EP1399422A2 - Nouvelles formes cristallines d'acide 4- 4- 4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl-a,a- dimethylbenzene acetique et son chlorhydrate - Google Patents

Nouvelles formes cristallines d'acide 4- 4- 4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl-a,a- dimethylbenzene acetique et son chlorhydrate

Info

Publication number
EP1399422A2
EP1399422A2 EP01956057A EP01956057A EP1399422A2 EP 1399422 A2 EP1399422 A2 EP 1399422A2 EP 01956057 A EP01956057 A EP 01956057A EP 01956057 A EP01956057 A EP 01956057A EP 1399422 A2 EP1399422 A2 EP 1399422A2
Authority
EP
European Patent Office
Prior art keywords
fexofenadine
organic solvent
hours
hydrochloride
hydroxydiphenylmethyl
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.)
Withdrawn
Application number
EP01956057A
Other languages
German (de)
English (en)
Inventor
M. Satyanarayana Reddy
S. Thirumalai Rajan
U. V. Bhaskara Rao
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.)
Dr Reddys Laboratories Ltd
Original Assignee
Dr Reddys Laboratories 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 Dr Reddys Laboratories Ltd filed Critical Dr Reddys Laboratories Ltd
Priority to EP10010066A priority Critical patent/EP2261209A1/fr
Publication of EP1399422A2 publication Critical patent/EP1399422A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a novel crystalline form of fexofenadine hydrochloride and to a process for the preparation thereof. More specifically, the present invention relates to a novel anhydrous crystalline Form X of fexofenadine hydrochloride. The present invention also relates to a novel crystalline form of fexofenadine, particularly Form A of fexofenadine and to a process for the preparation thereof.
  • Chemically fexofenadine hydrochloride is 4-[4- [4- (hydroxydiphenylmethyl) -1- piperidinyl] — l-hydroxybutyl]- , ⁇ - dimethylbenzene acetic acid hydrochloride. It is also known as terfenadine carboxylic acid metabolite. It is represented by Formula 1.
  • Fexofenadine hydrochloride is useful as an antihistamine, and does not cause the adverse effects associated with the administration of terfenadine including abnormal heart rhythms in some patients with liver disease or patients who also take the antifungal drug ketoconazole or the antibiotic erythromycin.
  • U.S. Patent No. 4,254,129 entitled Piperidine Derivatives issued on March 3, 1981.
  • the ' 129 patent relates to substituted piperidine derivatives and methods of making and using them.
  • the disclosed compounds, including fexofenadine and its pharmaceutically acceptable salts and individual optical isomers, are purported to be useful as antihistamines, antiallergy agents and bronchodilators.
  • the '129 patent discloses a process for the preparation of fexofenadine having a melting point of 195-197°C.
  • the recrystallization process exemplified therein in Example 3, column 13, involves use of a mixture of solvents for preparation of fexofenadine.
  • WO 95/31437 discloses processes for preparing hydrated and anhydrous forms of piperidine derivatives, polymorphs and pseudomorphs thereof, which are useful as antihistamines, antiallergic agents and bronchodilators.
  • WO 95/31437 discloses the preparation of anhydrous forms of fexofenadine hydrochloride by subjecting the hydrated fexofenadine hydrochloride to an azeotropic distillation or to water minimizing recrystallization.
  • hydrated Fexofenadine unlike the process described in WO95/31437, hydrated Fexofenadine
  • Hydrochloride is not converted to anhydrous Fexofenadine Hydrochloride, but instead
  • Fexofenadine is converted to Form A of Fexofenadine and then to anhydrous Form X of Fexofenadine Hydrochloride.
  • the novel anhydrous crystalline form of Fexofenadine Hydrochloride is obtained according to the present invention directly from the novel precursor i.e. Fexofenadine without generating a hydrated form.
  • the starting material used Fexofenadine (Base) is different than described in WO 95/31437.
  • WO 00/71124A1 discloses amorphous fexofenadine hydrochloride process, its preparation and a composition containing it.
  • Fexofenadine obtained in the prior art processes is a mixture of regioisomers of fexofenadine containing 33% of para isomer and 67% of meta isomer. These components are referred to as inseparable and it is also stated that it is not possible to obtain either of the regioisomers in substantially pure form.
  • Fexofenadine prepared according to the process of this invention has a purity of > 99.5%. i the novel crystalline Fexofenadine of this invention, the meta isomer of Fexofenadine is at a level of below 0.1%.
  • fexofenadine Purity of fexofenadine is critical when it is used for the conversion to its hydrochloride salt since it is very difficult to remove any undesired impurities, including regioisomers, from the desired compound in last late processing stage. Removing the impurities increases the cost of production. Hence it is generally preferred that the HPLC purity of fexofenadine is greater than 99.5 %.
  • the fexofenadine hydrochloride is obtained in almost quantitative yield from the precursor i.e. fexofenadine.
  • Almost quantitative yield means that the pure fexofenadine is converted to fexofenadine hydrochloride quantitatively ( > 92 % yield of theory ), with almost no yield loss, as the fexofenadine base itself is >99.5 % pure as compared to fexofenadine prepared by the prior art processes.
  • an object of the present invention is to provide a novel crystalline form of fexofenadine and a process for its preparation.
  • Another object of the present invention is to provide a novel anhydrous crystalline form of fexofenadine hydrochloride (Formula 1) and a process for its preparation, which can be obtained directly from fexofenadine without generating a hydrated form of fexofenadine hydrochloride.
  • a further object of the present invention is to provide pure novel polymorphs of fexofenadine and its hydrochloride by a simple process which is cost effective, commercially viable and environmentally friendly.
  • Fig.l is a characteristic X-ray powder diffraction pattern of Form A of fexofenadine.
  • Vertical axis Intensity (CPS); Horizontal axis: Two Theta (degrees).
  • the sigmficant d values (A 0 ) obtained are 23.11, 11.50, 8.29, 7.03, 6.67, 6.16, 6.02, 5.75, 5.43, 5.33, 5.07, 4.69, 4.63, 4.44, 4.20, 4.15, 4.07, 3.55, and 3.44.
  • Fig.2 is a characteristic infrared absorption spectrum in potassium bromide of aforementioned Form A of fexofenadine. [Vertical axis, Tramission (%); Horizontal axis: Wave number (cm '1 )]. The characteristic peaks for Form A are indicated at 3421,
  • Fig.3 is a characteristic of differential scanning calorimetry thermogram of aforesaid Form A of Fexofenadine. Vertical axis: mW; Horizontal axis: Temperature
  • the DSC thermogram exhibits a melt endotherm at about 230.38°C.
  • Fig. 4 is a characteristic X-ray powder diffraction pattern of Form X of fexofenadine hydrochloride.
  • Vertical axis Intensity (CPS); Horizontal axis: Two Theta
  • Fig.5 is a characteristic infrared absorption spectrum in potassium bromide of aforementioned Form X of Fexofenadine hydrochloride. [Vertical axis, Tramission (%); Horizontal axis: Wave number (cm "1 )]. The characteristic peaks for Form X are indicated at 3370, 2965, 2652, 1717, 1472, 1448, 1250, 1158, 1100,1068, 995, 962, 840,
  • Fig.6 is a characteristic of differential scanning calorimetry thermogram of aforesaid Form X of Fexofenadine hydrochloride.
  • the DSC thermogram exhibits a melt endotherm at about 186.56°C.
  • the present invention provides a novel crystalline form of Fexofenadine, which is designated as Form A for convenience.
  • the process for the preparation of novel crystalline Form A comprises recrystallization of crude fexofenadine in an alcohol followed by azeotropically refluxing Fexofenadine in a non polar organic solvent, organic solvent or a mixture thereof and the subsequent isolation of the desired Form A.
  • Form A is prepared by a process, which comprises : a. recrystallizing crude Fexofenadine in a (C 1 -C 3 )alkanol followed by; b.
  • Crude fexofenadine can be recrystallized in methanol, ethanol or isopropanol, preferably methanol.
  • the ratio of crude Fexofenadine to the (C1-C 3 ) alkanol is 1:10-20.
  • the ratio of fexofenadine to nonpolar organic solvent and/or organic solvent in step b) is 1:10-15.
  • the non polar organic solvents referred to herein are selected from xylene or toluene or a (C 6 -C 9 ) alkyl such as n-hexane, hexane, heptane, octane, nonane or cyclohexane.
  • Toluene is the preferred non polar organic solvent.
  • the organic solvents are (Ci to C ) alkyl acetates and are selected from methyl, ethyl, propyl, and butyl acetate, preferably ethyl acetate.
  • the present invention provides a process for preparing a novel crystalline form of Fexofenadine Hydrochloride, designated as Form X.
  • the process for the preparation of novel crystalline Form X of fexofenadine hydrochloride comprises reaction of fexofenadine Form A in non polar solvent, with a suitable solvent containing hydrogen chloride and isolating the desired Form X of fexofenadine hydrochloride which can be obtained directly from fexofenadine without generating a hydrated form of fexofenadine hydrochloride.
  • the Form X polymorph is prepared by a process, which comprises: a. recrystallizing crude Fexofenadine in (CrC 3 )alkanol followed by; b. azeotropically refluxing Fexofenadine in a non polar orgamc solvent, an organic solvent or mixtures thereof for 15 minutes to 6 hours, preferably 1-3 hours; c. stirring the reaction mixture at ambient temperature for 30 min to 2 hours; d. optionally isolating the Fexofenadine Form A by conventional methods ; e. if isolated, suspending Fexofenadine Form A, in a non polar organic solvent; f.
  • adjusting the pH of the reaction mass to 1 to 3, preferably 2 with a suitable solvent containing hydrogen chloride; g. stirring the reaction mass for 30 minutes to 18 hours, preferably 1-10 hours and more preferably 3-6 hours at ambient temperature; h. filtering the solid obtained followed by drying at 60-100°C; i. suspending the solid obtained in step (h) in an alkyl acetate and heating the reaction mixture to reflux for 0.5 -6 hours preferably 1-3 hours; j. stirring the reaction mixture at ambient temperature for 20 minutes to 2 hours; and k.
  • the preparation of Form X can be accomplished without isolation of Form A.
  • the preparation of Form X can proceed directly from step (c) to step (f) eliminating steps (d) and (e).
  • the preparation of novel Form X polymorph may be accomplished by drying the solid obtained in step (h) at 110-160°C under reduced pressure for 30 minutes to 10 hours, preferably 2-5 hours.
  • the ratio of solid to alkyl acetate in step (i) is 1:10-15.
  • Yet another aspect of the present invention is to provide a process for preparing a novel crystalline form of Fexofenadine Hydrochloride, designated as Form X, by seeding technique.
  • This process comprises: a. recrystallizing crude Fexofenadine in a (C 1 -C 3 )alkanol followed by; b. azeotropically refluxing Fexofenadine in a non polar organic solvent for 3-4 hours; c. optionally isolating the Fexofenadine Form A obtained in step b) by conventional methods accompanied by drying at below 100°C ; d.
  • step c) suspending the Fexofenadine Form A obtained in step c) or adding to the mixture of step b) a mixture of a nonpolar organic solvents selected from toluene or xylene or a (C ( ,-C 9 )alkyl; or an organic solvent selected from (C 1 -C 4 ) alkyl acetate preferably ethyl acetate; and isopropanol, the ratio of solvent to isopropanol being 7-9:3-
  • step d adjusting the pH of the solution of step d) to 1 to 3 preferably 2 with a suitable solvent containing hydrogen chloride; f. filtering the solution obtained in step e) to remove particulate matter; g. seeding the solution of step f) with crystals of novel crystalline Form X and stirring the reaction mass at ambient temperature to separate the solid; h.
  • the crude fexofenadine maybe recrystallized in a C1-C 3 alkanol such as methanol, ethanol or isopropanol, preferably, methanol.
  • a C1-C 3 alkanol such as methanol, ethanol or isopropanol, preferably, methanol.
  • the non polar organic solvents referred to herein are selected from xylene or toluene or a (C 6 -C 9 ) alkyl such as n-hexane, hexane, heptane, octane, nonane or cyclohexane. Mixtures of solvents may be used thereof. Toluene is the preferred solvent.
  • the organic solvents are (C ⁇ -C ) alkyl acetates and are selected from methyl, ethyl, propyl and butyl acetate preferably ethyl acetate.
  • the suitable solvent containing hydrogen chloride referred to herein is selected from methanol, ethanol, isopropanol or t-butanol, preferably isopropanol.
  • the ratio of crude fexofenadine to the Ci-C 3 alkanol is 1:10-20.
  • the ratio of fexofenadine to the solvents in step b. is 1:10-15.
  • the hydrocarbon solvent is selected from hexane or cyclohexane, preferably cyclohexane.
  • the present invention provides a improved method for the preparation of Fexofenadine Form A in its pure form by a crystallization process which requires onlya single solvent. This solvent may be recovered and reused, thereby rendering the process cost effective and environmentally friendly.
  • novel polymorphic forms of fexofenadine of this invention may if desired be converted into one of its pharmaceutically acceptable salts.
  • Fexofenadine and its hydrochloride obtained by the present invention are pure and well suited for formulation.
  • Most pharmaceuticals formulation processes are faciliated by use of the active materials that are free flowing high melting solids.
  • the novel anhydrous crystalline Form A and X of Fexofenadine Hydrochloride of the present invention are a high melting solid, very suited for fo ⁇ nulation. Examples
  • the samples were scanned between 3-45 degrees 2 ⁇ .
  • the infrared absorption spectra were recorded in solid state as KBr dispersion on
  • the samples were heated to 250°C at a heating rate of 5°C / min with a 30ml/minute nitrogen purge.

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un nouveau polymorphe de la fexofenadine et du chlorhydrate de fexofenadine de formule (1), ainsi que son procédé de préparation. L'invention concerne par ailleurs de nouveaux polymorphes purs de fexofenadine et de son chlorhydrate par un procédé simple, peu coûteux, commercialement viable et convivial.
EP01956057A 2001-06-18 2001-07-31 Nouvelles formes cristallines d'acide 4- 4- 4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl-a,a- dimethylbenzene acetique et son chlorhydrate Withdrawn EP1399422A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10010066A EP2261209A1 (fr) 2001-06-18 2001-07-31 Nouvelles formes crystallines d'acide acetique de 4-[4-[4- Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzene et leur acide chlorhydrique

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN484MA2001 2001-06-18
INMA20010484 2001-06-18
PCT/US2001/023994 WO2002102777A2 (fr) 2001-06-18 2001-07-31 Nouvelles formes cristallines d'acide 4-[4-[4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl]-$g(a)-$g(a)- dimethylbenzene acetique et son chlorhydrate

Publications (1)

Publication Number Publication Date
EP1399422A2 true EP1399422A2 (fr) 2004-03-24

Family

ID=34566868

Family Applications (2)

Application Number Title Priority Date Filing Date
EP01956057A Withdrawn EP1399422A2 (fr) 2001-06-18 2001-07-31 Nouvelles formes cristallines d'acide 4- 4- 4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl-a,a- dimethylbenzene acetique et son chlorhydrate
EP10010066A Withdrawn EP2261209A1 (fr) 2001-06-18 2001-07-31 Nouvelles formes crystallines d'acide acetique de 4-[4-[4- Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzene et leur acide chlorhydrique

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP10010066A Withdrawn EP2261209A1 (fr) 2001-06-18 2001-07-31 Nouvelles formes crystallines d'acide acetique de 4-[4-[4- Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzene et leur acide chlorhydrique

Country Status (20)

Country Link
EP (2) EP1399422A2 (fr)
JP (2) JP2005507374A (fr)
KR (1) KR20040015734A (fr)
CN (1) CN100390145C (fr)
AU (1) AU2001278094B2 (fr)
BG (1) BG108435A (fr)
BR (1) BR0117054A (fr)
CA (2) CA2450858C (fr)
CO (1) CO5540340A2 (fr)
CZ (1) CZ20033358A3 (fr)
EE (1) EE200400010A (fr)
HU (1) HUP0401546A2 (fr)
IL (2) IL159266A0 (fr)
MX (1) MXPA03011728A (fr)
NZ (1) NZ530118A (fr)
PL (1) PL367632A1 (fr)
RU (1) RU2269516C2 (fr)
SK (1) SK15372003A3 (fr)
WO (1) WO2002102777A2 (fr)
ZA (1) ZA200309557B (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ20033019A3 (cs) * 2001-04-09 2004-07-14 Teva Pharmaceutical Industries Ltd. Polymorfní formy chloridu fexofenadinu
ES2239554T1 (es) 2002-06-10 2005-10-01 Teva Pharmaceutical Industries Ltd. Forma xvi polimorfica de hidrocloruro de fexofenadina.
GB0319935D0 (en) * 2003-08-26 2003-09-24 Cipla Ltd Polymorphs
US20050256163A1 (en) * 2004-04-26 2005-11-17 Ilan Kor Crystalline forms of fexofenadine hydrochloride and processes for their preparation
ITMI20041143A1 (it) * 2004-06-08 2004-09-08 Dipharma Spa Polimorfi di fexofenadina e procedimento per la loro preparazione
ITMI20041568A1 (it) * 2004-07-30 2004-10-30 Dipharma Spa "polimorfi di fexofenadina base"
JP2008514641A (ja) * 2004-09-28 2008-05-08 テバ ファーマシューティカル インダストリーズ リミティド 結晶形フェキソフェナジン、およびその調製方法
WO2007007347A1 (fr) * 2005-07-07 2007-01-18 Wockhardt Limited Procédé industriel de préparation du chlorhydrate de fexofénadine avec un minimum de produits secondaires
RU2283649C1 (ru) * 2005-10-27 2006-09-20 Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") Фармацевтическая композиция для лечения аллергических заболеваний
EP2105134A1 (fr) 2008-03-24 2009-09-30 Ranbaxy Laboratories Limited Hydrochlorure de fexofenadine amorphe stable
CN104072402B (zh) * 2014-07-16 2016-08-17 昆山龙灯瑞迪制药有限公司 一种新结晶形式的盐酸非索非那定化合物及其制备方法

Citations (1)

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Publication number Priority date Publication date Assignee Title
WO1995031437A1 (fr) * 1994-05-18 1995-11-23 Hoechst Marrion Roussel, Inc. Procedes de preparation de formes anhydres et hydratees de derives de piperidine antihistaminiques, polymorphes et pseudomorphes de ces dernieres

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US4254129A (en) * 1979-04-10 1981-03-03 Richardson-Merrell Inc. Piperidine derivatives
DE9320925U1 (de) * 1992-08-03 1995-08-31 Georgetown University, Washington, D.C. Terfenadin-Metabolite und deren optisch reine Isomere für die Behandlung von allergischen Störungen
US6153754A (en) * 1995-12-21 2000-11-28 Albany Molecular Research, Inc. Process for production of piperidine derivatives
IN191492B (fr) * 1999-05-25 2003-12-06 Ranbaxy Lab Ltd
GB0018691D0 (en) * 2000-07-28 2000-09-20 Rolabo Sl Process

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995031437A1 (fr) * 1994-05-18 1995-11-23 Hoechst Marrion Roussel, Inc. Procedes de preparation de formes anhydres et hydratees de derives de piperidine antihistaminiques, polymorphes et pseudomorphes de ces dernieres

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ALEXANDRA GOHO: "Tricky Business - The crystal form of a drug can be the secret to its succes", SCIENCE NEWS ONLINE, vol. 166, no. 8, 2004 *
MINO R. CAIRA: "Crystalline Polymorphism of Organic Compounds", TOPICS IN CURRENT CHEMISTRY, vol. 198, 1998, pages 163 - 208, XP001156954 *
See also references of WO02102777A2 *

Also Published As

Publication number Publication date
RU2269516C2 (ru) 2006-02-10
EE200400010A (et) 2004-02-16
BR0117054A (pt) 2004-07-27
BG108435A (en) 2004-12-30
IL159266A (en) 2010-11-30
MXPA03011728A (es) 2004-07-08
CN1518540A (zh) 2004-08-04
PL367632A1 (en) 2005-03-07
AU2001278094B2 (en) 2006-01-12
CZ20033358A3 (en) 2004-04-14
CA2450858C (fr) 2009-04-07
NZ530118A (en) 2007-05-31
WO2002102777A3 (fr) 2003-02-27
RU2004101045A (ru) 2005-06-27
CA2646802A1 (fr) 2002-12-27
CA2450858A1 (fr) 2002-12-27
CO5540340A2 (es) 2005-07-29
WO2002102777A2 (fr) 2002-12-27
JP2008094848A (ja) 2008-04-24
JP2005507374A (ja) 2005-03-17
IL159266A0 (en) 2004-06-01
WO2002102777A8 (fr) 2003-10-30
HUP0401546A2 (hu) 2004-12-28
ZA200309557B (en) 2004-09-14
CN100390145C (zh) 2008-05-28
KR20040015734A (ko) 2004-02-19
SK15372003A3 (sk) 2004-08-03
EP2261209A1 (fr) 2010-12-15

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