EP2197446A2 - Preparation of ziprasidone hydrochloride monohydrate - Google Patents

Preparation of ziprasidone hydrochloride monohydrate

Info

Publication number
EP2197446A2
EP2197446A2 EP08829913A EP08829913A EP2197446A2 EP 2197446 A2 EP2197446 A2 EP 2197446A2 EP 08829913 A EP08829913 A EP 08829913A EP 08829913 A EP08829913 A EP 08829913A EP 2197446 A2 EP2197446 A2 EP 2197446A2
Authority
EP
European Patent Office
Prior art keywords
ziprasidone hydrochloride
process according
hydrochloride monohydrate
mean particle
particle sizes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08829913A
Other languages
German (de)
French (fr)
Other versions
EP2197446A4 (en
Inventor
Brahmeswara Rao Venkata Naga Mandava
Surya Narayana Devarakonda
Subba Reddy Peddireddy
Radha Krishna Singamsetty
Naga Raju Manne
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dr Reddys Laboratories Ltd
Dr Reddys Laboratories Inc
Original Assignee
Dr Reddys Laboratories Ltd
Dr Reddys Laboratories Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dr Reddys Laboratories Ltd, Dr Reddys Laboratories Inc filed Critical Dr Reddys Laboratories Ltd
Publication of EP2197446A2 publication Critical patent/EP2197446A2/en
Publication of EP2197446A4 publication Critical patent/EP2197446A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present application relates to processes for the preparation of ziprasidone or salts thereof with defined particle size distribution parameters.
  • Ziprasidone hydrochloride is the adopted name for a drug having a chemical name 5-[2-[4-(1 ,2-benzoisothiazol-3-yl)-1 -piperazinyl]ethyl]-6-chloro-1 ,3- dihydro-2H-indol-2-one hydrochloride monohydrate, and having structural Formula I.
  • ziprasidone, ziprasidone hydrochloride and other pharmaceutically acceptable salts are useful as antipsychotic agents in the treatment of schizophrenia
  • ziprasidone hydrochloride monohydrate is commercially available as the active ingredient in GEODONTM Capsules, sold by the Roerig division of Pfizer Inc. in 20 mg, 40 mg, 60 mg and 80 mg dosage strengths.
  • U.S. Patent No. 5,312,925 discloses process to prepare ziprasidone hydrochloride monohydrate by heating a mixture of hydrochloric acid, water and anhydrous ziprasidone free base.
  • U.S. Patent No. 6,150,366 discloses a process for the preparation of ziprasidone hydrochloride monohydrate which involves adding dilute hydrochloric acid to a solution of ziprasidone free base, in a mixture of tetrahydrofuran and water, followed by heating the mixture.
  • process for preparation of ziprasidone hydrochloride monohydrate from anhydrous ziprasidone hydrochloride while retaining the mean particle size greater than about 90 ⁇ m, or about 90 ⁇ m to about 300 ⁇ m.
  • step (b) isolating particles of ziprasidone hydrochloride monohydrate.
  • the solid isolated in step (b) is dry milled to achieve the desired particle sizes.
  • step (3) isolating particles of ziprasidone hydrochloride monohydrate.
  • the solid isolated in step (3) is dry milled to achieve the desired particle sizes.
  • compositions comprising ziprasidone hydrochloride monohydrate and at least one pharmaceutically acceptable carrier, wherein ziprasidone hydrochloride monohydrate has mean particle sizes greater than about 90 ⁇ m, or about 90 ⁇ m to about 300 ⁇ m.
  • the term "particles" refers to individual particles regardless of whether the particles exist singly or are agglomerated with each other.
  • the mean particle size is defined as the average of the maximum dimensions of all particles present in a given sample. The sizes of all particles present in any sample can be characterized by a particle size distribution. The mean particle size is frequently expressed in ⁇ m, and can measured using a particle size analyzer, such as using laser light scattering equipment from Malvern Instruments Ltd., Malvern, Worcestershire, United Kingdom. Other types of particle size measuring equipment are also suitable, as will be appreciated by those skilled in the art.
  • An embodiment of a process includes: (a) mixing anhydrous ziprasidone hydrochloride with a mixture of water and a water miscible solvent; and
  • step (b) isolating particles of ziprasidone hydrochloride monohydrate.
  • the solid isolated in step (b) is dry milled to achieve the desired particle sizes.
  • suitable water miscible solvents include: alcohols, such as methanol, ethanol, n-propanol, isopropyl alcohol, and n- butanol; ketones, such as acetone and methyl ethyl ketone; nithles, such as acetonithle and propionitrile; aprotic solvents, such as N,N-dimethylformamide (DMF), and dimethylsulfoxide (DMSO); and mixtures thereof.
  • DMF N,N-dimethylformamide
  • DMSO dimethylsulfoxide
  • the relative amounts of water miscible solvent and water in the solvent mixtures are not particularly restricted, in certain embodiments the percentages of water in the mixtures are in the range of from about 10% to about 90%, or about 10% to about 70%, or about 10% to about 50%, expressed on a volume basis. Suitable temperatures for mixing the solid with the liquid range from about
  • step (a) is typically mixed for about 20 minutes to about 5 hours.
  • suitable agitators for mixing the slurry include anchor, propeller, TeflonTM blade and other types of stirrers.
  • the rotational speed of an agitator may be about 100-500 rpm, or any other desired speed.
  • the isolation of solid includes separating a solid from the slurry.
  • the separation methods may include, for example, decantation, filtration by gravity or by suction, or centrifugation.
  • the solid so isolated may carry some occluded mother liquor. If desired, the separated solid may be washed with a solvent or mixture of solvents in various proportions to remove the occluded mother liquor.
  • the isolated solid may be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like. The drying may be carried out at temperatures of from about 25°C to about 55°C, with or without the application of vacuum. The drying may be carried out for sufficient time to achieve the product with desired specifications, including moisture contents. The time periods may vary from about 30 minutes to about 20 hours, or longer.
  • the dried solid typically has mean particle sizes from about 90 ⁇ m to about 300 ⁇ m, or from about 100 ⁇ m to about 200 ⁇ m, or from about 100 ⁇ m to about 150 ⁇ m.
  • the solid After drying, the solid may be milled to modify the particle size. Milling may be carried out using equipment having 0.1 mm to 5 mm mesh screens to provide ziprasidone hydrochloride monohydrate with defined particle size distribution parameters.
  • An embodiment of a process includes: (1 ) preparing a stationary bed of anhydrous ziprasidone hydrochloride,
  • the solid isolated in step (3) is dry milled to achieve the desired particle sizes.
  • a stationary bed of anhydrous ziprasidone hydrochloride is prepared on filter media.
  • suitable filter media on which a stationary bed may be prepared include a B ⁇ chner funnel, Nutsche filter, sintered glass filter or other similar filter.
  • a piece of filter paper may be placed in a B ⁇ chner funnel to cover the openings and avoid creeping of the small particles of the bed material into the liquid.
  • anhydrous ziprasidone hydrochloride is loaded onto the top of the filter to serve as a filter bed.
  • the filtration operation may be carried out under reduced pressure to speed up the process.
  • step (2) a mixture of water and a water miscible solvent is passed through the bed.
  • Non-limiting examples of suitable water miscible solvents include: CrC 4 alcohols, such as methanol, ethanol, n-propanol, isopropyl alcohol, and n-butanol; ketones, such as acetone and methyl ethyl ketone; nitriles, such as acetonithle and propionitrile; aprotic solvents, such as N,N-dimethylformamide (DMF) and dimethylsulfoxide (DMSO); and mixtures thereof.
  • CrC 4 alcohols such as methanol, ethanol, n-propanol, isopropyl alcohol, and n-butanol
  • ketones such as acetone and methyl ethyl ketone
  • nitriles such as acetonithle and propionitrile
  • aprotic solvents such as N,N-dimethylformamide (DMF) and dimethylsulfoxide (DMSO); and mixtures thereof.
  • the relative amounts of water miscible solvent and water in the solvent mixtures are not particularly restricted, in certain embodiments the percentages of water in the mixtures are in the range of from about 10% to about 90%, or about 10% to about 70%, or about 10% to about 50%, expressed on a volume basis.
  • Suitable temperatures for passing the solvent through the filter bed range from about 15°C to about 45°C.
  • the solid cake may be removed from the filter and dried. Drying may be carried out under reduced pressure. Drying may be carried out in equipment such as a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like. The drying may be carried out at temperatures of from about 25°C to about 55°C, with or without vacuum. The drying may be carried out for a sufficient time period to achieve the desired product specifications, including moisture contents.
  • the dried solid has mean particle sizes from about 90 ⁇ m to about 300 ⁇ m, or from about 100 ⁇ m to about 200 ⁇ m, or from about 100 ⁇ m to about 150 ⁇ m.
  • the solid After drying, the solid may be milled to modify the particle size. Milling may be carried out using equipment having 0.1 mm to 5 mm mesh screens to provide ziprasidone hydrochloride monohydrate with defined particle sizes.
  • compositions comprising ziprasidone hydrochloride monohydrate and at least one pharmaceutically acceptable excipient, wherein ziprasidone hydrochloride monohydrate has mean particle sizes greater than about 90 ⁇ m, or about 90 ⁇ m to about 300 ⁇ m, or about 100 ⁇ m to about 200 ⁇ m, or about 100 ⁇ m to about 150 ⁇ m.
  • ziprasidone hydrochloride monohydrate in the formulations contains less than about 0.25% of any individual impurity.
  • the composition may be formulated into solid pharmaceutical dosage forms such as tablets, powders for oral suspension, unit dose packets, and capsules for oral administration, and such dosage forms can be made using conventional methodology.
  • compositions in addition to ziprasidone free base or ziprasidone hydrochloride, may contain conventional pharmaceutically acceptable excipients such as, for example: fillers and diluents such as starches and sugars; binders such as carboxymethylcellulose and other cellulose derivatives, alginates, gelatine, and polyvinylpyrrolidine; disintegrating agents such as agar-agar, calcium carbonate and sodium bicarbonate, pregelatinized starch, sodium croscarmellose, sodium starch glycolate and crosslinked poly(vinylpyrrolidine); lubricants such as talc, sodium lauryl sulfate, stearic acid, calcium and magnesium stearate, and polyethylene glycols.
  • fillers and diluents such as starches and sugars
  • binders such as carboxymethylcellulose and other cellulose derivatives, alginates, gelatine, and polyvinylpyrrolidine
  • disintegrating agents such as agar-agar, calcium carbonate and sodium bicarbon
  • excipients can also serve more than one function; for example, a disintegrant can also serve as a filler.
  • anhydrous ziprasidone hydrochloride (20 Kg) having a mean particle size about 143 ⁇ m was charged at about 30 0 C and the resulting slurry was stirred for 30 minutes.
  • the solid was separated with a centrifuge, washed with a mixture of methanol (16 L) and water (4 L) and spin-dried for 3 hours. The solid was further dried at about 30 0 C under reduced pressure to obtain ziprasidone hydrochloride monohydrate having a mean particle size about 138 ⁇ m (yield: 20 Kg).
  • EXAMPLE 2 A stationary bed of anhydrous ziprasidone hydrochloride (100 g) having a mean particle size about 143 ⁇ m was prepared on a B ⁇ chner funnel. A mixture of methanol (450 ml) and water (50 ml) was slowly poured onto this bed for a period of 30 minutes. The traces of solvent were removed from the bed by applying vacuum/nitrogen for about 45 minutes. The solid was further dried at 50-55 0 C in a hot air oven for 30 minutes to obtain ziprasidone hydrochloride monohydrate having a mean particle size about 140 ⁇ m (yield: 104 g).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Methods for the preparation of ziprasidone hydrochloride monohydrate having definite particle size distribution parameters, from anhydrous ziprasidone hydrochloride.

Description

PREPARATION OF ZIPRASIDONE HYDROCHLORIDE MONOHYDRATE
INTRODUCTION
The present application relates to processes for the preparation of ziprasidone or salts thereof with defined particle size distribution parameters.
Ziprasidone hydrochloride is the adopted name for a drug having a chemical name 5-[2-[4-(1 ,2-benzoisothiazol-3-yl)-1 -piperazinyl]ethyl]-6-chloro-1 ,3- dihydro-2H-indol-2-one hydrochloride monohydrate, and having structural Formula I.
Formula I
Ziprasidone, ziprasidone hydrochloride and other pharmaceutically acceptable salts are useful as antipsychotic agents in the treatment of schizophrenia, ziprasidone hydrochloride monohydrate is commercially available as the active ingredient in GEODON™ Capsules, sold by the Roerig division of Pfizer Inc. in 20 mg, 40 mg, 60 mg and 80 mg dosage strengths.
U.S. Patent No. 5,312,925 discloses process to prepare ziprasidone hydrochloride monohydrate by heating a mixture of hydrochloric acid, water and anhydrous ziprasidone free base. U.S. Patent No. 6,150,366 discloses a process for the preparation of ziprasidone hydrochloride monohydrate which involves adding dilute hydrochloric acid to a solution of ziprasidone free base, in a mixture of tetrahydrofuran and water, followed by heating the mixture.
SUMMARY
There are provided herein processes for the preparation of ziprasidone hydrochloride monohydrate having mean particle sizes greater than about 90 μm.
In an embodiment, there are provided process for preparation of ziprasidone hydrochloride monohydrate from anhydrous ziprasidone hydrochloride, while retaining the mean particle size greater than about 90 μm, or about 90 μm to about 300 μm.
In an aspect, there are provided processes for preparation of ziprasidone hydrochloride monohydrate with mean particle sizes greater than about 90 μm, from anhydrous ziprasidone hydrochloride with mean particle sizes greater than about 90 μm, an embodiment comprising:
(a) mixing anhydrous ziprasidone hydrochloride with a mixture of water and a water miscible solvent; and
(b) isolating particles of ziprasidone hydrochloride monohydrate. In embodiments, the solid isolated in step (b) is dry milled to achieve the desired particle sizes.
In another aspect, there are provided processes for preparation of ziprasidone hydrochloride monohydrate having mean particle sizes greater than about 90 μm, from anhydrous ziprasidone hydrochloride having mean particle sizes greater than about 90 μm, an embodiment comprising:
(1 ) preparing a stationary bed of anhydrous ziprasidone hydrochloride,
(2) passing a mixture of water and a water miscible solvent through the bed; and
(3) isolating particles of ziprasidone hydrochloride monohydrate. In embodiments, the solid isolated in step (3) is dry milled to achieve the desired particle sizes.
In embodiments, there are provided pharmaceutical compositions comprising ziprasidone hydrochloride monohydrate and at least one pharmaceutically acceptable carrier, wherein ziprasidone hydrochloride monohydrate has mean particle sizes greater than about 90 μm, or about 90 μm to about 300 μm.
DETAILED DESCRIPTION
As used herein with regard to ziprasidone and its salts, the term "particles" refers to individual particles regardless of whether the particles exist singly or are agglomerated with each other. The mean particle size is defined as the average of the maximum dimensions of all particles present in a given sample. The sizes of all particles present in any sample can be characterized by a particle size distribution. The mean particle size is frequently expressed in μm, and can measured using a particle size analyzer, such as using laser light scattering equipment from Malvern Instruments Ltd., Malvern, Worcestershire, United Kingdom. Other types of particle size measuring equipment are also suitable, as will be appreciated by those skilled in the art.
There are provided processes for preparation of ziprasidone hydrochloride monohydrate having mean particle sizes greater than about 90 μm, from anhydrous ziprasidone hydrochloride having mean particle sizes greater than about 90 μm. An embodiment of a process includes: (a) mixing anhydrous ziprasidone hydrochloride with a mixture of water and a water miscible solvent; and
(b) isolating particles of ziprasidone hydrochloride monohydrate. In embodiments, the solid isolated in step (b) is dry milled to achieve the desired particle sizes. Non-limiting examples of suitable water miscible solvents include: alcohols, such as methanol, ethanol, n-propanol, isopropyl alcohol, and n- butanol; ketones, such as acetone and methyl ethyl ketone; nithles, such as acetonithle and propionitrile; aprotic solvents, such as N,N-dimethylformamide (DMF), and dimethylsulfoxide (DMSO); and mixtures thereof. While the relative amounts of water miscible solvent and water in the solvent mixtures are not particularly restricted, in certain embodiments the percentages of water in the mixtures are in the range of from about 10% to about 90%, or about 10% to about 70%, or about 10% to about 50%, expressed on a volume basis. Suitable temperatures for mixing the solid with the liquid range from about
00C to about 600C, or about 25°C to about 35°C. The slurry of step (a) is typically mixed for about 20 minutes to about 5 hours. Examples of suitable agitators for mixing the slurry include anchor, propeller, Teflon™ blade and other types of stirrers. The rotational speed of an agitator may be about 100-500 rpm, or any other desired speed.
The isolation of solid includes separating a solid from the slurry. The separation methods may include, for example, decantation, filtration by gravity or by suction, or centrifugation. The solid so isolated may carry some occluded mother liquor. If desired, the separated solid may be washed with a solvent or mixture of solvents in various proportions to remove the occluded mother liquor.
The isolated solid may be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like. The drying may be carried out at temperatures of from about 25°C to about 55°C, with or without the application of vacuum. The drying may be carried out for sufficient time to achieve the product with desired specifications, including moisture contents. The time periods may vary from about 30 minutes to about 20 hours, or longer. The dried solid typically has mean particle sizes from about 90 μm to about 300 μm, or from about 100 μm to about 200 μm, or from about 100 μm to about 150 μm.
After drying, the solid may be milled to modify the particle size. Milling may be carried out using equipment having 0.1 mm to 5 mm mesh screens to provide ziprasidone hydrochloride monohydrate with defined particle size distribution parameters.
Also provided are alternate processes for preparation of ziprasidone hydrochloride monohydrate having mean particle sizes greater than about 90 μm, from anhydrous ziprasidone hydrochloride having mean particle sizes greater than about 90 μm. An embodiment of a process includes: (1 ) preparing a stationary bed of anhydrous ziprasidone hydrochloride,
(2) passing a mixture of water and a water miscible solvent through the bed; and
(3) isolating particles of ziprasidone hydrochloride monohydrate.
In embodiments, the solid isolated in step (3) is dry milled to achieve the desired particle sizes.
In step (1 ), a stationary bed of anhydrous ziprasidone hydrochloride is prepared on filter media. Examples of suitable filter media on which a stationary bed may be prepared include a Bϋchner funnel, Nutsche filter, sintered glass filter or other similar filter. A piece of filter paper may be placed in a Bϋchner funnel to cover the openings and avoid creeping of the small particles of the bed material into the liquid. Typically, anhydrous ziprasidone hydrochloride is loaded onto the top of the filter to serve as a filter bed. Optionally, the filtration operation may be carried out under reduced pressure to speed up the process. In step (2), a mixture of water and a water miscible solvent is passed through the bed. Non-limiting examples of suitable water miscible solvents include: CrC4 alcohols, such as methanol, ethanol, n-propanol, isopropyl alcohol, and n-butanol; ketones, such as acetone and methyl ethyl ketone; nitriles, such as acetonithle and propionitrile; aprotic solvents, such as N,N-dimethylformamide (DMF) and dimethylsulfoxide (DMSO); and mixtures thereof.
While the relative amounts of water miscible solvent and water in the solvent mixtures are not particularly restricted, in certain embodiments the percentages of water in the mixtures are in the range of from about 10% to about 90%, or about 10% to about 70%, or about 10% to about 50%, expressed on a volume basis.
Suitable temperatures for passing the solvent through the filter bed range from about 15°C to about 45°C.
The solid cake may be removed from the filter and dried. Drying may be carried out under reduced pressure. Drying may be carried out in equipment such as a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like. The drying may be carried out at temperatures of from about 25°C to about 55°C, with or without vacuum. The drying may be carried out for a sufficient time period to achieve the desired product specifications, including moisture contents. The dried solid has mean particle sizes from about 90 μm to about 300 μm, or from about 100 μm to about 200 μm, or from about 100 μm to about 150 μm.
After drying, the solid may be milled to modify the particle size. Milling may be carried out using equipment having 0.1 mm to 5 mm mesh screens to provide ziprasidone hydrochloride monohydrate with defined particle sizes.
Also provided are pharmaceutical compositions comprising ziprasidone hydrochloride monohydrate and at least one pharmaceutically acceptable excipient, wherein ziprasidone hydrochloride monohydrate has mean particle sizes greater than about 90 μm, or about 90 μm to about 300 μm, or about 100 μm to about 200 μm, or about 100 μm to about 150 μm. In embodiments, ziprasidone hydrochloride monohydrate in the formulations contains less than about 0.25% of any individual impurity. The composition may be formulated into solid pharmaceutical dosage forms such as tablets, powders for oral suspension, unit dose packets, and capsules for oral administration, and such dosage forms can be made using conventional methodology. The compositions, in addition to ziprasidone free base or ziprasidone hydrochloride, may contain conventional pharmaceutically acceptable excipients such as, for example: fillers and diluents such as starches and sugars; binders such as carboxymethylcellulose and other cellulose derivatives, alginates, gelatine, and polyvinylpyrrolidine; disintegrating agents such as agar-agar, calcium carbonate and sodium bicarbonate, pregelatinized starch, sodium croscarmellose, sodium starch glycolate and crosslinked poly(vinylpyrrolidine); lubricants such as talc, sodium lauryl sulfate, stearic acid, calcium and magnesium stearate, and polyethylene glycols. Some excipients can also serve more than one function; for example, a disintegrant can also serve as a filler. Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided by way of illustration only and should not be construed as limiting the scope of the invention in any manner.
EXAMPLE 1
To a solution of methanol (80 L) and water (20 L) in a reactor, anhydrous ziprasidone hydrochloride (20 Kg) having a mean particle size about 143 μm was charged at about 300C and the resulting slurry was stirred for 30 minutes. The solid was separated with a centrifuge, washed with a mixture of methanol (16 L) and water (4 L) and spin-dried for 3 hours. The solid was further dried at about 300C under reduced pressure to obtain ziprasidone hydrochloride monohydrate having a mean particle size about 138 μm (yield: 20 Kg).
EXAMPLE 2 A stationary bed of anhydrous ziprasidone hydrochloride (100 g) having a mean particle size about 143 μm was prepared on a Bϋchner funnel. A mixture of methanol (450 ml) and water (50 ml) was slowly poured onto this bed for a period of 30 minutes. The traces of solvent were removed from the bed by applying vacuum/nitrogen for about 45 minutes. The solid was further dried at 50-550C in a hot air oven for 30 minutes to obtain ziprasidone hydrochloride monohydrate having a mean particle size about 140 μm (yield: 104 g).

Claims

CLAIMS:
1. A process for the preparation of ziprasidone hydrochloride monohydrate particles, comprising:
(a) forming a slurry of anhydrous ziprasidone hydrochloride having mean particle sizes greater than about 90 μm with a mixture of water and a water miscible solvent; and
(b) isolating ziprasidone hydrochloride monohydrate particles having mean particle sizes greater than about 90 μm.
2. A process for the preparation of ziprasidone hydrochloride monohydrate particles, comprising:
(i) preparing a stationary bed of anhydrous ziprasidone hydrochloride particles having mean particle sizes greater than about 90 μm,
(ii) passing a mixture of water and a water miscible solvent through the bed; and
(iii) isolating ziprasidone hydrochloride monohydrate particles having mean particle sizes greater than about 90 μm.
3. The process according to claims 1 or 2, wherein a water miscible solvent comprises an alcohol, a ketone, a nitrile, N,N-dimethylformamide, dimethylsulfoxide, or a mixture of any two or more thereof.
4. The process according to claims 1 or 2, wherein a water miscible solvent comprises a CrC4 alcohol.
5. The process according to claims 1 or 2, wherein a water miscible solvent comprises methanol.
6. The process according to claims 1 or 2, wherein a water miscible solvent comprises a ketone.
7. The process according to claims 1 or 2, wherein a water miscible solvent comprises a nitrile.
8. The process according to any of claims 1 -7, wherein water is present in mixtures at concentrations about 10% to about 90%, by volume.
9. The process according to claim 1 , wherein the slurry in (a) is maintained at temperatures from about 00C to about 600C.
10. The process according to claim 1 , wherein the slurry in (a) is maintained at temperatures from about 25°C to about 35°C.
11. The process according to any of claims 1 -10, further comprising drying the isolated particles.
12. The process according to any of claims 1 -11 , further comprising milling the isolated particles.
13. The process according to any of claims 1 -12, wherein mean particle sizes of ziprasidone hydrochloride monohydrate and anhydrous ziprasidone hydrochloride range from about 90 μm to about 300 μm.
14. The process according to any of claims 1 -12, wherein mean particle sizes of ziprasidone hydrochloride monohydrate and anhydrous ziprasidone hydrochloride range from about 100 μm to about 200 μm.
15. The process according to any of claims 1 -12, wherein mean particle sizes of ziprasidone hydrochloride monohydrate and anhydrous ziprasidone hydrochloride range from about 100 μm to about 150 μm.
EP08829913A 2007-08-31 2008-08-22 Preparation of ziprasidone hydrochloride monohydrate Withdrawn EP2197446A4 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN1955CH2007 2007-08-31
US5898408P 2008-06-05 2008-06-05
PCT/US2008/073981 WO2009032558A2 (en) 2007-08-31 2008-08-22 Preparation of ziprasidone hydrochloride monohydrate

Publications (2)

Publication Number Publication Date
EP2197446A2 true EP2197446A2 (en) 2010-06-23
EP2197446A4 EP2197446A4 (en) 2012-01-25

Family

ID=40429636

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08829913A Withdrawn EP2197446A4 (en) 2007-08-31 2008-08-22 Preparation of ziprasidone hydrochloride monohydrate

Country Status (2)

Country Link
EP (1) EP2197446A4 (en)
WO (1) WO2009032558A2 (en)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5312925A (en) * 1992-09-01 1994-05-17 Pfizer Inc. Monohydrate of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one-hydrochloride
US6150366A (en) * 1998-06-15 2000-11-21 Pfizer Inc. Ziprasidone formulations
YU34501A (en) * 2000-05-26 2003-10-31 Pfizer Products Inc. Reactive crystallization method to improve particle size
WO2004089948A1 (en) * 2003-04-11 2004-10-21 Hetero Drugs Limited Novel crystalline forms of ziprasidone hydrochloride
EP1753400A4 (en) * 2004-06-11 2012-11-28 Reddys Lab Ltd Dr Ziprasidone dosage form

Also Published As

Publication number Publication date
WO2009032558A2 (en) 2009-03-12
EP2197446A4 (en) 2012-01-25
WO2009032558A3 (en) 2009-04-23

Similar Documents

Publication Publication Date Title
KR101251726B1 (en) NILOTINIB HCl CRYSTALLINE FORMS
US20080014280A1 (en) Amorphous pregabalin and process for the preparation thereof
US9708300B2 (en) Amorphous form of vilazodone hydrochloride and process for its preparation
WO2011095059A1 (en) Polymorphs of dasatinib, preparation methods and pharmaceutical compositions thereof
WO2009084023A2 (en) Amorphous ramelteon and process for the preparation thereof
WO2010083752A1 (en) High-purity febuxostat and the method for preparation
CA2706536A1 (en) Amorphous form of heterocyclic compound, solid dispersion and pharmaceutical preparation each comprising the same, and process for production of the same
US20150018386A1 (en) Amorphous form of apixaban, process of preparation and compositions thereof
WO2013034040A1 (en) Celecoxib solid dispersion and preparation method therefor
WO2010139980A1 (en) Process for preparing crystalline dasatinib monohydrate
US20150283249A1 (en) Amorphous form of apremilast
WO2017037596A1 (en) Amorphous solid dispersion of lcz-696
US20170105937A1 (en) Olaparib co-precipitate and preparation method thereof
WO2010129636A2 (en) Lenalidomide polymorph
EP3463352A1 (en) Polymorphs of betrixaban & its maleate salt
WO2017118915A1 (en) Amorphous and crystalline solid forms of lumacaftor or its complex and preparative processes thereof
US20150307540A1 (en) Amorphous form of dapagliflozin 1,2-propanediol
WO2009032558A2 (en) Preparation of ziprasidone hydrochloride monohydrate
US20060111417A1 (en) Amorphous telmisartan
US20080014263A1 (en) Amorphous eprosartan mesylate and process for the preparation thereof
CN100488970C (en) Crystal form of adefovir dipivoxil
CN109963565B (en) Pharmaceutical composition and preparation method thereof
WO2017190715A1 (en) An amorphous form of sofosbuvir, a method of its preparation and its stabilization
WO2016203436A1 (en) Amorphous and amorphous solid dispersion of lesinurad and their preparation
US12275722B2 (en) Process of reworking a crystalline form of a glycine transport inhibitor

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100203

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

A4 Supplementary search report drawn up and despatched

Effective date: 20111222

RIC1 Information provided on ipc code assigned before grant

Ipc: C07D 417/12 20060101AFI20111216BHEP

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20120721