WO2014136122A1 - Process for the preparation of rotigotine polymorphic form-i - Google Patents

Process for the preparation of rotigotine polymorphic form-i Download PDF

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Publication number
WO2014136122A1
WO2014136122A1 PCT/IN2014/000139 IN2014000139W WO2014136122A1 WO 2014136122 A1 WO2014136122 A1 WO 2014136122A1 IN 2014000139 W IN2014000139 W IN 2014000139W WO 2014136122 A1 WO2014136122 A1 WO 2014136122A1
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Prior art keywords
rotigotine
rpm
minutes
solution
preparation
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PCT/IN2014/000139
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French (fr)
Inventor
Ramakoteswara Rao Jetti
Balakrishna Reddy Bhogala
Anjaneyaraju Indukuri
Angi Ramireddy BOMMAREDDY
Sreenivasa Rao Pathuri
Ramesh Kumar SABBAM
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Mylan Laboratories Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the present invention relates to an improved process for the preparation of rotigotine form-l, wherein the improvement comprises the use of seed material and reaction conditions.
  • Rotigotine is a non-ergolinic dopamine agonist and is marketed under the brand name NEUPRO®.
  • Neupro® is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease. It is formulated as 10 cm 2 , 20cm 2 , 30 cm 2 and 40 cm 2 transdermal patches containing respectively 4.5 mg, 9.0 mg, 13.5 mg and 18.0 mg of rotigotine and is designed to release respectively 2 mg, 4 mg, 6 mg, and 8 mg of rotigotine per 24 hours.
  • Rotigotine, (6S)-6-(propyl-(2-thiophen-2-ylethyl) amino) tetralin-1-ol has the following structure:
  • U.S. Patent Number 4,657,925 discloses the levo isomer of 2(N-propyl-N-2-thienylethyl-amino)-5- hydroxy tetralin (Rotigotine).
  • U.S. Patent Number 4,564,628 discloses a process for the preparation of rotigotine and pharmaceutically acceptable salts thereof, which involves the condensation of 5-methoxy tetralone with n-propylamine followed by reduction with PtO ⁇ yields 5- methoxy-2(N-propylamino)tetralin, which is further reacted with 2-thiophene acetic acid in the presence of trimethylamineborane in dry xylene followed by demethylation of thus formed 5- methoxy-2-(N-n-propyl-N-2-thienylethyl)-aminotetralin in the presence of HBr/BBr3 in dichloromethane.
  • the stepwise process is as shown in the scheme-l given below:
  • U.S. Patent Number 8,232,414 discloses a process for the preparation of rotigotine form-ll, wherein an ethanolic slurry of rotigotine form-l is spiked with seeds of rotigotine form-ll.
  • U.S. Patent Number 8,344, 165 discloses a process for the preparation of rotigotine form-l, wherein crude rotigotine is crystallized from hydrocarbon solvent, preferably n-hexane, to give rotigotine form-l.
  • the present invention relates to a process for the preparation of rotigotine form-l, wherein rotigotine is dissolved in a hydrocarbon solvent, the resulting solution is cooled to room temperature, followed by form-l seed to get crystalline rotigotine form-l. Temperature and rpm are the critical parameters for this process and it is feasible in large scale production with high yield.
  • the present aspect of the invention is to provide an improved process for the preparation of rotigotine form-l comprising the steps of;
  • step d) gradually cooling the step d) mixture to 0-5°C with 170- 90 rpm
  • the present invention relates to a process for the preparation of rotigotine form-l, wherein rotigotine is dissolved in a solvent and the resulting solution is cooled to room temperature with specific rpm, the resulting solution is seeded with form-l to get crystalline rotigotine form-l.
  • Main embodiment of the present invention is to provide an improved process for the preparation of rotigotine form-l comprising the steps of;
  • step d) gradually cooling the step d) mixture to 0-5°C with 170-190 rpm
  • rotigotine is dissolved in a hydrocarbon solvent at 80-90°C and undissolved particulates are filtered through a high-flow bed and the rpm (rotations per minute) are maintained by stirring at 80-90°C for about 1-3 hours.
  • the solution is slowly cooled to 25-32°C at the same rpm (50-70) and then pure form-l rotigotine crystals are added to the solution which is immediately increased to240-260 rpm and the stirring is maintained at 20-25°C for about 30minut.es to 1 hour.
  • the hydrocarbon solvent is selected from methyl cyclohexane, cyclohexane, n-heptane, pentane, cyclopentane or mixtures thereof.
  • rpm stirring and temperatures are critical operations to obtain good yield and purity.
  • the present process is optimized for high yield when the rpm is increased to 240-260 after seeding. This process is viable in large scale production.
  • Rotigotine 100gm was dissolved in methylcyclohexane (lOOOmL) at 80-90 °C.
  • the resulting solution was filtered into another flask at 60-65 °C and washed with hot methylcyclohexane (400 mL).
  • the solution was heated to 80-90 °C and maintained for 1-2 hours at 80-90 °C and allowed to cool at 20-22 °C in 15-45 minutes.
  • low rpm with 60-70 was maintained and added rotigotine form-l seeds (250mg) at 25-32°C. After seeding the rpm was raised immediately to 240-260 and maintained the stirring at 20-22°C for 20-30minutes.
  • Rotigotine hydrochloride (10gm) was taken in purified water (70mL), sodium bicarbonate (3.6gm) and methylcyclohexane (100mL) was added at 25-30 °C and heated to 85 ⁇ 5 °C for 1-2 hours. The reaction mass was settled in hot condition to separate the methylcyclohexane layer. To this layer added activated carbon and heated to 85 ⁇ 5 °C for 15-30 minutes. The resultant mass was filtered through hy-flo bed, washed with hot methyl cyclohexane (50 mL). The obtained filtrate was heated to 85 ⁇ 5 °C and maintained for 1-2 hours and then cooled to 20-22 °C in 15-45 minutes.
  • Rotigotine (10gm) was dissolved in methyl cyclohexane (150mL) at 85 ⁇ 5°C.
  • the resulting hot solution was filtered through hyflo-bed to remove any undissloved particles.
  • the obtained filtrate was heated to stir at 85 ⁇ 5°C for 1-2 hours and then cooled to 30-35°C, added rotigotine form-l seeds (25mg) at same temperature.
  • the reaction mass was allowed to cool at 20-25°C, stir for 30 minutes at same temperature and then cooled to 10-15°C, stir for 15 minutes at same temperature; further cooled to 0-5°C and stirred condition for 1 hour at same temperature.
  • the resultant slurry was filtered, washed with methyl cyclohexane (20mL) and suck dried for 30 minutes to obtain rotigotine form-l.
  • Rotigotine (10gm) and 3-Thiophene rotigotine impurity (15mg) was dissolved in methyl cyclohexane (. 50mL). a 85 ⁇ 5 0 C- The resulting- hot solution was filtered through hyflo-bed to remove any undissolved particles. The obtained filtrate was heated to 85 ⁇ 5°C and maintained for 1-2 hours and then allow to cooled at 20-25°C. While cooling the reaction mass, added rotigotine form-l seeds (25mg) at 30-35 °C. Maintained the reaction mass at 20-25°C for 30 minutes, then cool to 10-15°C and stirred the reaction mass for 15 minutes at same temperature; further cooled to 0-5°C and stirred for 1 hour at same temperature. The resultant slurry was filtered, washed with methyl cyclohexane (20ml) and suck dried for 30 minutes to obtain rotigotine form-l.
  • Rotigotine form II (15gm) was dissolved in methylcyclohexane (105mL) and then heated to reflux at 100 °C for 1hour to get clear solution.
  • the resulting solution was filtered into another flask at 70 - 80 °C and washed with hot methylcyclohexane (15 mL).
  • the solution was heated to reflux at 100 °C for 2hours and allowed to cool at 30 °C, added rotigotine form-l seeds (2mg).
  • the solution was cooled to 25 °C and stirred at same temperature for 30 minutes; further cooled the slurry at 0 °C and stirred for 2.5 hours at 0 - 5 °C.
  • the resultant solid was filtered and dried under vacuum for 30 minutes to obtain rotigotine form-l.
  • Rotigotine hydrochloride (10gm) was taken in purified water (70mL), sodium bicarbonate (3.6gm) and methyl cyclohexane (100mL) was added at room temperature and then heated to 85 ⁇ 5°C for 1-2 hours. The reaction mass was settled in hot condition to separate the methylcyclohexane layer. To this layer added activated carbon and allowed to heat at 85 ⁇ 5°C for 15-30 minutes; resultant mass was filtered through hy-flo bed, washed with hot methyl cyclohexane (50 mL). The obtained filtrate was heated to 85 ⁇ 5°C and maintained for 1-2 hours and then allow to cooled at 20-25°C.
  • Rotigotine hydrochloride (10gm) was taken in purified water_(70mL), -sodium bicarbonate (3.6gm) and methyl cyclohexane (100mL) was added at room temperature and then heated to 85 ⁇ 5°C for 1-2 hours. The reaction mass was settled in hot condition to separate the methylcyclohexane layer. To this layer added 3-Thiophene rotigotine impurity (13 mg), followed by activated carbon and allowed to heat at 85 ⁇ 5°C for 15-30 minutes; resultant mass was filtered through hy-flo bed, washed with hot methyl cyclohexane (50 mL).
  • the obtained filtrate was heated to 85 ⁇ 5°C and maintained for 1-2 hours and then allow to cooled at 20-25°C. While cooling the reaction mass, added rotigotine form-l seeds (25mg) at 30-35 °C. Maintained the reaction mass at 20-25°C for 30 minutes, then cool to 10-15°C and stirred the reaction mass for 15 minutes at same temperature. The reaction mass was further cooled to 0-5°C and stirred for 1 hour at same temperature. The resultant slurry was filtered, washed with methyl cyclohexane (20mL) and suck dried for 30 minutes to obtain rotigotine form-l.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to an improved process for the preparation of rotigotine form-l, wherein the improvement comprises the use of seed material under specified reaction conditions.

Description

PROCESS FOR THE PREPARATION OF ROTIGOTINE POLYMORPHIC FORM-I
This application claims priority from-lndian-patent application-926/CHE/2013 filed on March 01 , 2012 in its entirety.
FIELD OF THE INVENTION:
The present invention relates to an improved process for the preparation of rotigotine form-l, wherein the improvement comprises the use of seed material and reaction conditions.
BACKGROUND:
Rotigotine is a non-ergolinic dopamine agonist and is marketed under the brand name NEUPRO®. Neupro® is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease. It is formulated as 10 cm2, 20cm2, 30 cm2 and 40 cm2 transdermal patches containing respectively 4.5 mg, 9.0 mg, 13.5 mg and 18.0 mg of rotigotine and is designed to release respectively 2 mg, 4 mg, 6 mg, and 8 mg of rotigotine per 24 hours. Rotigotine, (6S)-6-(propyl-(2-thiophen-2-ylethyl) amino) tetralin-1-ol has the following structure:
^
Figure imgf000002_0001
Formula I
U.S. Patent Number 4,657,925 discloses the levo isomer of 2(N-propyl-N-2-thienylethyl-amino)-5- hydroxy tetralin (Rotigotine). U.S. Patent Number 4,564,628 discloses a process for the preparation of rotigotine and pharmaceutically acceptable salts thereof, which involves the condensation of 5-methoxy tetralone with n-propylamine followed by reduction with PtO∑ yields 5- methoxy-2(N-propylamino)tetralin, which is further reacted with 2-thiophene acetic acid in the presence of trimethylamineborane in dry xylene followed by demethylation of thus formed 5- methoxy-2-(N-n-propyl-N-2-thienylethyl)-aminotetralin in the presence of HBr/BBr3 in dichloromethane. The stepwise process is as shown in the scheme-l given below:
Figure imgf000003_0001
U.S. Patent Number 8,232,414 discloses a process for the preparation of rotigotine form-ll, wherein an ethanolic slurry of rotigotine form-l is spiked with seeds of rotigotine form-ll. U.S. Patent Number 8,344, 165 discloses a process for the preparation of rotigotine form-l, wherein crude rotigotine is crystallized from hydrocarbon solvent, preferably n-hexane, to give rotigotine form-l.
The present invention relates to a process for the preparation of rotigotine form-l, wherein rotigotine is dissolved in a hydrocarbon solvent, the resulting solution is cooled to room temperature, followed by form-l seed to get crystalline rotigotine form-l. Temperature and rpm are the critical parameters for this process and it is feasible in large scale production with high yield.
SUMMARY:
The present aspect of the invention is to provide an improved process for the preparation of rotigotine form-l comprising the steps of;
a) dissolving rotigotine in a hydrocarbon solvent at 80-90°C to form a solution,
b) cooling the solution slowly to 25-32°C with 60-70 rpm,
c) adding a seed crystals of rotigotine form-l at 25-32°C,
d) immediately raising the rpm to 240-260,
e) gradually cooling the step d) mixture to 0-5°C with 170- 90 rpm, and
f) isolating rotigotine form-l.
DETAILED DESCRIPTION:
The present invention relates to a process for the preparation of rotigotine form-l, wherein rotigotine is dissolved in a solvent and the resulting solution is cooled to room temperature with specific rpm, the resulting solution is seeded with form-l to get crystalline rotigotine form-l. Main embodiment of the present invention is to provide an improved process for the preparation of rotigotine form-l comprising the steps of;
a) dissolving rotigotine in a hydrocarbon-solvent at-80-90°G to form a solution, - b) cooling the solution slowly to 25-32°C with 60-70 rpm,
c) adding a seed crystals of rotigotine form-l at 25-32°C,
d) immediately raising the rpm to 240-260,
e) gradually cooling the step d) mixture to 0-5°C with 170-190 rpm, and
f) isolating rotigotine form-l.
According to the present invention, rotigotine is dissolved in a hydrocarbon solvent at 80-90°C and undissolved particulates are filtered through a high-flow bed and the rpm (rotations per minute) are maintained by stirring at 80-90°C for about 1-3 hours. The solution is slowly cooled to 25-32°C at the same rpm (50-70) and then pure form-l rotigotine crystals are added to the solution which is immediately increased to240-260 rpm and the stirring is maintained at 20-25°C for about 30minut.es to 1 hour. The resulting suspension is gradually cooled to 0-5°C with 170-190 rpm and the obtained solid is filtered and dried under vacuum at 20-30°C for 2-5 hours to obtain rotigotine Form-l. According to the present invention, the hydrocarbon solvent is selected from methyl cyclohexane, cyclohexane, n-heptane, pentane, cyclopentane or mixtures thereof.
According to the present invention, rpm stirring and temperatures are critical operations to obtain good yield and purity. The present process is optimized for high yield when the rpm is increased to 240-260 after seeding. This process is viable in large scale production.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the disclosure in any manner. Reasonable variations of the described procedures are intended to be within the scope of the present application. While particular aspects of the present application have been illustrated and described, it would be apparent to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the disclosure. It is therefore intended to encompass all such changes and modifications that are within the scope of this disclosure. Example 1
Rotigotine (100gm) was dissolved in methylcyclohexane (lOOOmL) at 80-90 °C. The resulting solution was filtered into another flask at 60-65 °C and washed with hot methylcyclohexane (400 mL). The solution was heated to 80-90 °C and maintained for 1-2 hours at 80-90 °C and allowed to cool at 20-22 °C in 15-45 minutes. While cooling, low rpm with 60-70 was maintained and added rotigotine form-l seeds (250mg) at 25-32°C. After seeding the rpm was raised immediately to 240-260 and maintained the stirring at 20-22°C for 20-30minutes. Cool the reaction mass to 0- 5°C in 30-60 minutes and maintained at 0-5°C for 1-3 hours with 170-190 rpm. The resulting solid was filtered and washed with chilled methyl cyclohexane (100 mL). Suck dried the material under vacuum for 30-60 minutes and dried under vacuum at 20-30°C for 2-5hours to obtain rotigotine Form-l.
Yield: 85 gm
Example 2
Rotigotine hydrochloride (10gm) was taken in purified water (70mL), sodium bicarbonate (3.6gm) and methylcyclohexane (100mL) was added at 25-30 °C and heated to 85±5 °C for 1-2 hours. The reaction mass was settled in hot condition to separate the methylcyclohexane layer. To this layer added activated carbon and heated to 85±5 °C for 15-30 minutes. The resultant mass was filtered through hy-flo bed, washed with hot methyl cyclohexane (50 mL). The obtained filtrate was heated to 85±5 °C and maintained for 1-2 hours and then cooled to 20-22 °C in 15-45 minutes. While cooling low rpm with 60-70 was maintained and added rotigotine form-l seeds (25mg) at 25-32°C. After seeding the rpm was raised immediately to 240-260 and maintained the stirring at 20-22°C for 20-30minutes. Cool the reaction mass to 0-5°C in 30-60 minutes and maintained at 0-5°C for 1-3 hours with 170-190 rpm. The resulting solid was filtered and washed with chilled methyl cyclohexane (20 mL). Suck dried the material under vacuum for 30-60 minutes and dried under vacuum at 20-30 °C for 2-5 hour to obtain rotigotine Form-l.
Example 3
Rotigotine (10gm) was dissolved in methyl cyclohexane (150mL) at 85±5°C. The resulting hot solution was filtered through hyflo-bed to remove any undissloved particles. The obtained filtrate was heated to stir at 85±5°C for 1-2 hours and then cooled to 30-35°C, added rotigotine form-l seeds (25mg) at same temperature. The reaction mass was allowed to cool at 20-25°C, stir for 30 minutes at same temperature and then cooled to 10-15°C, stir for 15 minutes at same temperature; further cooled to 0-5°C and stirred condition for 1 hour at same temperature. The resultant slurry was filtered, washed with methyl cyclohexane (20mL) and suck dried for 30 minutes to obtain rotigotine form-l.
Yield: 8-9gm Example 4
Rotigotine (10gm) and 3-Thiophene rotigotine impurity (15mg) was dissolved in methyl cyclohexane (. 50mL). a 85±50C- The resulting- hot solution was filtered through hyflo-bed to remove any undissolved particles. The obtained filtrate was heated to 85±5°C and maintained for 1-2 hours and then allow to cooled at 20-25°C. While cooling the reaction mass, added rotigotine form-l seeds (25mg) at 30-35 °C. Maintained the reaction mass at 20-25°C for 30 minutes, then cool to 10-15°C and stirred the reaction mass for 15 minutes at same temperature; further cooled to 0-5°C and stirred for 1 hour at same temperature. The resultant slurry was filtered, washed with methyl cyclohexane (20ml) and suck dried for 30 minutes to obtain rotigotine form-l.
Yield: 8-9gm
Example 5
Rotigotine form II (15gm) was dissolved in methylcyclohexane (105mL) and then heated to reflux at 100 °C for 1hour to get clear solution. The resulting solution was filtered into another flask at 70 - 80 °C and washed with hot methylcyclohexane (15 mL). The solution was heated to reflux at 100 °C for 2hours and allowed to cool at 30 °C, added rotigotine form-l seeds (2mg).The solution was cooled to 25 °C and stirred at same temperature for 30 minutes; further cooled the slurry at 0 °C and stirred for 2.5 hours at 0 - 5 °C. The resultant solid was filtered and dried under vacuum for 30 minutes to obtain rotigotine form-l.
Yield: 13.5gm
Example 6
Rotigotine hydrochloride (10gm) was taken in purified water (70mL), sodium bicarbonate (3.6gm) and methyl cyclohexane (100mL) was added at room temperature and then heated to 85±5°C for 1-2 hours. The reaction mass was settled in hot condition to separate the methylcyclohexane layer. To this layer added activated carbon and allowed to heat at 85±5°C for 15-30 minutes; resultant mass was filtered through hy-flo bed, washed with hot methyl cyclohexane (50 mL). The obtained filtrate was heated to 85±5°C and maintained for 1-2 hours and then allow to cooled at 20-25°C. While cooling the reaction mass, added rotigotine form-l seeds (25mg) at 30-35 °C. Maintained the reaction mass at 20-25°C for 30 minutes, then cool to 10-15°C and stirred the reaction mass for 15 minutes at same temperature; further cooled to 0-5°C and stirred for 1 hour at same temperature. The resultant slurry was filtered, washed with methyl cyclohexane (20mL) and suck dried for 30 minutes to obtain rotigotine form-l.
Yield: 7.0-7.5gm Example 7
Rotigotine hydrochloride (10gm) was taken in purified water_(70mL), -sodium bicarbonate (3.6gm) and methyl cyclohexane (100mL) was added at room temperature and then heated to 85±5°C for 1-2 hours. The reaction mass was settled in hot condition to separate the methylcyclohexane layer. To this layer added 3-Thiophene rotigotine impurity (13 mg), followed by activated carbon and allowed to heat at 85±5°C for 15-30 minutes; resultant mass was filtered through hy-flo bed, washed with hot methyl cyclohexane (50 mL). The obtained filtrate was heated to 85±5°C and maintained for 1-2 hours and then allow to cooled at 20-25°C. While cooling the reaction mass, added rotigotine form-l seeds (25mg) at 30-35 °C. Maintained the reaction mass at 20-25°C for 30 minutes, then cool to 10-15°C and stirred the reaction mass for 15 minutes at same temperature. The reaction mass was further cooled to 0-5°C and stirred for 1 hour at same temperature. The resultant slurry was filtered, washed with methyl cyclohexane (20mL) and suck dried for 30 minutes to obtain rotigotine form-l.
Yield: 7.0-7.5gm
Example 8
Sodium bicarbonate (26.8gm) was dissolved in water (525mL) and methylcyclohexane (525mL). To this mixture added 3-thiophenyl rotigotine isomer impurity (54mg), dithienylethyl rotigotine impurity (121mg) and rotigotine hydrochloride (75gm) was heated to stirred at 70 - 80 °C for 1.5 hours at same temperature to separate the methylcyclohexane layer. The organic layer was heated to reflux at 100°C for 30 minutes under slow stirred condition. The solution was cooled to 25 - 30 °C, followed by addition of rotigotine form-l seeds (10mg). Crystallization was started within 5 minutes and reaction mass was stirred for about 2 hours at same temperature. The reaction mass was further cooled to 0-5 °C and stirred for 2.5 hours; resultant slurry was filtered, washed with methyl cyclohexane (50mL) and suck dried for 30 minutes to obtain rotigotine form-l. Yield: 61gm

Claims

We claim:
1. An improved process for the preparation of rotigotine form-l comprising the steps of; a) dissolving rotigotine in a hydrocarbon solvent at 80-90°C to form a solution, b) cooling the solution slowly to 25-32°C with 60-70 rpm,
c) adding seed crystals of rotigotine form-l at 25-32°C to the cooled solution,
d) immediately raising the rpm to 240-260,
e) gradually cooling the solution to 0-5°C with 170-190 rpm, and
f) isolating rotigotine form-l.
2. The process according to claim 1 , wherein the hydrocarbon solvent is selected from methyl cyclohexane, cyclohexane, n-hexane, and heptane or mixtures thereof.
PCT/IN2014/000139 2013-03-04 2014-03-03 Process for the preparation of rotigotine polymorphic form-i WO2014136122A1 (en)

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IN926/CHE/2013 2013-03-04

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8232414B2 (en) * 2007-11-28 2012-07-31 Ucb Pharma Gmbh Polymorphic form of rotigotine and process for production
US8344165B2 (en) * 2007-05-30 2013-01-01 Chemagis Ltd. Crystalline rotigotine base and preparation process therefor

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8344165B2 (en) * 2007-05-30 2013-01-01 Chemagis Ltd. Crystalline rotigotine base and preparation process therefor
US8232414B2 (en) * 2007-11-28 2012-07-31 Ucb Pharma Gmbh Polymorphic form of rotigotine and process for production

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANDERSON ET AL.: "TOOLS FOR PURIFYING THE PRODUCT: COLUMN CHROMATOGRAPHY, CRYSTALLIZATION AND RESLURRYING", PRACTICAL PROCESS RESEARCH AND DEVELOPMENT, ACADEMIC PRESS, SAN DIEGO, US, 1 January 2000 (2000-01-01), pages 223 - 247, XP002382432 *
LEE ET AL.: "Crystal polymorphism in chemical process development", ANNU. REV. CHEM. BIOMOL. ENG., vol. 2, 1 January 2011 (2011-01-01), pages 259 - 280, XP009177161, ISSN: 1947-5438 *

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