WO2013114232A1 - Procédé de préparation de forme cristalline l d'ilaprazole - Google Patents

Procédé de préparation de forme cristalline l d'ilaprazole Download PDF

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Publication number
WO2013114232A1
WO2013114232A1 PCT/IB2013/050327 IB2013050327W WO2013114232A1 WO 2013114232 A1 WO2013114232 A1 WO 2013114232A1 IB 2013050327 W IB2013050327 W IB 2013050327W WO 2013114232 A1 WO2013114232 A1 WO 2013114232A1
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WIPO (PCT)
Prior art keywords
ilaprazole
crystalline form
preparation
peaks
mixture
Prior art date
Application number
PCT/IB2013/050327
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English (en)
Inventor
Nikhil Shashikant BHATT
Madan Kumar Sharma
Priya Deepak RAKSHE
Chinal Indravadan SHAH
Suresh Nagjibhai KANTRODIYA
Sachin Jasvant PATEL
Pradhuman Amrutsinh PARMAR
Pravin Shamjibhai PATEL
Original Assignee
Lupin Limited
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 Lupin Limited filed Critical Lupin Limited
Publication of WO2013114232A1 publication Critical patent/WO2013114232A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

  • the present invention relates to the process for preparation of crystalline form L of ilaprazole.
  • the present invention further relates to the novel crystalline form L of ilaprazole.
  • the present invention further relates to the novel crystalline form L of ilaprazole formed by said process.
  • Ilaprazole is a proton pump inhibitor (PPI) used in the treatment of dyspepsia, peptic ulcer disease, gastroesophageal reflux disease and duodenal ulcer.
  • PPI proton pump inhibitor
  • Ilaprazole is chemically known as 2-[[(4-methoxy-3-methyl-2-pyridinyl)methyl]sulfinyl]- 6-(lH-pyrrol-l-yl)-lH-benzimidazole havin following structure
  • the example 2 of Indian Patent No. 183088 describes crystallization of ilaprazole from mixture of ethyl acetate and ether.
  • Indian patent application No. 3607/DELNP/2009 discloses various crystalline forms: A, B, E, F, I of ilaprazole and process for their preparation.
  • the crystalline form B of ilaprazole is obtained by crystallization from acetone/triethylamine in a refrigerator for 11 days.
  • the form B is characterized by peaks at 12.6 and 18.1 degree 2 ⁇ in X-ray powder differactogram.
  • 3634/DELNP/2009 discloses various solvates of ilaprazole, these are crystalline form C (1,4-dioxane hemisolvate), D (tetrahydrofuran hemisolvate), G (methanol solvate), K (hydrate) of ilaprzole and process for their preparation.
  • the physical or chemical properties of a drug can vary depending on the crystalline form of the drug, and such physical and chemical properties can greatly influence a suitable dosage form of the drug, the optimization of a process for preparing the drug, and the in vivo absorption of the drug.
  • the discovery of the most appropriate crystalline form of a drug in a procedure for developing the drug enables the development time and cost to be reduced.
  • the present invention relates to the process for preparation of crystalline form L of ilaprazole comprising steps of:
  • Figure 1 X-ray powder differactogram of form L.
  • Ilaprazole used for crystallization may be crude, pure or exist in any polymorphic form or mixtures thereof.
  • the aliphatic ketone is selected from acetone, 2-butanone, 2-pentanone, 3-pentanone, 4- methyl pentanone, 2-methyl-3-pentanone and the like.
  • the aliphatic ketone is preferably acetone.
  • the quantity of aliphalic ketone may vary from 10 to 100 volumes per weight of the ilaprazole, preferably 40 to 50 volumes.
  • the tertiary organic amine is selected from trimethylamine, triethylamine, tripropylamine, triisopropylamine, dimethyl ethylamine, diethyl methylamine and the like.
  • the tertiary organic amine is preferably triethylamine.
  • the quantity of tertiary organic amine may vary in the range 0.001 to 0.1 w/w, preferably 0.01 to 0.05 w/w.
  • the heating may be performed at a temperature from 40 °C to the boiling point of the aliphatic ketone used.
  • Mixture may be cooled to -10 °C to 30 °C, preferably to 0 °C to 30 °C, most preferably to 20 °C to 25 °C.
  • Mixture is stirred for about one hour. The separation of the crystals occurs slowly. In case crystals are not separated, mixture is optionally seeded with form L.
  • the solid may be isolated by the known techniques such as filtration, concentration, evaporation etc.
  • form L a novel crystalline form of ilaprazole, referred as form L formed by the said process.
  • the said crystalline form L of ilaprazole is characterized by a powder X-ray diffraction pattern having peaks at 6.60, 8.24 and 16.05, ⁇ 0.2 degree 2 ⁇ .
  • the form L is further characterized by the additional peaks at 9.69, 13.15, 17.19 and 19.73 ⁇ 0.2 degree 2 ⁇ in XRPD spectrum.
  • the peaks found in XRPD of form L are given in the following table.
  • the XRPD of form L is as shown in figure 1.
  • the crystalline form L of ilaprazole is characterized by an infra-red spectrum having peaks at 1434 and 1417 ⁇ 5 cm "1 .
  • the form L is further characterized by the additional peaks at 1577, 1477, 1292, 1269, 1257, 1080, 1037, 806, 732 ⁇ 5 cm "1 in IR spectrum.
  • the IR spectrum of crystalline form L is as shown in figure 2.
  • the crystalline form L of ilaprazole characterized by differential scanning calorimetry (DSC) thermogram having an endotherm at 156 °C.
  • the DSC of crystalline form L is shown in figure 3.
  • the form L was found to be stable at 25 ⁇ 2 °C (60 ⁇ 5 RH).
  • the ilaprazole obtained by the present invention has sulfone impurity less than 0.1 %, individual impurity less than 0.15 %, total impurity less than 0.4 %; therefore suitable for pharmaceutical compositions.
  • the form L of ilaprazole of the present invention can be used in the preparation of pharmaceutical composition for inhibiting gastric acid secretion.
  • Such pharmaceutical composition can be prepared by the methods known in the literature.
  • the powder X-ray diffraction spectrum is measured using PANalytical X'Pert PRO diffractogram (copper anti cathode) and expressed in terms of inter planar distance d, bragg' s 2 theta, intensity and relative intensity (expressed as a percentage of the most intense peak).
  • the FTIR spectra were obtained using a Shimadzu 8400S instrument.
  • the differential scanning calorimetry (DSC) was done using Perkin Elmer DSC 4000 instrument.
  • the mixture was filtered through hyflow, washed with acetone (70 mL X 2).
  • Triethylamine (0.7 mL) was added to the combined filtrate and distilled under reduced pressure till 15 volumes acetone remains in the mixture.
  • the concentrated solution was stirred at 20-25 °C for 45-60 min. Seeds of form L were added to the concentrated solution and stirred at 0-5 °C for 5-6 hours. Solid was filtered, washed with acetone and dried. Yield: 31.0 g.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé de préparation de forme cristalline L d'ilaprazole comprenant les étapes suivantes : 1) chauffage du mélange d'ilaprazole dans une cétone aliphatique contenant une amine organique tertiaire, ii) refroidissement du mélange, iii) éventuellement, ensemencement avec une forme L et iv) isolement du solide. La présente invention concerne en outre la nouvelle forme cristalline L d'ilaprazole caractérisée par un profil de diffraction des rayons X par les poudres présentant des pics à 6,60, 8,24 et 16,05 ± 0,2 degré 28 et un spectre d'infra-rouges présentant des pics à 1417 et 1434 ± 5 cm-1.
PCT/IB2013/050327 2012-02-02 2013-01-14 Procédé de préparation de forme cristalline l d'ilaprazole WO2013114232A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN115/KOL/2012 2012-02-02
IN115KO2012 2012-02-02

Publications (1)

Publication Number Publication Date
WO2013114232A1 true WO2013114232A1 (fr) 2013-08-08

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Application Number Title Priority Date Filing Date
PCT/IB2013/050327 WO2013114232A1 (fr) 2012-02-02 2013-01-14 Procédé de préparation de forme cristalline l d'ilaprazole

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WO (1) WO2013114232A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008083333A1 (fr) * 2006-12-29 2008-07-10 Il Yang Pharmaceutical Company, Ltd. Formes à l'état solide de l'ilaprazole racémique
WO2008083319A1 (fr) * 2006-12-29 2008-07-10 Il Yang Pharmaceutical Company, Ltd. Formes à l'état solide de l'ilaprazole de pureté énantiomérique
CZ2009417A3 (cs) * 2009-06-30 2011-01-12 Zentiva, K.S. Nový zpusob výroby 2-[[(4-methoxy-3-methyl-2-pyridinyl)methyl]sulfinyl]-6-(1H-pyrrol-1-yl) 1H-benzimidazolu (ilaprazolu)
WO2011071314A2 (fr) 2009-12-08 2011-06-16 Il-Yang Pharm. Co., Ltd. Procédés de préparation de formes cristallines a et b d'ilaprazole et procédé de conversion des formes cristallines
CN102140092A (zh) * 2010-02-03 2011-08-03 丽珠医药集团股份有限公司 艾普拉唑盐的水合物及其制备方法和用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008083333A1 (fr) * 2006-12-29 2008-07-10 Il Yang Pharmaceutical Company, Ltd. Formes à l'état solide de l'ilaprazole racémique
WO2008083319A1 (fr) * 2006-12-29 2008-07-10 Il Yang Pharmaceutical Company, Ltd. Formes à l'état solide de l'ilaprazole de pureté énantiomérique
WO2008083341A1 (fr) * 2006-12-29 2008-07-10 Il Yang Pharmaceutical Company, Ltd. Formes cristallines d'ilaprazole solvaté
CZ2009417A3 (cs) * 2009-06-30 2011-01-12 Zentiva, K.S. Nový zpusob výroby 2-[[(4-methoxy-3-methyl-2-pyridinyl)methyl]sulfinyl]-6-(1H-pyrrol-1-yl) 1H-benzimidazolu (ilaprazolu)
WO2011071314A2 (fr) 2009-12-08 2011-06-16 Il-Yang Pharm. Co., Ltd. Procédés de préparation de formes cristallines a et b d'ilaprazole et procédé de conversion des formes cristallines
CN102140092A (zh) * 2010-02-03 2011-08-03 丽珠医药集团股份有限公司 艾普拉唑盐的水合物及其制备方法和用途

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