WO2000077017A1 - Forme amorphe de clarithromycine - Google Patents

Forme amorphe de clarithromycine Download PDF

Info

Publication number
WO2000077017A1
WO2000077017A1 PCT/IB2000/000762 IB0000762W WO0077017A1 WO 2000077017 A1 WO2000077017 A1 WO 2000077017A1 IB 0000762 W IB0000762 W IB 0000762W WO 0077017 A1 WO0077017 A1 WO 0077017A1
Authority
WO
WIPO (PCT)
Prior art keywords
clarithromycin
amorphous
amorphous form
crystalline
solvent
Prior art date
Application number
PCT/IB2000/000762
Other languages
English (en)
Inventor
Naresh Kumar
Mohammad Salman
Kiran Kumar Gangakhedkar
Original Assignee
Ranbaxy Laboratories 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
Priority claimed from IN866DE1999 external-priority patent/IN190843B/en
Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Priority to AU49428/00A priority Critical patent/AU4942800A/en
Publication of WO2000077017A1 publication Critical patent/WO2000077017A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • This invention relates to novel amorphous form of 6-0-methylerythro-
  • mcyin A (Clarithromycin)
  • composition containing it containing it.
  • Clarithromycin is a useful therapy for
  • Clarithromycin Two distinctly different forms of Clarithromycin (Forms I and II) have been described in two U.S. patents, Nos. 5,838,986 and 5,844,105. Furthermore, these U.S. patents describe that these two forms have very different intrinsic dissolution rates; Form-I showed three-times faster intrinsic dissolution rate as compared with Form-ll.
  • the present invention describes an amorphous form of Clarithromycin which has an even better intrinsic dissolution and methods of preparing such a Clarithromycin in this, hitherto unknown, solid form which would be essentially free of any crystallinity.
  • clarithromycin in an amorphous form.
  • Clarithromycin in an amorphous form is prepared by an efficient process which is a further aspect of the present invention and which comprises dissolving crystalline clarithromycin (Form I or Form II) in a solvent followed by recovering amorphous form from its solution by spray drying or by grinding action between the two surfaces.
  • the amorphous clarithromycin thus obtained may be formulated with one or more pharmaceutical carriers or excipients.
  • Figure 1 is an infrared spectrum showing peaks characteristic of amorphous clarithromycin.
  • Figure 2 is an X-ray powder diffraction (XRD) pattern of amorphous clarithromycin.
  • Figure 3 is an infrared spectrum showing peaks characteristic of crystalline Form I of clarithromycin obtained per U.S. Patent No. 5,838,986.
  • Figure 4 is an infrared spectrum showing peaks characteristic of crystalline Form II of clarithromycin obtained per U.S. Patent No. 5,844,105.
  • Figure 5 is an XRD pattern showing peaks characteristic of crystalline form I of clarithromycin obtained per U.S. Patent No. 5,838,986.
  • Figure 6 is an XRD pattern showing peaks characteristic of crystalline form II of clarithromycin obtained per U.S. Patent No. 5,844,105.
  • Clarithromycin in new amorphous form is obtained by a process which comprises dissolving crystalline clarithromycin (Form-I or Form-ll) in a solvent followed by recovering amorphous form of clarithromycin from the solution thereof by spray drying or by grinding action between two surfaces.
  • solvent includes ketones, chlorinated solvents, ethers, esters, alcohols, or mixture(s) thereof.
  • the solvent may be selected from the group consisting of acetone, dichloromethane, chloroform, tetrahydrofuran, 1 ,4-dioxane, ethyl acetate, methanol, ethanol or mixtures thereof.
  • clarithromycin is recovered from the solution in an amorphous form using a spray drying technique.
  • the mini-spray Dryer (Model: Buchi 190, Switzerland) which operates on the principle of nozzle spraying in a parallel - flow, i.e. the sprayed product and the drying gas flow in the same direction.
  • the drying gas can be air or inert gases such as nitrogen, argon, or carbon dioxide. Nitrogen is preferred in this case.
  • the crystalline clarithromycin is milled by grinding action between two surfaces till the time we get amorphous clarithromycin essentially free of any crystallinity.
  • Such milling can be carried out by using a traditional technique of compounding using a pestle and mortar or by milling machines that essentially work on the same principle. Examples of such milling machines include various makes of ball mills, roller mills, gyratory mills, and the like.
  • Amorphous clarithromycin prepared according to the process of the present invention may be characterized by its infra-red spectrum ( Figure 1) and by its X-ray powder diffraction pattern ( Figure 2).
  • the infra-red spectrum ( Figure 1) obtained for the sample, prepared by the process of the present invention is different from the infra-red spectra of crystalline forms (I and II) ( Figure 3 and Figure 4) of Clarithromycin.
  • X-ray powder diffraction patterns of the newly prepared form also gave a plain halo ( Figure 2) and show no peaks which are characteristic of the crystalline forms I and II of Clarithromycin ( Figure 5 and Figure 6), thus demonstrating the amorphous nature of the product.
  • Clarithromycin (40 g) in an amorphous form was thus isolated.
  • Example 3 The process of Example 1 was repeated with crystalline clarithromycin (100 g) using dichloromethane (600 ml) instead of acetone to give amorphous clarithromycin (83 g) IR (KBr) and X-ray crystallography confirmed that the material was amorphous.
  • EXAMPLE 3 The process of Example 1 was repeated with crystalline clarithromycin (100 g) using dichloromethane (600 ml) instead of acetone to give amorphous clarithromycin (83 g) IR (KBr) and X-ray crystallography confirmed that the material was amorphous.

Abstract

La présente invention concerne une forme amorphe de 6-0-méthylérythromcyine A (Clarithromycine), un procédé permettant sa préparation et une composition la contenant.
PCT/IB2000/000762 1999-06-11 2000-06-07 Forme amorphe de clarithromycine WO2000077017A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49428/00A AU4942800A (en) 1999-06-11 2000-06-07 Novel amorphous form of clarithromycin

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN866/DEL/99 1999-06-11
IN866DE1999 IN190843B (fr) 1999-06-11 1999-06-11
US58756100A 2000-06-05 2000-06-05
US09/587,561 2000-06-05

Publications (1)

Publication Number Publication Date
WO2000077017A1 true WO2000077017A1 (fr) 2000-12-21

Family

ID=26324680

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2000/000762 WO2000077017A1 (fr) 1999-06-11 2000-06-07 Forme amorphe de clarithromycine

Country Status (2)

Country Link
AU (1) AU4942800A (fr)
WO (1) WO2000077017A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1254146A1 (fr) * 1999-12-16 2002-11-06 Teva Pharmaceutical Industries Ltd. Procedes de preparation de polymorphes de clarithromycine et nouveau polymorphe iv
US8337733B2 (en) 2007-08-17 2012-12-25 Abbott Gmbh & Co. Kg Preparation of compositions with essentially noncrystalline embedded macrolide antibiotics

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5844105A (en) * 1996-07-29 1998-12-01 Abbott Laboratories Preparation of crystal form II of clarithromycin
US5858986A (en) * 1996-07-29 1999-01-12 Abbott Laboratories Crystal form I of clarithromycin

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5844105A (en) * 1996-07-29 1998-12-01 Abbott Laboratories Preparation of crystal form II of clarithromycin
US5858986A (en) * 1996-07-29 1999-01-12 Abbott Laboratories Crystal form I of clarithromycin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
E.YONEMOCHI ET AL.: "Physiochemical Properties of Amorphous Clarithromycin Obtained by Grinding and Spray Drying.", EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 7, no. 4, March 1999 (1999-03-01), pages 331 - 338, XP000925447 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1254146A1 (fr) * 1999-12-16 2002-11-06 Teva Pharmaceutical Industries Ltd. Procedes de preparation de polymorphes de clarithromycine et nouveau polymorphe iv
EP1254146A4 (fr) * 1999-12-16 2003-04-16 Teva Pharma Procedes de preparation de polymorphes de clarithromycine et nouveau polymorphe iv
US8337733B2 (en) 2007-08-17 2012-12-25 Abbott Gmbh & Co. Kg Preparation of compositions with essentially noncrystalline embedded macrolide antibiotics

Also Published As

Publication number Publication date
AU4942800A (en) 2001-01-02

Similar Documents

Publication Publication Date Title
CA2663776C (fr) Rifaximin sous forme amorphe
US7704960B2 (en) Macrolide compounds endowed with antiinflammatory activity
US5635613A (en) Process for preparing crystal forms and solvates of dirithromycin
US6602999B1 (en) Amorphous form of cefpodoxime proxetil
EP1619198B1 (fr) Procédé pour la préparation du cefuroxim acetil en forme amorphe
HU218787B (hu) Új eritromicinszármazékok, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
JPS59104398A (ja) エピ化アザホモエリスロマイシンａ誘導体
WO2005108412A1 (fr) Macrolides a liaison ester utiles pour le traitement d'infection microbiennes
AU2019237276A1 (en) A novel form of ivermectin and a process for making it
JPH01186900A (ja) アミカシンの合成方法
WO2000077017A1 (fr) Forme amorphe de clarithromycine
JPS5853000B2 (ja) 新規抗菌剤
EP2262780A2 (fr) Tartrate de varénicline amorphe
CA2369255C (fr) Amelioration de la methode de preparation de dihydrate d'azithromycine non-hygroscopique
CA2748847A1 (fr) Macrolide anti-inflammatoire
EP1627883A1 (fr) Dérivés de 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A
HU220631B1 (hu) Antibiotikus hatású eritromicin A 9-0-oxim -származékok, ezeket tartalmazó gyógyszerkészítmények és a vegyületek alkalmazása gyógyszerkészítmények előállítására
EP1328535B1 (fr) Macrolides
HU182559B (en) Process for producing 4-two comma above-deoxy-4-two comma above-amino-erythromycin a derivatives of antibacterial activity
WO2007029265A2 (fr) Procede pour preparer de la clarithromycine et des produits intermediaires de la clarithromycine
JP2006507315A (ja) ９−デオキソ−９−ジヒドロ−９ａ−アザ−９ａ−ホモエリスロマイシンＡ及び５−Ｏ−デソサミニル−９−デオキソ−９−ジヒドロ−９ａ−アザ−９ａ−ホモエリスロノリドＡの置換した９ａ−Ｎ−｛Ｎ’−［４−（スルホニル）フェニルカルバモイル］｝誘導体
KR100367981B1 (ko) 클라리스로마이신 결정형 2의 제조 방법 및 이 방법에사용되는 결정성 클라리스로마이신 메실레이트 삼수화물
Raimondo et al. Unusual isoxazoline formation by intramolecular cyclization of (9E)-erythromycin A oxime
WO2004110399A2 (fr) Solvates de cefprozil
WO2005066196A1 (fr) Forme amorphe de finasteride et procede de preparation associe

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP