WO2004089873A1 - Process for crystallising bupropion hydrochloride - Google Patents

Process for crystallising bupropion hydrochloride Download PDF

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Publication number
WO2004089873A1
WO2004089873A1 PCT/EP2004/050495 EP2004050495W WO2004089873A1 WO 2004089873 A1 WO2004089873 A1 WO 2004089873A1 EP 2004050495 W EP2004050495 W EP 2004050495W WO 2004089873 A1 WO2004089873 A1 WO 2004089873A1
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Prior art keywords
bupropion hydrochloride
precipitating solvent
product
mixture
cooled
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PCT/EP2004/050495
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French (fr)
Inventor
Massimo Ferrari
Florindo De Luca
Fiorella Lombardi
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Erregierre S.P.A.
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Priority to CA002549350A priority Critical patent/CA2549350A1/en
Publication of WO2004089873A1 publication Critical patent/WO2004089873A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton

Definitions

  • the present invention relates to a new process for crystallising Bupropion hydrochloride. This process enables Bupropion hydrochloride to be obtained in 5 the form of large crystals having a particle size distribution with D90% greater than 100 ⁇ m.
  • the particle size distribution of an active principle is a critical parameter in the production of solid and semi-solid pharmaceutical forms such as for example 0 tablets, capsules and suspensions.
  • the subdivision state of the active principle influences important properties both for technical purposes, for example flowing ability and compressibility, and for therapeutic purposes, in particular its dissolution rate and hence bio-availability.
  • Bupropion hydrochloride crystallisation conditions that allow said compound to be obtained in the form of o crystals with optimum dimensions and morphology for preparing pharmaceutical forms.
  • Bupropion hydrochloride obtained with the process of the present invention presents a particle size distribution with D90% greater than 100 ⁇ m.
  • FIGURES 5 Figure 1 shows an electron microscopic view of a Bupropion hydrochloride sample obtained with the method described in example 4.
  • Figure 2 shows an electron microscopic view of a Bupropion hydrochloride sample obtained with the method described in example 9.
  • Figures 3, 4 and 5 show electron microscopic views of samples of three different 0 batches (batch 1 , 2 and 3 respectively) of Bupropion hydrochloride obtained with the method described in example 17.
  • the present invention relates to a process for crystallising Bupropion hydrochloride comprising the following steps: a) Bupropion hydrochloride is dissolved in a mixture comprising methanol and a precipitating solvent for Bupropion hydrochloride; b) any insoluble residue is removed; c) the solution is distilled at atmospheric pressure until the precipitation reaction is triggered. d) the following are added: I) a precipitating solvent for Bupropion hydrochloride; and II) hydrochloric acid until a pH ⁇ 2 is obtained. e) the mass is cooled to a temperature less than 10°C, preferably between 0 and 3°C, and the precipitate obtained is separated.
  • the precipitate obtained is preferably washed with a precipitating solvent and dried at a temperature between 40 and 80°C.
  • the term "precipitating solvent” means a solvent in which Bupropion hydrochloride is insoluble even at temperatures greater that 60°C.
  • the same precipitating solvent is used in stages a) and d).
  • the precipitating solvents preferably used in the process of the present invention are chosen from the group consisting of C2 to C8 linear or branched alcohols, of which ethanol, 2-butanol and isopropyl alcohol are particularly preferred, acetone, acetonitrile, ethyl acetate, diglyme, toluene, 2-methoxyethanol (methyl cellosolve®) and dimethylformamide.
  • a particularly preferred precipitating solvent in the process of the present invention is 2-butanol.
  • methyl alcohol and precipitating solvent are in a ratio suitable to obtain the solubilisation of Bupropion hydrochloride.
  • the precipitating solvent is added in a quantity capable of achieving a precipitated mass with optimum operative characteristics.
  • the crystallisation process of the invention allows particles of Bupropion hydrochloride to be obtained having particle size distribution and morphology very different from those obtained using other crystallisation processes.
  • Bupropion hydrochloride with crystals of large dimensions (D90% greater than 100 ⁇ m) (examples 9 to 17) are obtained with the process of the invention, with other crystallisation processes (examples 1 to 8) a microcrystalline product is obtained.
  • Acetone 1000 g are fed into a 2 litre flask.
  • the mass is stirred at 20-30°C until dissolution is complete. Starting from this temperature and without exceeding 50°C, gaseous HCI is bubbled in until pH 2 is achieved. The precipitated mass is cooled to 0-3°C and filtered off, washing with
  • the wet product is dried at 70-80°C
  • the mixture is stirred at 60-65°C until dissolution is complete, cooled slowly to a temperature between 0 and 3°C and the precipitated mass is stirred at this temperature for about half an hour.
  • the product is then filtered off and washed with:
  • the wet product is dried at 70-80°C.
  • Dimethylformamide 160 g are fed into a 1 litre flask.
  • the wet product is dried at 70-80°C.
  • the mixture is stirred at 90-95°C until dissolution is complete. Then
  • Acetone 200 g is added. The mixture is slowly cooled to a temperature between 0 and 3°C and the crystallised product is filtered off and washed with: Acetone 90 g
  • the wet product is dried at 70-80°C.
  • 2-Butanol 150 g are fed into a 500 ml flask.
  • the mixture is stirred at 20-30°C until dissolution is complete. Without exceeding
  • the wet product is dried at 70-80°C.
  • Dimethylformamide 160 g are fed into a 250 ml flask.
  • the wet product is dried at 70-80°C.
  • Ethanol 100 g are fed into a 250 ml flask.
  • the wet product is dried at 70-80°C.
  • the wet product is dried at 70-80°C.
  • Isopropyl alcohol 80 g are fed into a 250 ml flask. 5 The mixture is stirred at 60-70°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
  • the wet product is dried at 70-80°C.
  • Acetone 80 g are fed into a 250 ml flask.
  • the mixture is stirred at 60-65°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
  • the wet product is dried at 70-80°C.
  • Bupropion hydrochloride 36.4 g are obtained and sifted with a 36 mesh sieve.
  • Diglyme 80 g are fed into a 250 ml flask.
  • the mixture is stirred at 50-55°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
  • the wet product is dried at 70-80°C.
  • Bupropion hydrochloride 36.4 g are obtained and sifted with a 36 mesh sieve.
  • Ethanol 80 g are fed into a 250 ml flask.
  • the mixture is stirred at 40-45°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
  • the wet product is dried at 70-80°C.
  • Toluene 80 g are fed into a 250 ml flask. The mixture is stirred at 40-45°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
  • the wet product is dried at 70-80°C. 35.5 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
  • Methyl cellosolve® 80 g are fed into a 250 ml flask.
  • the mixture is stirred at 35-40°C until dissolution is complete, then distilled at atmospheric pressure to 90°C.
  • the wet product is dried at 70-80°C. 27.8 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
  • Dimethylformamide 80 g are fed into a 250 ml flask.
  • the mixture is stirred at 35-40°C until dissolution is complete, then distilled at atmospheric pressure to 95°C.
  • the wet product is dried at 70-80°C. 27 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
  • Example 17 o The method described in example 9 was repeated on an industrial scale, using the following components:
  • Example 18 Samples of Bupropion hydrochloride obtained with the process described in example 4, example 5 or example 17 were analysed by electron microscopy (SEM analysis) under the following experimental conditions:

Abstract

Process for crystallising Bupropion hydrochloride comprising the following stages: a) Bupropion hydrochloride is dissolved in a mixture comprising methanol and a precipitating solvent for Bupropion hydrochloride; b) any insoluble residue is removed; c) the solution is distilled at atmospheric pressure until the precipitation reaction is triggered; d) the following are added: I) a precipitating solvent for Bupropion hydrochloride and II) hydrochloric acid until a pH ≤ 2 is obtained; e) the mass is cooled to a temperature less than 10° C, preferably between 0 and 3° C and the precipitate obtained is separated.

Description

PROCESS FOR CRYSTALLISING BUPROPION HYDROCHLORIDE
FIELD OF THE INVENTION
The present invention relates to a new process for crystallising Bupropion hydrochloride. This process enables Bupropion hydrochloride to be obtained in 5 the form of large crystals having a particle size distribution with D90% greater than 100 μm.
STATE OF THE ART
The particle size distribution of an active principle is a critical parameter in the production of solid and semi-solid pharmaceutical forms such as for example 0 tablets, capsules and suspensions. In this respect, the subdivision state of the active principle influences important properties both for technical purposes, for example flowing ability and compressibility, and for therapeutic purposes, in particular its dissolution rate and hence bio-availability.
It is therefore important to have processes available for preparing active principles s which enable such compositions with predefined particle sizes and suitable for preparing pharmaceutical forms to be obtained.
SUMMARY
The present inventors have found particular Bupropion hydrochloride crystallisation conditions that allow said compound to be obtained in the form of o crystals with optimum dimensions and morphology for preparing pharmaceutical forms. In particular, Bupropion hydrochloride obtained with the process of the present invention presents a particle size distribution with D90% greater than 100 μm.
DESCRIPTION OF THE FIGURES 5 Figure 1 shows an electron microscopic view of a Bupropion hydrochloride sample obtained with the method described in example 4.
Figure 2 shows an electron microscopic view of a Bupropion hydrochloride sample obtained with the method described in example 9.
Figures 3, 4 and 5 show electron microscopic views of samples of three different 0 batches (batch 1 , 2 and 3 respectively) of Bupropion hydrochloride obtained with the method described in example 17. DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a process for crystallising Bupropion hydrochloride comprising the following steps: a) Bupropion hydrochloride is dissolved in a mixture comprising methanol and a precipitating solvent for Bupropion hydrochloride; b) any insoluble residue is removed; c) the solution is distilled at atmospheric pressure until the precipitation reaction is triggered. d) the following are added: I) a precipitating solvent for Bupropion hydrochloride; and II) hydrochloric acid until a pH < 2 is obtained. e) the mass is cooled to a temperature less than 10°C, preferably between 0 and 3°C, and the precipitate obtained is separated.
The precipitate obtained is preferably washed with a precipitating solvent and dried at a temperature between 40 and 80°C.
For the purposes of the present invention, the term "precipitating solvent" means a solvent in which Bupropion hydrochloride is insoluble even at temperatures greater that 60°C. Preferably, the same precipitating solvent is used in stages a) and d). The precipitating solvents preferably used in the process of the present invention are chosen from the group consisting of C2 to C8 linear or branched alcohols, of which ethanol, 2-butanol and isopropyl alcohol are particularly preferred, acetone, acetonitrile, ethyl acetate, diglyme, toluene, 2-methoxyethanol (methyl cellosolve®) and dimethylformamide. A particularly preferred precipitating solvent in the process of the present invention is 2-butanol.
In the mixture of stage a), methyl alcohol and precipitating solvent are in a ratio suitable to obtain the solubilisation of Bupropion hydrochloride. In step d) the precipitating solvent is added in a quantity capable of achieving a precipitated mass with optimum operative characteristics. As will be illustrated in detail in the examples which follow, the crystallisation process of the invention allows particles of Bupropion hydrochloride to be obtained having particle size distribution and morphology very different from those obtained using other crystallisation processes. In particular, while Bupropion hydrochloride with crystals of large dimensions (D90% greater than 100μm) (examples 9 to 17) are obtained with the process of the invention, with other crystallisation processes (examples 1 to 8) a microcrystalline product is obtained.
The invention will now be illustrated by means of the following explanatory and non-limiting examples.
EXAMPLES
Example 1 Bupropion base 250 g
Acetone 1000 g are fed into a 2 litre flask.
The mass is stirred at 20-30°C until dissolution is complete. Starting from this temperature and without exceeding 50°C, gaseous HCI is bubbled in until pH 2 is achieved. The precipitated mass is cooled to 0-3°C and filtered off, washing with
250 g of acetone. The wet product is dried at 70-80°C. 240 g of crude Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 2
Crude Bupropion hydrochloride 40 g Dimethylformamide 160 g are fed into a 1 litre flask.
The mixture is stirred at 90-95°C until dissolution is complete. Then:
Ethyl acetate 200 g is added. At 75-80°C the product crystallises. The mixture is cooled slowly to a temperature between 0 and 3°C. Then the product is filtered off and washed with:
Ethyl acetate 90 g
The wet product is dried at 70-80°C
33 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve. Example 3
Crude Bupropion hydrochloride 40 g Methanol 40 g are fed into a 250 ml flask.
The mixture is stirred at 60-65°C until dissolution is complete, cooled slowly to a temperature between 0 and 3°C and the precipitated mass is stirred at this temperature for about half an hour. The product is then filtered off and washed with:
Methanol 20 g
The wet product is dried at 70-80°C.
22 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve. Example 4
Crude Bupropion hydrochloride 40 g
Dimethylformamide 160 g are fed into a 1 litre flask.
The mixture is stirred at 90-95°C until dissolution is complete. Then 2-Butanol 400 g is added
The mixture is cooled to a temperature between -2°C and +2°C and then stirred at this temperature until crystallisation is abundant. The product is filtered off and washed with: 2-Butanol 60 g
The wet product is dried at 70-80°C.
18 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 5
Crude Bupropion hydrochloride 40 g Dimethylformamide 160 g are fed into a 1 litre flask.
The mixture is stirred at 90-95°C until dissolution is complete. Then
Acetone 200 g is added. The mixture is slowly cooled to a temperature between 0 and 3°C and the crystallised product is filtered off and washed with: Acetone 90 g
The wet product is dried at 70-80°C.
30 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 6 Bupropion hydrochloride base 50 g
2-Butanol 150 g are fed into a 500 ml flask.
The mixture is stirred at 20-30°C until dissolution is complete. Without exceeding
50°C gaseous HCI is bubbled in until pH 1 is achieved. The crystallised product is slowly cooled to 0-5°C and is stirred at this temperature for about 1 hour. The product is filtered off and washed with:
2-Butanol 20 g
The wet product is dried at 70-80°C.
45 g Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve. Example 7
Crude Bupropion hydrochloride 40 g
Dimethylformamide 160 g are fed into a 250 ml flask.
The mixture is stirred at 90-95°C until dissolution is complete and cooled slowly to 0-2°C. The crystalline mass is then stirred at this temperature for about half an hour. The product is filtered off, washing with:
Ethyl acetate 60 g
The wet product is dried at 70-80°C.
25.5 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve. Example 8
Crude Bupropion hydrochloride 40 g
Ethanol 100 g are fed into a 250 ml flask.
The mixture is stirred at 70-75°C under reflux until dissolution is complete, cooled slowly to 0-2°C and stirred at this temperature for about half an hour. The product is filtered off, washing with: Ethanol 20 g
The wet product is dried at 70-80°C.
31 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
5 Example 9
Crude Bupropion hydrochloride 110 g
Methanol 150 g
2-Butanol 250.7 g are fed into a 1 litre flask. 0 The mixture is heated under reflux to 73-75°C until dissolution is complete. The solution is then filtered at this temperature and distilled at atmospheric pressure to
92-93°C, the temperature at which the product crystallises.
2-Butanol 125.3 g
37% Hydrochloric acid 0.8 g 5 are now added. The mass is cooled to 0-3°C, then the product is filtered off and washed with:
2-Butanol 141.4 g
The wet product is dried at 70-80°C.
107 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve. o Example 10
Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Isopropyl alcohol 80 g are fed into a 250 ml flask. 5 The mixture is stirred at 60-70°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
(maximum temperature reached is 75°C).
Isopropyl alcohol 50 g
37% Hydrochloric acid 0.4 g 0 are added while hot.
The mass is cooled to 0-3°C, then the product is filtered off and washed with Isopropyl alcohol 40 g
The wet product is dried at 70-80°C.
33 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 11 Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Acetone 80 g are fed into a 250 ml flask.
The mixture is stirred at 60-65°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
(maximum temperature reached is 67°C).
Acetone 50 g
37% Hydrochloric acid 0.4 g are added while hot. The mass is cooled to 0-3°C, then the product is filtered off and washed with
Acetone 40 g
The wet product is dried at 70-80°C.
36.4 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 12 Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Diglyme 80 g are fed into a 250 ml flask.
The mixture is stirred at 50-55°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
(maximum temperature reached is 85°C).
Diglyme 50 g
37% Hydrochloric acid 0.4% are added while hot. The mass is cooled to 0-3°C, then the product is filtered off and washed with:
Diglyme 20 g Acetone 40 g
The wet product is dried at 70-80°C.
36.4 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 13 Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Ethanol 80 g are fed into a 250 ml flask.
The mixture is stirred at 40-45°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
(maximum temperature reached is +79°C). After cooling to 30-40°C:
Ethanol 50 g
37% HCI 0.4 g are added. The mass is cooled to a temperature between 0 and 3°C, then the product is filtered off and washed with:
Ethanol 40 g
The wet product is dried at 70-80°C.
22 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve. Example 14
Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Toluene 80 g are fed into a 250 ml flask. The mixture is stirred at 40-45°C until dissolution is complete, then distilled at atmospheric pressure until precipitation is triggered and becomes abundant
(maximum temperature reached is +79°C).
Toluene 50 g
37% Hydrochloric acid 0.4 g are added while hot.
The mass is cooled to 0-3°C, then the product is filtered off and washed with: Toluene 40 g
The wet product is dried at 70-80°C. 35.5 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 15 Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Methyl cellosolve® 80 g are fed into a 250 ml flask.
The mixture is stirred at 35-40°C until dissolution is complete, then distilled at atmospheric pressure to 90°C.
Distillation is continued under slight vacuum until crystallisation is triggered.
Atmospheric pressure is restored and:
Methyl cellosolve® 50 g
37% Hydrochloric acid 0.4 g are added at 65°C.
The mass is cooled to 0-3°C, then the product is filtered off and washed with:
Methyl cellosolve® 20 g
Acetone 40 g
The wet product is dried at 70-80°C. 27.8 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 16
Crude Bupropion hydrochloride 40 g
Methyl alcohol 50 g
Dimethylformamide 80 g are fed into a 250 ml flask.
The mixture is stirred at 35-40°C until dissolution is complete, then distilled at atmospheric pressure to 95°C.
Distillation is continued under slight vacuum until crystallisation is triggered.
Atmospheric pressure is restored and: Dimethylformamide 50 g
37% Hydrochloric acid 0.4 g are added at 70°C.
The mass is cooled to a temperature between 0 and 3°C, then the product is filtered off and washed with: Dimethylformamide 20 g
5 Acetone 40 g
The wet product is dried at 70-80°C. 27 g of Bupropion hydrochloride are obtained and sifted with a 36 mesh sieve.
Example 17 o The method described in example 9 was repeated on an industrial scale, using the following components:
Figure imgf000011_0001
About 225 Kg of dry Bupropion hydrochloride were obtained.
Example 18 s Samples of Bupropion hydrochloride obtained with the process described in example 4, example 5 or example 17 were analysed by electron microscopy (SEM analysis) under the following experimental conditions:
Instrument: Cambridge Stereoscan 360
Operative Conditions: EHT 20.0 Kv, WD 10 mm, 200 X magnification. o The samples were placed on a bio-adhesive layer of graphite and covered with gold to make them conductive.
Results:
The product of example 4 (Fig. 1 ) shows microcrystalline agglomerates of an undefined structure, while the products obtained with the methods described in example 9 (Fig 2) or in example 17 (Figures 3, 4 and 5, which refer to three different batches) demonstrate tablet-like crystals of similar morphology and with probably similar monoclinic symmetry.
Example 19
The particle size distribution of the Bupropion hydrochloride crystals obtained with the processes described in examples 1 to 17 was analysed using the Malvern method.
The following results were obtained:
Figure imgf000012_0001
Figure imgf000013_0001
The results obtained demonstrate that only the particular crystallisation technique described in examples 9-17 allows Bupropion hydrochloride to be obtained in the form of crystals of large dimensions whereas with other crystallisation techniques, a product with a decidedly smaller particle size distribution is obtained.

Claims

1. Process for crystallising Bupropion hydrochloride comprising the following steps: a) Bupropion hydrochloride is dissolved in a mixture comprising methyl alcohol and a precipitating solvent for Bupropion hydrochloride; b) any insoluble residue is removed; c) the solution is distilled at atmospheric pressure until the precipitation reaction is triggered; d) the following are added: I) a precipitating solvent for Bupropion hydrochloride; and II) hydrochloric acid until a pH ≤ 2 is obtained; e) the mass is cooled to a temperature less than 10°C and the precipitate obtained is separated.
2. Process as claimed in claim 1 wherein the precipitate obtained in stage e) is washed with a precipitating solvent and dried at a temperature between 40 and
80°C.
3. Process as claimed in claim 1 or 2 wherein the product obtained is characterised by a particle size distribution with D90% greater than 100μm.
4. Process as claimed in claims 1 to 3 wherein said precipitating solvent is chosen from the group comprising C2 to C8 linear or branched alcohols, acetone, acetonitrile, ethyl acetate, diglyme, toluene, 2-methoxyethanol (methyl cellosolve®) and dimethylformamide.
5. Process as claimed in claim 4 wherein said alcohols are chosen from the group comprising ethanol, 2-butanol and propyl alcohol.
6. Process as claimed in claim 4 wherein said precipitating solvent is 2-butanol.
7. Process as claimed in claims 1 to 6 wherein the same precipitating solvent is used in stages a) and d).
PCT/EP2004/050495 2003-04-11 2004-04-09 Process for crystallising bupropion hydrochloride WO2004089873A1 (en)

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ITMI20030762 ITMI20030762A1 (en) 2003-04-11 2003-04-11 HYDROCHLORIDE BUPROPION CRYSTALLIZATION PROCESS.
ITMI2003A000762 2003-04-11

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Cited By (8)

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US7241805B2 (en) 2005-06-27 2007-07-10 Biovail Laboratories, Inc. Modified release formulations of a bupropion salt
WO2008099418A2 (en) * 2007-02-12 2008-08-21 Alembic Limited An improved process for preparing bupropion hydrochloride
CN106431943A (en) * 2016-09-13 2017-02-22 威海迪素制药有限公司 Preparing method of bupropion hydrochloride crystal
US11844797B1 (en) 2023-04-20 2023-12-19 Antecip Bioventures Ii Llc Combination of dextromethorphan and bupropion for treating depression
WO2024006904A1 (en) * 2022-06-30 2024-01-04 Axsome Therapeutics, Inc. Microparticles containing bupropion
US11883373B1 (en) 2022-07-07 2024-01-30 Antecip Bioventures Ii Llc Treatment of depression in certain patient populations
US11896563B2 (en) 2020-12-01 2024-02-13 Antecip Bioventures Ii Llc Bupropion and dextromethorphan for reduction of suicide risk in depression patients
US11925636B2 (en) 2022-06-30 2024-03-12 Antecip Bioventures Ii Llc Bupropion dosage forms with reduced food and alcohol dosing effects

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US6238697B1 (en) * 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
US6306436B1 (en) * 2000-04-28 2001-10-23 Teva Pharmaceuticals Usa, Inc. Stabilized, acid-free formulation for sustained release of bupropion hydrochloride

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US3819706A (en) * 1969-12-04 1974-06-25 Burroughs Wellcome Co Meta chloro substituted-alpha-butylamino-propiophenones
US6238697B1 (en) * 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
US6306436B1 (en) * 2000-04-28 2001-10-23 Teva Pharmaceuticals Usa, Inc. Stabilized, acid-free formulation for sustained release of bupropion hydrochloride

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7241805B2 (en) 2005-06-27 2007-07-10 Biovail Laboratories, Inc. Modified release formulations of a bupropion salt
US7884136B2 (en) 2005-06-27 2011-02-08 Biovail Laboratories International S.R.L. Modified-release formulations of a bupropion salt
US8932628B2 (en) 2005-06-27 2015-01-13 Valeant International Bermuda Modified release formulations of a bupropion salt
US9504640B2 (en) 2005-06-27 2016-11-29 Valeant Pharmaceuticals Luxembourg S.Á.R.L. Modified release formulations of a bupropion salt
WO2008099418A2 (en) * 2007-02-12 2008-08-21 Alembic Limited An improved process for preparing bupropion hydrochloride
WO2008099418A3 (en) * 2007-02-12 2008-11-13 Alembic Ltd An improved process for preparing bupropion hydrochloride
CN106431943A (en) * 2016-09-13 2017-02-22 威海迪素制药有限公司 Preparing method of bupropion hydrochloride crystal
CN106431943B (en) * 2016-09-13 2021-03-26 迪嘉药业集团有限公司 Preparation method of bupropion hydrochloride crystal
US11896563B2 (en) 2020-12-01 2024-02-13 Antecip Bioventures Ii Llc Bupropion and dextromethorphan for reduction of suicide risk in depression patients
WO2024006904A1 (en) * 2022-06-30 2024-01-04 Axsome Therapeutics, Inc. Microparticles containing bupropion
US11925636B2 (en) 2022-06-30 2024-03-12 Antecip Bioventures Ii Llc Bupropion dosage forms with reduced food and alcohol dosing effects
US11883373B1 (en) 2022-07-07 2024-01-30 Antecip Bioventures Ii Llc Treatment of depression in certain patient populations
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