WO2006106135A1 - Crystal form of asenapine maleate - Google Patents
Crystal form of asenapine maleate Download PDFInfo
- Publication number
- WO2006106135A1 WO2006106135A1 PCT/EP2006/061408 EP2006061408W WO2006106135A1 WO 2006106135 A1 WO2006106135 A1 WO 2006106135A1 EP 2006061408 W EP2006061408 W EP 2006061408W WO 2006106135 A1 WO2006106135 A1 WO 2006106135A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- orthorhombic
- oxepino
- dibenz
- pyrrole
- tetrahydro
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
Definitions
- the invention relates to a new crystal form of asenapine, to methods for the preparation thereof and to pharmaceutical compositions comprising said crystal form.
- Asenapine is a compound for use in the treatment of central nervous system disorders, in particular schizophrenia.
- the chemical name of asenapine is trans-5- chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole and the preparation thereof is disclosed in USP No. 4,145,434.
- Asenapine is being developed as its maleate salt 2.
- This salt is prepared by adding one molar equivalent of an ethanolic solution of maleic acid to an ethanolic solution of asenapine I-, according to example 1.
- the thus obtained asenapine maleate 2 can be recrystallized from ethanol.
- the particle size of the drug substance influences biopharmaceutical properties of the drug product.
- the particle size of the drug substance affects drug product manufacturing and dissolution and hence its bioavailability. Since asenapine dissolves in the saliva the particle size is important. When drug substance particles are small, it takes only short periods of time to achieve high concentrations. From this perspective small particles are preferred. In addition, smaller particle size tends to improve the homogeneity of powder blends, which may result in improved uniformity of the contents of the drug product.
- the particle size, in terms of d95 is preferably about 100 ⁇ m or less, more preferably about 50 ⁇ m or less, and most preferably about 30 ⁇ m or less. As used throughout the disclosure, the term d95 means that 95% of the particles (based on volume) are smaller than or equal to the indicated size.
- the present invention provides an orthorhombic form of asenapine maleate, which through the use of a special crystallization technique, can be prepared in a highly pure form. Furthermore, the non-comminuted orthorhombic form has a comparatively smaller particle size (based on d95) than the non-comminuted monoclinic form of asenapine maleate. Moreover, it has been found that micronization of the orthorhombic form of asenapione maleate reproducibly results in microcr ⁇ stalline asenapine maleate of the orthorhombic form.
- one aspect of the invention provides an orthorhombic crystalline form of asenapine maleate, which contains 10% or less of another crystalline form, 5% or less of another crystalline form, or no detectable amount of another crystalline form, respectively.
- microcrystalline means that the form comprises particles having a size distribution characterized by a d95 of 30 ⁇ m or less.
- Yet another aspect of the invention provides a process for the preparation of the orthorhombic crystalline form of asenapine maleate.
- the process comprises crystallization of asenapine maleate by cooling from an ethanol/water mixture containing dissolved asenapine maleate.
- the mixture preferably is 9:1 v/v ethanol/water.
- a solution of asenapine maleate in the ethanol/water mixture can be seeded with such crystals.
- the crystallized material may further be disaggregated or screened to remove clusters of micro crystals.
- the crystalline asenapine maleate prepared according to the invention is a particular polymorphic form, which has a melting point in the range of 138-142 0 C.
- the crystal of the orthorhombic form of the present invention can be characterized, and thus distinguished from the monoclinic form, by several analytical techniques known in the art such as Infrared Spectroscopy, Raman Spectroscopy, Solid State Nuclear Magnetic Resonance Spectroscopy, Differential Scanning Calorimetry, X-ray powder diffraction patterns (XPRD) and many others. Such techniques may be applied individually or in combination.
- Figure 1 depicts XRPD patterns for the monocline form (upper pattern) and the orthorhombic form (lower pattern) of asenapine maleate. Each of the patterns is characterized by intensity peaks at certain specific values of the diffraction angle 2 theta ( ⁇ ).
- the most characteristic peaks are at 10.5 ° and 15.7 °.
- a 2-theta value as indicated typically means that specific value ⁇ 0.2.
- the orthorhombic form can also be characterized by its crystallographic data. Crystallographic data of the orthorhombic and monoclinic form obtained by single- crystal X-ray diffraction have been compared to each other. It was established that the crystal structure belonging to the monoclinic form consists of the space group P2i/n and 4 molecules in the unit cell, whereas the crystal structure belonging to the orthorhombic form consists of the space group Pca2i and 8 molecules in the unit cell.
- the data are shown in Tables 1a and 1 b.
- An axis length in Table 1a typically means that specific value ⁇ 0.2 A.
- a cell angle in Table 1a typically means that value ⁇ 0.2°
- An atomic position (x, y, z) in Table 1 b typically means those values ⁇ 0.002.
- Table 1A Crystallographic data concerning the unit cells of asenapine maleate monoclinic form and orthorhombic form
- the crystallographic data from Tables 1A and 1 B can be used to calculate X-ray powder diffraction patterns (XRPD patterns) of the monoclinic form and of the orthorhombic form of asenapine maleate. These calculated XRPD patterns of the monoclinic form and orthorhombic form of asenapine maleate can be used to compare with experimental patterns. Furthermore, the data from Table 1a can be used for a Pawley fit to compare experimental XRPD patterns to the crystallographic data of the monoclinic and orthorhombic form of asenapine maleate. Even more, the data from Table 1 b can be used for a Rietveld Refinement to compare experimental XRPD patterns to the crystallographic data of the monoclinic and orthorhombic form of asenapine maleate.
- XRPD patterns X-ray powder diffraction patterns
- the crystal of the orthorhombic form of the present invention can also be characterized, and thus distinguished from the monoclinic form, by their Raman spectra.
- Figure 2 depicts Raman spectra for monocline form (upper spectrum) and orthorhombic form (lower spectrum) of asenapine maleate.
- Table 1B Crystallographic data concerning the fractional atomic positions of asenapine maleate monoclinic form and orthorhombic form Each of the spectra is characterized by intensity peaks at certain specific values of wave number (cm 1 ).
- the monoclinic form has characteristic peaks at 3070 cm “1 , 3020 cm “1 , 2900 cm “1 , 2871 cm “1 , 2829 cm “1 , 1253 cm “1 , 1238 cm “1 , 849 cm “1 , 743 cm “1 and 711 cm “1 , with the more characteristic peaks being at 3070 cm “1 , 3020 cm “1 , 2871 cm “1 , 849 cm “1 and 711 cm “1 .
- the orthorhombic form is characterized by peaks at 3072 cm “1 , 3051 cm “1 , 3029 cm “1 , 3011 cm “1 , 2909 cm “1 , 2888 cm “1 , 1245 cm “1 , 824 cm “1 , 747 cm “1 , 717 cm “1 and 194 cm “1 , with the more characteristic peaks being at 3051 cm “1 , 3029 cm “1 , 3011 cm “1 , 2888 cm “1 , 824 cm “1 and 717 cm “1 . The most characteristic peaks are at 2888 cm “1 and 824 cm “1 .
- a wave number value as indicated above typically means that specific value ⁇ 2 cm "1 .
- the newly found advantageous property provides as a further aspect of the invention the use of asenapine maleate in the orthorhombic form for the preparation of fine crystal suspensions.
- a further aspect of the invention provides pharmaceutical preparations comprising the orthorhombic crystalline form of asenapine maleate in association with one or more pharmaceutically acceptable additives or excipients.
- amorphous asenapine maleate may be present.
- Such pharmaceutical preparations generally take the form of a dosage unit such as a tablet, a capsule or a suppository, but other solid or dry pharmaceutical preparations are included.
- a preferred pharmaceutical preparation is in the form of a tablet.
- a tablet may contain certain excipients in addition to the active principle asenapine maleate in the crystalline orthorhombic form such as diluents, binders, glidants and lubricants, which serve to impart satisfactory processing and compression characteristics to the tablet, as well as disintegrants and flavoring agents, which gives additional desirable physical characteristics to the finished tablet.
- a dosage unit of asenapine maleate, suitable for the treatment of mental disorders such as psychosis, bipolar disorders and schizophrenia may contain from about 0.005 to 500 mg of the active ingredient.
- a preferred dosage unit may contain 1-50 mg of asenapine maleate in the crystalline orthorhombic form.
- Figure 1 shows XRPD patterns of the monoclinic form (upper) and the orthorhombic form (lower) of trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1 H-dibenz[2,3:6,7]- oxepino[4,5-c]pyrrole (Z)-2-butenedioate measured in reflection.
- Figure 2 shows Raman spectra of the monoclinic form (upper) and the orthorhombic form (lower) of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H-dibenz[2,3:6,7]- oxepino[4,5-c]pyrrole (Z)-2-butenedioate.
- X-ray powder diffraction (XRPD) spectra were obtained on a XPert pro Panalytical Reflection diffractometer in a Bragg-Brantano setup, Cu-Ka radiation, settings 45 kV and 40 mA together with a X'celerator detector.
- the slits used anti-scatter slit 1°, divergence slit 1/2°, soller slits 0.02 rad.
- Measuring conditions scan range 5 - 40° 2- theta, step size 0.0167° 2-theta. The samples were measured on a rotating sample disk of Si with a speed of 15 rpm.
- the XRPD spectra of crystalline pure monoclinic form and pure orthorhombic form are depicted in Figure 1.
- the FT-Raman spectra were recorded using a Bruker RFS 100/S FT-Raman spectrometer equipped with a 1064 nm Adlas DPY 421 Nd:YAG laser with a maximum power of 1550 mW and a liquid nitrogen cooled Ge detector. For each sample, 128 scans were collected using a focussed beam (laserspot 100 ⁇ m), a laserpower of 150 mW and a resolution of 2 cm "1 .
- a dispersion liquid has been made consisting of (0.7 mg/ml) lecithin (used as a surfactant) in iso-octane saturated with asenapine maleate. The solution is stirred overnight. Subsequently the solution is filtered over a 0.22 ⁇ m filter. The samples were prepared by weighing approximately 30 mg asenapine maleate in a centrifugal tube and adding 2 ml of the dispersion liquid. Ultrasonic treatment of the samples was performed for 2 minutes in an ultrasonic bath (Transsonic 310). Subsequently, the particle size distribution of the sample was analyzed using laser diffraction (Malvern Mastersizer S, UK). The particle size distribution has been calculated using the Fraunhofer algorithm.
- DSC Differential Scanning Calorimetry
- the DSC equipment contained a measuring cell based on heat flux principle with a ceramic sensor and a furnace supply which can be used in the temperature range 0 to 300 °C.
- the heating rate was at least in the range of 1-20 °C/min.
- Purge gas was nitrogen (N 2 ) with a controlled flow of 50 mL/min.
- Asenapine maleate drug substance (2-5 mg) was accurately weighed in an aluminum sample pan.
- the applied heating rate was 5 °C/min and the temperature program was linear from 0-250 0 C.
- the reaction mixture was cooled to 20 0 C and stirred for 2 hours.
- the reaction mixture was then cooled to -10 °C ( ⁇ 2 0 C), stirred for 2 hours and the crystals were filtered.
- the crystals were washed with 5 L of ethanol (-10 0 C) and collected.
- the wet crystals are directly used in the recrystallization which is described in examples 2-8.
- Asenapine maleate (10 kg) prepared according to the procedure described in example 1 was dissolved in 24 L of ethanol at boiling temperature. After cooling at 20 °C the solution was stirred for 1 hour and cooled to -10 °C ( ⁇ 2 0 C). Stirring was continued for
- XRPD complies to reference of monoclinic polymorph
- Polymorphic purity -90% monoclinic form and 10% orthorhombic form
- Example 3 Crystallization of orthorhombic polymorph.
- Asenapine maleate (260 g) as prepared according to example 1 was dissolved in a mixture of ethanol (480 ml) and water (50 ml) by heating to 57 0 C. Then the solution was slowly allowed to cool and crystallization started. After stirring for 72 hours the reaction mixture was cooled to -10 °C and stirred for another hours. Then the crystals were collected by filtration. This provided asenapine maleate orthorhombic form (224 g, 86%). XRPD: >95% orthorhombic form
- Example 6 Crystallization of batch C4 (orthorhombic polymorph) The procedure was as described under example 5 with 28.9 kg of asenapine free base.
- Example 9-15 Micronization of batches C1-C6 to give M1-M6
- micronization of crystals of asenapine maleate of the orthorhombic polymorph consistently takes place with retention of the polymorphic form. This is evidenced by the results of the micronization of batches C3-C5, which furnished the micronized batches M4, M5, M6, and M7 (examples 12-15).
- the micronized batches M4-M7 all were characterized as the orthorhombic polymorph with a small particle i.e.: d95 ⁇ 30 ⁇ m, as is shown in Table 2.
- the polymorphic purity of the product is very high (>95% orthorhombic form) as substance of the monoclinic polymorph could not be detected by XRPD.
- Asenapine maleate of the orthorhombic form was mixed into a gelatin/mannitol matrix and dosed by weight into pre-formed pockets.
- the matrix was frozen within the pockets by passage through a freeze tunnel.
- the frozen tablets were then dried by sublimating the ice in a freeze dryer.
- Each pocket contained a pharmaceutical unit dosage comprising 7.03 mg of trans-S-chloro ⁇ S.Sa ⁇ b-tetrahydro ⁇ -methyl-I H-dibenz [2,3:6,7] oxepino [4,5-c] pyrrole (Z)-2-butenedioate, 10.0 mg gelatin and 7.5 mg mannitol.
- Example 17 Recrystallization to obtain orthorhombic form
- Asenapine maleate was isolated by filtration and washed with a 1 :1 mixture of acetone and heptane (30 kg) cooled to 10°C. The material was thereafter dried. The yield was 90-96%. XPRD analysis showed that >95% orthorhombic form was obtained.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL06725622T PL1917267T3 (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
BRPI0609741A BRPI0609741A8 (en) | 2005-04-07 | 2006-04-06 | compound, method of preparation and use thereof, pharmaceutical composition, and method for treating mental disorders in a mammal. |
NZ562124A NZ562124A (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
DE602006004463T DE602006004463D1 (en) | 2005-04-07 | 2006-04-06 | CRYSTAL FORM OF ASENAPINMALEATE |
CA2603509A CA2603509C (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
EP06725622A EP1917267B1 (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
AU2006231617A AU2006231617B2 (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
MX2007012445A MX2007012445A (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate. |
DK06725622T DK1917267T3 (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
KR1020077025428A KR101422843B1 (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
JP2008504776A JP5058151B2 (en) | 2005-04-07 | 2006-04-06 | Crystalline form of asenapine maleate |
IL186355A IL186355A (en) | 2005-04-07 | 2007-10-07 | Crystal form of asenapine maleate, a method for the preparation thereof, pharmaceutical composition comprising it, uses thereof in the preparation of pharmaceutical formulations for the treatment of mental disorders such as schizophrenia or bipolar disorder and microcrystalline form thereof |
NO20075142A NO340520B1 (en) | 2005-04-07 | 2007-10-10 | Crystal form of asenapine maleate, process for the preparation of such, pharmaceutical compositions comprising such and the use thereof for the treatment of disease |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP05102742.3 | 2005-04-07 | ||
EP05102742 | 2005-04-07 | ||
EP05102969.2 | 2005-04-14 | ||
EP05102969 | 2005-04-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006106135A1 true WO2006106135A1 (en) | 2006-10-12 |
Family
ID=36617328
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2006/061408 WO2006106135A1 (en) | 2005-04-07 | 2006-04-06 | Crystal form of asenapine maleate |
Country Status (31)
Country | Link |
---|---|
EP (2) | EP1917267B1 (en) |
JP (1) | JP5058151B2 (en) |
KR (1) | KR101422843B1 (en) |
AR (1) | AR056306A1 (en) |
AT (2) | ATE418556T1 (en) |
AU (1) | AU2006231617B2 (en) |
BR (1) | BRPI0609741A8 (en) |
CA (1) | CA2603509C (en) |
CY (2) | CY1106902T1 (en) |
DE (2) | DE602006004463D1 (en) |
DK (2) | DK1710245T3 (en) |
DO (1) | DOP2006000082A (en) |
ES (2) | ES2293626T3 (en) |
GT (1) | GT200600135A (en) |
HN (1) | HN2006014095A (en) |
HR (1) | HRP20070429T3 (en) |
IL (1) | IL186355A (en) |
MX (1) | MX2007012445A (en) |
MY (1) | MY137969A (en) |
NO (1) | NO340520B1 (en) |
NZ (1) | NZ562124A (en) |
PE (1) | PE20061311A1 (en) |
PL (2) | PL1917267T3 (en) |
PT (2) | PT1917267E (en) |
RS (1) | RS50532B (en) |
RU (1) | RU2405786C2 (en) |
SI (2) | SI1917267T1 (en) |
SV (1) | SV2006002473A (en) |
TW (1) | TWI364423B (en) |
UY (1) | UY29459A1 (en) |
WO (1) | WO2006106135A1 (en) |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008040816A1 (en) * | 2006-10-06 | 2008-04-10 | N.V. Organon | Amorphous asenapine and processes for preparing same |
WO2012080195A2 (en) | 2010-12-13 | 2012-06-21 | Chemo Iberica, S.A. | Polymorphic forms of asenapine maleate and processes for their preparation |
WO2012066565A3 (en) * | 2010-11-16 | 2012-07-26 | Cadila Healthcare Limited | Asenapine maleate amorphous and crystalline form and process for preparation thereof |
EP2524920A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel Crystalline Asenapine Hydrochloride Salt Forms |
EP2524919A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel crystalline salts of Asenapine with organic Di-acids and Tri-acids |
EP2524921A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel Crystalline Salts of Asenapine |
WO2012156676A1 (en) * | 2011-05-18 | 2012-11-22 | Laboratorios Lesvi S.L. | Monoclinic crystalline form of asenapine maleate with a specific particle size distribution |
WO2012156677A1 (en) * | 2011-05-18 | 2012-11-22 | Laboratorios Lesvi S.L. | A stable micronised monoclinic form of asenapine maleate and its synthesis |
EP2572703A1 (en) | 2011-09-21 | 2013-03-27 | Hexal AG | Compressed oral dosage form for asenapine maleate |
WO2013041604A1 (en) | 2011-09-21 | 2013-03-28 | Sandoz Ag | Crystal form of asenapine maleate |
EP2582704A2 (en) * | 2010-06-18 | 2013-04-24 | Dr. Reddy's Laboratories Ltd. | Asenapine maleate |
WO2014064076A1 (en) | 2012-10-24 | 2014-05-01 | Chemo Iberica, S.A. | Process for the preparation of a polymorph of asenapine maleate |
US10898449B2 (en) | 2016-12-20 | 2021-01-26 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
US11033512B2 (en) | 2017-06-26 | 2021-06-15 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine and silicone acrylic hybrid polymer |
US11337932B2 (en) | 2016-12-20 | 2022-05-24 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene |
US11648213B2 (en) | 2018-06-20 | 2023-05-16 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2453870A2 (en) * | 2009-06-24 | 2012-05-23 | MSD Oss B.V. | Injectable formulations containing asenapine and method of treatment using same |
WO2012123325A1 (en) | 2011-03-11 | 2012-09-20 | Medichem S.A. | NEW CRYSTAL FORMS OF THE SALT OF TRANS-5-CHLORO-2-METHYL-2,3,3A,12b-TETRAHYDRO-1H-DIBENZO[2,3:6,7]OXEPINO[4,5-c]PYRROLE WITH MALEIC ACID |
ITMI20110734A1 (en) * | 2011-05-02 | 2012-11-03 | Olon Spa | CRYSTALLINE ASENAPINE SALTS |
KR102013478B1 (en) * | 2012-07-26 | 2019-08-22 | 히사미쓰 세이야꾸 가부시키가이샤 | Patch |
WO2014090386A1 (en) | 2012-12-11 | 2014-06-19 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | Orally disintegrating tablet containing asenapine |
WO2014127786A1 (en) | 2013-02-22 | 2014-08-28 | Zentiva, K.S. | Orally disintegrating pharmaceutical composition comprising asenapine |
US10786520B2 (en) | 2015-09-02 | 2020-09-29 | Eloxx Pharmaceuticals Ltd. | Aminoglycoside derivatives and uses thereof in treating genetic disorders |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4145434A (en) * | 1976-05-24 | 1979-03-20 | Akzona Incorporated | Tetracyclic derivatives and pharmaceutical compositions of matter |
US5763476A (en) * | 1994-03-02 | 1998-06-09 | Akzo Noble N.V. | Sublingual or buccal pharmaceutical composition |
WO2004110437A1 (en) * | 2003-06-12 | 2004-12-23 | Organon Ireland Ltd. | Asenapine for the treatment of schizophrenia in a patient with overweight or predisposition for overweight |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999032108A1 (en) * | 1997-12-19 | 1999-07-01 | Akzo Nobel N.V. | Org-5222 in the treatment of depression |
-
2006
- 2006-04-06 GT GT200600135A patent/GT200600135A/en unknown
- 2006-04-06 MX MX2007012445A patent/MX2007012445A/en active IP Right Grant
- 2006-04-06 SV SV2006002473A patent/SV2006002473A/en unknown
- 2006-04-06 ES ES06112332T patent/ES2293626T3/en active Active
- 2006-04-06 AT AT06725622T patent/ATE418556T1/en active
- 2006-04-06 NZ NZ562124A patent/NZ562124A/en unknown
- 2006-04-06 TW TW095112187A patent/TWI364423B/en active
- 2006-04-06 EP EP06725622A patent/EP1917267B1/en active Active
- 2006-04-06 AT AT06112332T patent/ATE370954T1/en active
- 2006-04-06 PL PL06725622T patent/PL1917267T3/en unknown
- 2006-04-06 PE PE2006000377A patent/PE20061311A1/en active IP Right Grant
- 2006-04-06 DK DK06112332T patent/DK1710245T3/en active
- 2006-04-06 PT PT06725622T patent/PT1917267E/en unknown
- 2006-04-06 AU AU2006231617A patent/AU2006231617B2/en active Active
- 2006-04-06 PL PL06112332T patent/PL1710245T3/en unknown
- 2006-04-06 PT PT06112332T patent/PT1710245E/en unknown
- 2006-04-06 DE DE602006004463T patent/DE602006004463D1/en active Active
- 2006-04-06 ES ES06725622T patent/ES2318742T3/en active Active
- 2006-04-06 WO PCT/EP2006/061408 patent/WO2006106135A1/en active Application Filing
- 2006-04-06 SI SI200630190T patent/SI1917267T1/en unknown
- 2006-04-06 CA CA2603509A patent/CA2603509C/en active Active
- 2006-04-06 DO DO2006P000082A patent/DOP2006000082A/en unknown
- 2006-04-06 KR KR1020077025428A patent/KR101422843B1/en active IP Right Grant
- 2006-04-06 EP EP06112332A patent/EP1710245B1/en active Active
- 2006-04-06 JP JP2008504776A patent/JP5058151B2/en active Active
- 2006-04-06 BR BRPI0609741A patent/BRPI0609741A8/en not_active IP Right Cessation
- 2006-04-06 RS RSP-2007/0436A patent/RS50532B/en unknown
- 2006-04-06 MY MYPI20061554A patent/MY137969A/en unknown
- 2006-04-06 UY UY29459A patent/UY29459A1/en not_active Application Discontinuation
- 2006-04-06 RU RU2007141198/04A patent/RU2405786C2/en active Protection Beyond IP Right Term
- 2006-04-06 SI SI200630006T patent/SI1710245T1/en unknown
- 2006-04-06 DK DK06725622T patent/DK1917267T3/en active
- 2006-04-06 AR ARP060101358A patent/AR056306A1/en not_active Application Discontinuation
- 2006-04-06 HN HN2006014095A patent/HN2006014095A/en unknown
- 2006-04-06 DE DE602006000080T patent/DE602006000080T2/en active Active
-
2007
- 2007-09-19 HR HR20070429T patent/HRP20070429T3/en unknown
- 2007-10-02 CY CY20071101258T patent/CY1106902T1/en unknown
- 2007-10-07 IL IL186355A patent/IL186355A/en active IP Right Grant
- 2007-10-10 NO NO20075142A patent/NO340520B1/en unknown
-
2009
- 2009-01-30 CY CY20091100111T patent/CY1108742T1/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4145434A (en) * | 1976-05-24 | 1979-03-20 | Akzona Incorporated | Tetracyclic derivatives and pharmaceutical compositions of matter |
US5763476A (en) * | 1994-03-02 | 1998-06-09 | Akzo Noble N.V. | Sublingual or buccal pharmaceutical composition |
WO2004110437A1 (en) * | 2003-06-12 | 2004-12-23 | Organon Ireland Ltd. | Asenapine for the treatment of schizophrenia in a patient with overweight or predisposition for overweight |
Non-Patent Citations (2)
Title |
---|
FUNKE C W ET AL: "PHYSICO-CHEMICAL PROPERTIES AND STABILITY OF TRANS-5-CHLORO-2- METHYL-2,3,3A, 12B-TETRAHYDRO-1H-DIBENZ-2,3:6,70 OXEPINO-4,5-C) PYRROLIDINE MALEATE", ARZNEIMITTEL FORSCHUNG. DRUG RESEARCH, ECV EDITIO CANTOR VERLAG, AULENDORF, DE, vol. 40, no. 5, 1 May 1990 (1990-05-01), pages 536 - 539, XP000561359, ISSN: 0004-4172 * |
VADER J ET AL: "THE SYNTHESES OF RADIOLABELLED ORG 5222 AND ITS MAIN METABOLITE ORG 30526", JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, JOHN WILEY, CHICHESTER, GB, vol. 34, no. 9, 1994, pages 845 - 869, XP008058294, ISSN: 0362-4803 * |
Cited By (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008040816A1 (en) * | 2006-10-06 | 2008-04-10 | N.V. Organon | Amorphous asenapine and processes for preparing same |
EP2582704A4 (en) * | 2010-06-18 | 2014-04-02 | Reddys Lab Ltd Dr | Asenapine maleate |
US8779161B2 (en) | 2010-06-18 | 2014-07-15 | Dr. Reddy's Laboratories Limited | Asenapine maleate |
EP2582704A2 (en) * | 2010-06-18 | 2013-04-24 | Dr. Reddy's Laboratories Ltd. | Asenapine maleate |
WO2012066565A3 (en) * | 2010-11-16 | 2012-07-26 | Cadila Healthcare Limited | Asenapine maleate amorphous and crystalline form and process for preparation thereof |
US8933114B2 (en) | 2010-12-13 | 2015-01-13 | Chemo Iberica, S.A. | Polymorphic forms of asenapine maleate and processes for their preparation |
WO2012080195A2 (en) | 2010-12-13 | 2012-06-21 | Chemo Iberica, S.A. | Polymorphic forms of asenapine maleate and processes for their preparation |
EP2468750A1 (en) | 2010-12-13 | 2012-06-27 | Chemo Ibérica, S.A. | Polymorphic forms of asenapine maleate and processes for their preparation |
EP2524921A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel Crystalline Salts of Asenapine |
WO2012156383A1 (en) | 2011-05-17 | 2012-11-22 | Sandoz Ag | Novel crystalline salts of asenapine with organic di-acids and tri-acids |
WO2012156384A1 (en) | 2011-05-17 | 2012-11-22 | Sandoz Ag | Novel crystalline salts of asenapine |
US9169262B2 (en) | 2011-05-17 | 2015-10-27 | Sandoz Ag | Crystalline salts of Asenapine with organic di-acids and tri-acids |
WO2012156382A1 (en) | 2011-05-17 | 2012-11-22 | Sandoz Ag | Novel crystalline asenapine hydrochloride salt forms |
EP2524919A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel crystalline salts of Asenapine with organic Di-acids and Tri-acids |
EP2524920A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel Crystalline Asenapine Hydrochloride Salt Forms |
WO2012156676A1 (en) * | 2011-05-18 | 2012-11-22 | Laboratorios Lesvi S.L. | Monoclinic crystalline form of asenapine maleate with a specific particle size distribution |
WO2012156677A1 (en) * | 2011-05-18 | 2012-11-22 | Laboratorios Lesvi S.L. | A stable micronised monoclinic form of asenapine maleate and its synthesis |
US9533994B2 (en) | 2011-05-18 | 2017-01-03 | Laboratorios Lesvi S.L. | Monoclinic crystalline form of asenapine maleate with a specific particle size distribution |
JP2014513712A (en) * | 2011-05-18 | 2014-06-05 | ラビラトリオス レスビ エス エレ | Compound polymorphs |
US9505771B2 (en) | 2011-05-18 | 2016-11-29 | Laboratories Lesvi S.L. | Stable micronised monoclin form of asenapine maleate and its synthesis |
WO2013041435A1 (en) | 2011-09-21 | 2013-03-28 | Hexal Ag | Compressed oral dosage form for asenapine maleate |
EP2572703A1 (en) | 2011-09-21 | 2013-03-27 | Hexal AG | Compressed oral dosage form for asenapine maleate |
WO2013041604A1 (en) | 2011-09-21 | 2013-03-28 | Sandoz Ag | Crystal form of asenapine maleate |
WO2014064076A1 (en) | 2012-10-24 | 2014-05-01 | Chemo Iberica, S.A. | Process for the preparation of a polymorph of asenapine maleate |
US10898449B2 (en) | 2016-12-20 | 2021-01-26 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
US10980753B2 (en) | 2016-12-20 | 2021-04-20 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
US11337932B2 (en) | 2016-12-20 | 2022-05-24 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene |
US11033512B2 (en) | 2017-06-26 | 2021-06-15 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine and silicone acrylic hybrid polymer |
US11648213B2 (en) | 2018-06-20 | 2023-05-16 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2603509C (en) | Crystal form of asenapine maleate | |
US7741358B2 (en) | Crystal form of asenapine maleate | |
CN1861604B (en) | Crystal form of asenapine maleate | |
EP1799633B1 (en) | Crystalline forms of (-)-(1r,2r)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride for use as active ingredient in pharmaceutical compositions | |
JP4414237B2 (en) | Crystal form of quetiapine hemifumarate | |
AU2018259089B2 (en) | Polymorphs and solid forms of (s)-2-((2-((s)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo(ƒ)imidazo(1,2-d)(1,4)oxazepin-9-yl)amino)propanamide, and methods of production | |
WO2012123325A1 (en) | NEW CRYSTAL FORMS OF THE SALT OF TRANS-5-CHLORO-2-METHYL-2,3,3A,12b-TETRAHYDRO-1H-DIBENZO[2,3:6,7]OXEPINO[4,5-c]PYRROLE WITH MALEIC ACID | |
UA124728C2 (en) | Crystalline fumarate salt of (s)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone | |
US9127018B2 (en) | Solid forms of ortataxel | |
CN114773211B (en) | Meglumine salt crystal form, preparation method and application thereof | |
EP3960742A1 (en) | Crystals of alkynyl-containing compound, salt and solvate thereof, preparation method, and applications | |
CN116041323A (en) | Acid salt of Sigma-1 receptor agonist, crystal form thereof, preparation method and application thereof | |
WO2011039670A1 (en) | Novel forms of (2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b] indole) | |
EP2477960A1 (en) | Crystalline modifications of 6-dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexane-1,3-diol |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 562124 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2603509 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12007502177 Country of ref document: PH |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/a/2007/012445 Country of ref document: MX Ref document number: 2008504776 Country of ref document: JP Ref document number: 07104772 Country of ref document: CO |
|
WWE | Wipo information: entry into national phase |
Ref document number: 186355 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 4427/CHENP/2007 Country of ref document: IN |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006231617 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2006231617 Country of ref document: AU Date of ref document: 20060406 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020077025428 Country of ref document: KR |
|
WWP | Wipo information: published in national office |
Ref document number: 2006231617 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1200702316 Country of ref document: VN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007141198 Country of ref document: RU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006725622 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2006725622 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: PI0609741 Country of ref document: BR Kind code of ref document: A2 |