[go: up one dir, main page]

WO2012062916A1 - Succinate de solifénacine cristallin - Google Patents

Succinate de solifénacine cristallin Download PDF

Info

Publication number
WO2012062916A1
WO2012062916A1 PCT/EP2011/069969 EP2011069969W WO2012062916A1 WO 2012062916 A1 WO2012062916 A1 WO 2012062916A1 EP 2011069969 W EP2011069969 W EP 2011069969W WO 2012062916 A1 WO2012062916 A1 WO 2012062916A1
Authority
WO
WIPO (PCT)
Prior art keywords
solifenacin succinate
crystalline
length ratio
axial length
crystalline solifenacin
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/EP2011/069969
Other languages
German (de)
English (en)
Inventor
Max Born
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.)
Hexal AG
Original Assignee
Hexal AG
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 Hexal AG filed Critical Hexal AG
Priority to CA2817336A priority Critical patent/CA2817336A1/fr
Priority to EP11782419.3A priority patent/EP2638039A1/fr
Publication of WO2012062916A1 publication Critical patent/WO2012062916A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system

Definitions

  • the present invention relates to crystalline solifenacin succinate, its use, a process for the preparation of solifenacin succinate, a solifenacin succinate preparable by the process and its use.
  • Solifenacin is a drug of the pharmacotherapeutic group of urological spasmolytics for the treatment of symptoms of overactive bladder and is described in international patent application WO 96/020194. Solifenacin is used as a solifenacin succinate in pharmaceutical applications, also known as butanedioic acid: (IS) - (3R) -1-azabicyclo [2.2.2] oct-3-yl 3,4-dihydro-1-phenyl-2 (1H) - isoquinolinecarboxylate (1: 1). Solifenacin is approved for the symptomatic treatment of urge incontinence or pollakiuria and imperative urgency, as may occur in patients with overactive bladder syndrome. Solifenacin is a competitive, specific, cholinergic receptor antagonist.
  • solifenacin The mechanism of action of solifenacin is that the bladder is innervated by parasympathetic cholinergic nerves. Acetylcholine causes a smooth muscle contraction of the detrusor muscle via muscarinic receptors, mainly via the M3 subtype. Solifenacin competitively and specifically inhibits the M3 subtype muscarinic receptor because it has little or no affinity for various other receptors and ion channels.
  • Solifenacin succinate is light in water and moderately soluble in organic solvents.
  • the prior art discloses a crystalline modification of solifenacin succinate and amorphous solifenacin succinate.
  • the amorphous substance is chemically unstable and easily forms degradation products.
  • solifenacin succinate crystallizes teterrorism from organic solvents and solvent mixtures.
  • EP 1 832 288 A1 used solvent mixtures such as ethyl acetate / EtOH.
  • solvent mixtures such as ethyl acetate / EtOH.
  • solifenacin succinate crystallizes in the form of long nails.
  • Such acicular solifenacin succinate tends to clump, resulting in a number of technological problems in the preparation of pharmaceutical compositions and formulations.
  • EP 2 088 148 A2 describes processes for the preparation of solifenacin and its salts, such as solifenacin succinate.
  • the resulting solifenacin succinate is crystallized from a mixture of ethanol and ethyl acetate. In this case, however, the product is obtained in long needles, which are disadvantageous due to the poor flow and processing properties.
  • US 2008/0114028 A1 describes processes for preparing polymorphic forms of solifenacin succinate wherein the solifenacin succinate is crystallized from solvents and solvent mixtures such as mixtures of methanol and acetone. In this case, however, the product is obtained in long needles, which are disadvantageous due to the poor flow and processing properties.
  • solifenacin succinate which has better flowability than the acicular crystalline solifenacin succinate known in the art.
  • the objects are achieved in a first aspect by a crystalline solifenacin succinate, wherein the solifenacin succinate has a mean axis length ratio of 5: 1 or less, preferably a mean axial length ratio of 5: 1 to 1: 1, particularly preferably a middle Axis length ratio of 1: 1 and having at least one of the following properties:
  • the solifenacin succinate a mean axial length ratio of 5: 1 or smaller, preferably an average axial length ratio of 5: 1 to 1: 1, more preferably a mean axial length ratio of 1: 1;
  • the solifenacin succinate a) has a mean axial length ratio of 5: 1 or smaller, preferably a mean axial length ratio of 5: 1 to 1: 1, more preferably a mean axial length ratio of 1: 1;
  • the solifenacin succinate has the following properties: a) a mean axial length ratio of 5: 1 or smaller, preferably a mean axial length ratio of 5: 1 to 1: 1, more preferably a mean axial length ratio of 1: 1;
  • solifenacin succinate has the following properties:
  • (B) a mean particle size of about 2 to 40 ⁇ , preferably 5 to 30 ⁇ .
  • the objects are achieved by a crystalline solifenacin succinate, wherein the solifenacin succinate has a mean axis length ratio of 5: 1 or less, preferably a mean axial length ratio of 5: 1 to 1: 1, particularly preferably a middle one Axial length ratio of 1: 1.
  • a crystalline solifenacin succinate wherein the solifenacin succinate has a mean axis length ratio of 5: 1 or less, preferably a mean axial length ratio of 5: 1 to 1: 1, particularly preferably a middle one Axial length ratio of 1: 1.
  • the objects are achieved in a third aspect by a crystalline solifenacin succinate, the solifenacin succinate having a particle size d 0.9 ⁇ 200 ⁇ m, preferably d 0.9 ⁇ 150 ⁇ m, and particularly preferably d 0.9 ⁇ 100 ⁇ is having.
  • This also represents a first embodiment of the third aspect.
  • the objects in a fourth aspect are achieved by a crystalline solifenacin succinate, wherein the solifenacin succinate has an average particle size of about 2 to 40 ⁇ m, preferably 5 to 30 ⁇ m. This also represents a first embodiment of the fourth aspect.
  • the objects in a fifth aspect are achieved by a crystalline solifenacin succinate, wherein the solifenacin succinate peaks in the powder X-ray diffractogram at 3.7; 11.1; 18.6, 21.8 ° 2 ⁇ ⁇ 0.2 ° 2 ⁇ . This also represents a first embodiment of the fifth aspect.
  • the particle size is determined or determined by means of laser diffraction.
  • first, second, third, fourth and fifth aspects which is also an embodiment of any embodiment of the first, second, third, fourth and fifth aspects, it is provided that d 0.9 ⁇ 150 ⁇ and preferably d 0 , 9 ⁇ 100 ⁇ is.
  • the mean grain size is about 5 to 30 ⁇ .
  • the mean grain size is or will be determined by laser diffraction.
  • the powder X-ray diffractogram is determined by means of X-ray diffractometry in Bragg-Brentano Geometry over an angular range of 3 - 45 ° and a copper cathode is created or will.
  • the powder X-ray diffractogram is substantially as shown in FIG shown powder X-ray diffractogram is.
  • the crystalline solifenacin succinate may contain more than 10% by weight. % of solifenacin succinate with a powder X-ray diffractogram, wherein the powder X-ray diffraction shows peaks at 3.7; 11.1; 18.6; 21.8 ° 2 ⁇ ⁇ 0.2 ° 2 ⁇ .
  • the crystalline solifenacin succinate is a micronized solifenacin succinate
  • the crystalline solifenacin succinate of the invention may be provided and / or suitable is for the manufacture of a medicament, wherein in a further embodiment it is provided that the medicament is a solid dosage form. In a more preferred embodiment, it is provided that the solid dosage form is a tablet, preferably a divisible tablet.
  • the medicament may be used in its various embodiments or is suitable for use in the treatment and / or prevention of a disease or condition wherein the disease and / or condition is selected from the group consisting of overactive bladder symptoms, urge incontinence , Pollakisuria and imperative urgency.
  • the solifenacin succinate of the present invention is or will be useful in the manufacture of a medicament, which medicament is or may be a solid dosage form in its various forms as described herein or known to those skilled in the art.
  • the dosage form contains a content of ⁇ 5 mg of solifenacin succinate, preferably of ⁇ 2.5 mg of solifenacin succinate and particularly preferably of ⁇ 1 mg of solifenacin succinate.
  • the solifenacin succinate is used or is suitable for Use in a method of treating a subject, preferably a human, the method comprising administering to the vegetarian a pharmaceutically effective amount of the crystalline solifenacin succinate.
  • the objects in a sixth aspect are solved by the use of the crystalline solifenacin succinate according to the present invention and in particular according to any embodiment of the first, second, third, fourth and fifth aspects for the preparation of a medicament.
  • This is also a first embodiment of the first aspect.
  • the medicament is suitable or used for the treatment and / or prevention of a disease or a condition, wherein the disease and / or the condition is selected from the group comprising symptoms of overactive bladder, Urge incontinence, pollakisuria and imperative urgency.
  • the objects are achieved in a seventh aspect by a process for the preparation of crystalline solifenacin succinate, wherein it is provided that crystalline solifenacin succinate is used as starting material, wherein the solifenacin succinate used as starting material is a crystalline solifenacin succinate .
  • the starting material is subjected to a crushing step, wherein in the crushing step, the particle size and / or the mean grain size and / or the axial length ratio of the starting material is reduced.
  • This also represents a first embodiment of the seventh aspect.
  • the comminuting step comprises a measure selected from the group consisting of sublimation, grinding, micronizing and wet micronizing.
  • the solifenacin succinate to be prepared is a crystalline solifenacin succinate according to any embodiment of the first, second, third, fourth, fifth and sixth aspect of the present invention.
  • the crystalline solifenacin used as the starting material has peaks in the powder X-ray diffractogram at 3.7; 11.1, 18.6; 21.8 ° 2 ⁇ ⁇ 0.2 ° 2 ⁇ .
  • the disintegration step is performed to the extent or until the average axial length ratio of the solifenacin succinate 5 Is 1 or smaller, preferably the average axial length ratio of the solifenacin succinate is from 5: 1 to 1: 1, and more preferably the average axial length ratio is 1: 1.
  • the objects in an eighth aspect are achieved by a crystalline solifenacin succinate obtainable by a process according to the seventh aspect Aspect of the present invention and its various embodiments. This also represents a first embodiment of the eighth aspect.
  • solifenacin succinate is intended or suitable for use as described herein in connection with the first, second, third, Fourth, fifth and sixth aspects of the present invention and their respective embodiments is described.
  • the form of solifenacin succinate described herein, and in particular of crystalline solifenacin succinate, is also referred to herein as solifenacin succinate according to the invention or solifenacin succinate according to the invention.
  • solifenacin succinate which has at least one of the following four properties: a) an average aspect ratio of 5: 1 or less, preferably a center aspect ratio of 5: 1 to 1: 1, more preferably a mean axial length ratio of 1: 1;
  • solifenacin succinate is also referred to herein as solifenacin succinate according to the invention or solifenacin succinate according to the invention.
  • this new form of solifenacin succinate has a very good flow behavior with the indicated axial ratio and / or small particle size.
  • this property of the solifenacin according to the invention seems to be based on it may be that the needle shape of the solifenacin is less pronounced than in the prior art solifinacin. This property is preferably expressed in a relatively low axial ratio or lower axial ratio compared with the prior art solifenacin.
  • the inventors believe that the advantageous properties of the crystalline solifenacin according to the present invention, and in particular the crystalline solifenacin succinate according to the present invention, are justified by the fact that the axial ratio of the crystalline solifenacin according to the present invention Invention compared to the axial ratio of solifenacin succinate according to the prior art is reduced.
  • Such a reduction in the axial ratio of crystalline solifenacin succinate can be obtained, for example, by sublimation, milling, micronization and wet micronization of a suitable starting material.
  • the starting material used is a crystalline solifenacin succinate whose peaks in the powder X-ray diffractogram correspond to those of the crystalline solifenacin succinate according to the present invention.
  • the peaks in the powder X-ray diffractogram are 3.7; 11.1; 18.6; 21.8 ° 2 ⁇ ⁇ 0.2 ° 2 ⁇ .
  • the combination of the axial length ratio according to the invention with the particle size according to the invention and / or the grain size according to the invention has a particularly advantageous flow behavior and leads to particularly good processing properties of solifenacin succinate.
  • the solifenacin succinate according to the invention has an axial length ratio, as described herein, and furthermore a particle size distribution of d 0.1> 5 ⁇ m, d 0.5 of ⁇ 150 ⁇ m and d 0.9 ⁇ 200 ⁇ m and / or a mean particle size of> 2 ⁇ , preferably of> 5 ⁇ .
  • solifenacin succinate overcomes the disadvantages of acyclic crystalline solifenacin succinate described in the prior art.
  • the solifenacin succinate according to the present invention is particularly characterized in its handling properties in that it has better flow properties over the acicular crystalline form of solifenacin succinate. Such better flow properties are manifested inter alia in improved aggregative properties and a lower tendency to clump together, as well as a greater fluidity.
  • the solifenacin succinate according to the invention exhibits a higher bulk density.
  • the axial length ratio referred to herein as the mean axial length ratio, is determined by measuring the solifenacin succinate crystals in their axial and longitudinal directions by light microscopic photographs.
  • solifenacin succinate crystals which are randomly selected from a sample, measured by light microscopic images and their extent in the axial direction and determined in the longitudinal direction.
  • the longitudinal extent corresponds to the maximum distance between two opposite points of a solifenacin succinate crystal, the dimension in the axial direction of the minimum distance between two opposite points transverse to the longitudinal direction, measured at the center of the longitudinal axis.
  • the mean axis length ratio is determined from the average of the obtained measurements of at least 10 randomly selected crystals.
  • the solifenacin succinate according to the invention can be used advantageously because of its properties, in particular in the production of tablets and more precisely in the direct compression tablet production, which is one of the most important, economical and elegant methods of tablet production.
  • the flowability of the powder mixtures is a prerequisite for direct compression, also referred to as direct tabletting, since controlled uniform flow of the powders in the tabletting machines is essential for the controlled processing of the tablets in the tablet presses. If, as with the use of solifenacin succinate particles according to the prior art, the mass to be tabletted is stagnated, tablets which are too light can be produced. Furthermore, the components can segregate. Non-uniform mixtures lead to fluctuations in the active substance content.
  • solifenacin succinate according to the invention provides a form of solifenacin succinate which is suitable for use in the preparation of pharmaceutical compositions and which can be used therefor, the pharmaceutical compositions being in particular those containing a small amount of solifenacin succinate containing an amount of solifenacin succinate, the amount being allowed to vary only within narrow tolerances between the individual compositions and in particular the individual tablets, or the uniform distribution of the active ingredient, ie solifenacin succinate, within the individual composition and especially within a single tablet.
  • compositions in which the solifenacin succinate according to the invention can be used in a particularly advantageous manner are divisible tablets and scored tablets known to those skilled in the art and utilizing these in light of the technical teaching herein solifenacin succinate according to the present invention.
  • dosage forms are described, inter alia, in Bauer / Frömming / Guide “Textbook of Pharmaceutical Technology", chapter “tablets”, or the European Pharmacopoeia 6.1 in the chapter “tablets”.
  • the determination of the particle size is known to those skilled in the art and exemplified in the example part herein and in European Pharmacopoeia 6.1, chap. 09/02/31 "Particle size determination by laser light diffraction" described.
  • the particle size determination is typically carried out by laser diffraction in silicone oil.
  • a Malvern Mastersizer 2000 is used for particle size determination.
  • the suspension of solifenacin succinate and silicone oil is treated for one minute in an ultrasonic bath.
  • d (0.5) or d 0.5 is the value at which 50% of the particles are below a subsequently indicated size.
  • the d (0.9) or d 0.9 is the value at which 90% of the particles are below a subsequently specified size.
  • FIG. 2 is a light micrograph of solifenacin succinate crystals as obtained according to Example 1 (10-fold magnification in paraffin oil);
  • FIG. 3 is a photomicrograph of solifenacin succinate crystals as obtained according to Example 2 (40X magnification in paraffin oil); FIG.
  • Fig. 4 is a graph showing the grain size distribution of solifenacin succinate according to Example 2 as measured by laser diffraction;
  • Fig. 5 is a photomicrograph of solifenacin succinate crystals as obtained according to Example 3.
  • Fig. 6 is a graph showing the grain size distribution of solifenacin succinate according to Example 3 as measured by laser diffraction;
  • Fig. 7 is a photomicrograph of solifenacin succinate crystals as obtained according to Example 4.
  • Fig. 8 is a graph showing the grain size distribution of solifenacin succinate according to Example 4 as measured by laser diffraction;
  • Figure 9 is a photomicrograph of solifenacin succinate crystals as obtained according to the teachings of EP 1 714 956 A1;
  • Figure H is a photomicrograph of solifenacin succinate crystals as obtained according to Comparative Example 3 after recrystallization in a mixture of ethyl acetate and acetone.
  • the crystalline solifenacin succinate thus obtained was examined by light microscopy; the light-microscopic image is reproduced as FIG.
  • the determined axial length ratio is about 2.5: 1.
  • a powder X-ray diffractogram was prepared, which is reproduced as FIG.
  • Example 2 Preparation of solifenacin succinate according to the invention Needle-shaped crystalline solifenacin succinate with Bragg peaks at 3.7; 11.1; 18.6; 21.8 0 2 ⁇ ⁇ 0.2 ° 2 ⁇ was placed in a hand mortar and mortared for about 1 minute using a pestle. The mortared substance had a good flow behavior and did not clump. The crystalline solifenacin succinate thus obtained was examined by light microscopy; the light-microscopic image is reproduced as FIG. The determined axial length ratio is approximately 1: 1.
  • Crystalline solifenacin succinate with Bragg peaks at 3.7; 11.1; 18.6; 21.8 ° 2 ⁇ ⁇ 0.2 ° 2 ⁇ was placed in a Retsch vibrating mill type MM 301 and ground for about 2 minutes at 10 Hz in a metal container intended for this device with the aid of a ball.
  • the crystalline solifenacin succinate thus obtained was examined by light microscopy; the light-microscopic image is reproduced as FIG. 5.
  • the determined axial length ratio is approx. 1.5: 1.
  • Crystalline solifenacin succinate with Bragg peaks at 3.7; 11.1; 18.6; 21.8 ° 2 was placed in a Retsch vibrating mill type MM 301 and ground for about 10 minutes at 15 Hz in a metal container intended for this device with the aid of a ball.
  • the crystalline solifenacin succinate thus obtained was examined by light microscopy; the light microscopic image is reproduced as FIG.
  • the determined axial length ratio is approximately 1: 1.
  • solifenacin succinate was dissolved in 2.3 ml of ethyl acetate and 0.45 ml of ethanol and cooled to 0 ° C.
  • the crystals were of poor flow property and strongly agglomerated.
  • the crystalline solifenacin succinate thus obtained was examined by light microscopy; the light-microscopic image is reproduced as FIG. 9.
  • the determined axial length ratio is approximately 6: 1.
  • the crystalline solifenacin succinate thus obtained was examined by light microscopy; the light microscopic image is reproduced as FIG. 11.
  • the determined axial length ratio is approximately 10: 1.
  • a tablet having an active ingredient content of 5 mg of solifenacin succinate according to the invention was prepared as follows and had the following composition.
  • the powder X-ray diffractograms were carried out on a Panalytical X'Pert Pro series (manufacturer Panalytical).
  • the device settings were as follows:
  • the sample was measured by backloading or on zero-background-holder. It was measured with a Soller gap 0.02 rad using a nickel filter. Particle Size Determination
  • For particle size determination typically 50 mg of substance were moistened in a test tube with 5 drops of silicone oil and suspended on a vortexer. 6 ml of silicone oil were added and resuspended on a vortexer. The suspension was sonicated for 1 minute in an ultrasonic bath. Subsequently, a homogeneous suspension was prepared on the vortexer. By drawing and emptying a pipette in the suspension, the homogenization was quite fast. Subsequently, so much suspension was added with the aid of the pipette into the sample application unit of a Mastersizer until a shading of 10 - 25% was achieved. It was measured without any waiting time.
  • the microscope images were taken on a DMLB transmitted light microscope from Leica. For this purpose, a spatula tip of substance was placed on a microscope slide and drizzled with 1 -2 drops of paraffin oil. A coverslip was used to create a uniform suspension on the slide. Determination of the axial length ratio
  • the mean axial length ratio was determined from the light microscopy images by determining the longitudinal extent and transverse dimension as described herein, the reported value being the average of measured values of at least 10 randomly selected crystals.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne du succinate de solifénacine cristallin, le succinate de solifénacine présentant un rapport des longueurs moyennes des axes de 5:1 ou moins, de préférence un rapport des longueurs moyennes des axes de 5:1 à 1:1, de manière particulièrement préférée un rapport des longueurs moyennes des axes de 1:1 et au moins une des propriétés suivantes : a) une grosseur des particules d 0,9 < 200 μm ; b) une grosseur moyenne des grains d'environ 2 à 40 μm ; et c) des pics dans le diffractogramme des rayons X réalisé sur une poudre à 3,7 ; 11,1 ; 18,6 ; 21,8° 2Θ ± 0,2° 2Θ.
PCT/EP2011/069969 2010-11-11 2011-11-11 Succinate de solifénacine cristallin Ceased WO2012062916A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CA2817336A CA2817336A1 (fr) 2010-11-11 2011-11-11 Succinate de solifenacine cristallin
EP11782419.3A EP2638039A1 (fr) 2010-11-11 2011-11-11 Succinate de solifénacine cristallin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP10014527 2010-11-11
EP10014527.5 2010-11-11

Publications (1)

Publication Number Publication Date
WO2012062916A1 true WO2012062916A1 (fr) 2012-05-18

Family

ID=43663592

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/069969 Ceased WO2012062916A1 (fr) 2010-11-11 2011-11-11 Succinate de solifénacine cristallin

Country Status (3)

Country Link
EP (1) EP2638039A1 (fr)
CA (1) CA2817336A1 (fr)
WO (1) WO2012062916A1 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996020194A1 (fr) 1994-12-28 1996-07-04 Yamanouchi Pharmaceutical Co., Ltd. Nouveaux derives de quinuclidine et composition pharmaceutique les contenant
EP1714965A1 (fr) 2004-02-09 2006-10-25 Astellas Pharma Inc. Composition contenant du succinate de solifenacine
EP1726304A1 (fr) 2004-03-16 2006-11-29 Astellas Pharma Inc. Composition contenant de la solifenacine
EP1832288A1 (fr) 2004-12-27 2007-09-12 Astellas Pharma Inc. Préparation pharmaceutique granulaire stable de solifénacine ou de son sel
US20080114028A1 (en) 2006-07-24 2008-05-15 Tamas Koltai Process for preparing polymorphic forms of solifenacin succinate
US20080242697A1 (en) 2007-03-30 2008-10-02 Medichem, S.A. Process for the synthesis of solifenacin
US20090099365A1 (en) 2007-07-13 2009-04-16 Nurit Perlman Processes for solifenacin preparation
EP2088148A2 (fr) 2008-02-08 2009-08-12 Dipharma Francis S.r.l. Procédé de préparation de solifénacine
WO2009139002A2 (fr) 2008-05-12 2009-11-19 Msn Laboratories Limited Procédé perfectionné de fabrication de solifénacine et de ses sels pharmaceutiquement acceptables
WO2010012459A2 (fr) * 2008-07-29 2010-02-04 Krka, D.D., Novo Mesto Procédé de préparation de sels de solifénacine et inclusion de ces derniers dans des formes pharmaceutiques

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996020194A1 (fr) 1994-12-28 1996-07-04 Yamanouchi Pharmaceutical Co., Ltd. Nouveaux derives de quinuclidine et composition pharmaceutique les contenant
EP1714965A1 (fr) 2004-02-09 2006-10-25 Astellas Pharma Inc. Composition contenant du succinate de solifenacine
EP1726304A1 (fr) 2004-03-16 2006-11-29 Astellas Pharma Inc. Composition contenant de la solifenacine
EP1832288A1 (fr) 2004-12-27 2007-09-12 Astellas Pharma Inc. Préparation pharmaceutique granulaire stable de solifénacine ou de son sel
US20080114028A1 (en) 2006-07-24 2008-05-15 Tamas Koltai Process for preparing polymorphic forms of solifenacin succinate
US20080242697A1 (en) 2007-03-30 2008-10-02 Medichem, S.A. Process for the synthesis of solifenacin
US20090099365A1 (en) 2007-07-13 2009-04-16 Nurit Perlman Processes for solifenacin preparation
EP2088148A2 (fr) 2008-02-08 2009-08-12 Dipharma Francis S.r.l. Procédé de préparation de solifénacine
WO2009139002A2 (fr) 2008-05-12 2009-11-19 Msn Laboratories Limited Procédé perfectionné de fabrication de solifénacine et de ses sels pharmaceutiquement acceptables
WO2010012459A2 (fr) * 2008-07-29 2010-02-04 Krka, D.D., Novo Mesto Procédé de préparation de sels de solifénacine et inclusion de ces derniers dans des formes pharmaceutiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NAGAKAWA S ET AL.: "The abstract of Lectures at the Memorial Symposium for the Foundation of the", JAPAN PROCESS CHEMISTRY ASSOCIATION, 4 July 2002 (2002-07-04), pages 85 - 86

Also Published As

Publication number Publication date
EP2638039A1 (fr) 2013-09-18
CA2817336A1 (fr) 2012-05-18

Similar Documents

Publication Publication Date Title
DE102008037025B4 (de) Kristalline Wirkstoff-Mikropartikel, Verfahren zu deren Herstellung und Verwendung in Arzneimitteln
EP2477660B1 (fr) Composition pharmaceutique renfermant les agents actifs metformine et sitagliptine ou vildagliptine
EP2364141B2 (fr) Moxifloxacine compactée
DE3503681A1 (de) Pharmazeutische zusammensetzungen
DE69821119T2 (de) Neuartige formulierung zur inhalation mit einer bulkdichte zwischen 0.28 und 0.38 g/ml, mit formoterol
DE69233678T2 (de) Agglomerate mit hohem ibuprofen-gehalt und deren herstellungsverfahren
WO2005117896A1 (fr) Formulations contenant du fasudil, une matrice et une enveloppe
EP2531178B1 (fr) Carbonate d&#39;hydroxyde de magnésium compressible par voie direct
DE69326470T2 (de) Wasserdispergierbare tabletten
EP1940359B1 (fr) Procede pour produire des formulations d&#39;ibuprofene pouvant etre directement mises sous forme de comprimes
DE69434600T2 (de) Pharmazeutische Zusammensetzungen, die Paracetamol und L-Cystein oder eine Vorstufe davon enthalten
EP2416761A1 (fr) Desfésotérodine sous forme de sel d&#39;acide tartrique
WO2012062916A1 (fr) Succinate de solifénacine cristallin
WO2007073782A1 (fr) Composition pharmaceutique contenant de l&#39;hydrochlorure de donepezil, comprime a base de cette composition et procede de production associe
WO2017045742A1 (fr) Formulation à libération retardée contrôlée du principe actif
EP3349732A1 (fr) Comprimés à libération des principes actifs indépendante des substances de libération
DE10393805T5 (de) Pharmazeutische Formulierungen, die ß-2-Adrenorezeptor-Agonisten und Xantine enthalten
DE10350528A1 (de) Arzneimittelformulierung, enthaltend einen LTB4-Antagonisten, sowie Verfahren zu deren Herstellung und deren Verwendung
EP3487484B1 (fr) Composition d&#39;atorvastatine
DE10316087A1 (de) Polymorphstabilisierung von Fluvastatin-Natrium in Pharmazeutischen Formulierungen
EP2544685B1 (fr) Composition pharmaceutique solide contenant de l&#39;hydrochlorure de donepezil de la forme 1 polymorphe cristalline
DE2621906A1 (de) Neue therapeutische mischung und verfahren zu deren herstellung
EP1663150A2 (fr) Nouvelle poudre pour inhaler contenant l&#39;antagoniste de cgrp 1-[n2-[3,5-dibromo-n-[[4-(3,4-dihydro-2(1h)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazine
EP2214648A2 (fr) Statines stabilisées
EP1962845A2 (fr) Composition pharmaceutique contenant de l&#39;hydrochlorure de donepezil, comprime a base de cette composition et procede de production associe

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11782419

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2817336

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2011782419

Country of ref document: EP