zh) * 2018-09-27 2019-01-01 湖北省宏源药业科技股份有限公司 一种用来测定阿奇霉素原料药粒径及粒度分布的方法
CN113654956A (zh) * 2021-07-27 2021-11-16 广州白云山医药集团股份有限公司白云山制药总厂 阿莫西林原料药的粒径和粒度分布的测定方法
CN114002118A (zh) * 2021-07-27 2022-02-01 广州白云山医药集团股份有限公司白云山制药总厂 一种阿莫西林原料药粒度测定方法
CN114062208A (zh) * 2021-11-18 2022-02-18 上海新亚药业闵行有限公司 一种头孢氨苄粒度的分析方法
CN115343198A (zh) * 2022-08-17 2022-11-15 扬子江药业集团上海海尼药业有限公司 达格列净原料药的粒径测定方法

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