WO2005019199A1 - Amorphous duloxetine hydrochloride - Google Patents
Amorphous duloxetine hydrochloride Download PDFInfo
- Publication number
- WO2005019199A1 WO2005019199A1 PCT/IN2003/000280 IN0300280W WO2005019199A1 WO 2005019199 A1 WO2005019199 A1 WO 2005019199A1 IN 0300280 W IN0300280 W IN 0300280W WO 2005019199 A1 WO2005019199 A1 WO 2005019199A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- amorphous
- solvent
- duloxetine hydrochloride
- ketone
- duloxetine
- Prior art date
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Classifications
-
- 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
Definitions
- the present invention relates to a novel amorphous form of duloxetine hydrochloride, to a process for its preparation and to a pharmaceutical composition containing it.
- the novel amorphous duloxetine hydrochloride is found to have better dissolution rate than the known crystalline duloxetine hydrochloride. So, the novel form is suitable for pharmaceutical preparations.
- the object of the present invention is to provide a novel stable amorphous form of duloxetine hydrochloride, process for preparing it and a pharmaceutical composition containing it. DETAILED DESCRIPTION OF THE INVENTION
- a novel amorphous duloxetine hydrochloride is characterized by having broad x-ray diffraction spectrum as in figure 1.
- a process is provided for preparation of amorphous duloxetine hydrochloride.
- Amorphous duloxetine hydrochloride is prepared by dissolving duloxetine hydrochloride in an alcohol, a ketone solvent or an ester solvent and removing the solvent.
- the alcohol is selected from the group consisting of methanol, ethanol, isopropyl alcohol, tert-butyl alcohol and n-butyl alcohol.
- the ketone solvent is selected from the group consisting of acetone, diethyl ketone, methylethyl ketone, methylisobutyl ketone and methylpropyl ketone.
- the ester solvent is selected from ethylacetate and methylacetate. A mixture of two or more of these solvents may also be used.
- the preferable alcohols are ethanol and methanol.
- the solvent may be removed from the solution by vacuum drying, freeze- drying, lyophilization or spray drying.
- Duloxetine hydrochloride obtained by a known process may be used in the process.
- a pharmaceutical composition comprising amorphous duloxetine hydrochloride and a pharmaceutically acceptable carrier or diluent.
- Figure 1 is a x-ray powder diffraction spectrum of amorphous duloxetine hydrochloride. x-Ray powder diffraction spectrum was measured on a Bruker axs D8 advance x-ray powder diffractometer having a copper-Kr radiation.
- Example 1 Duloxetine hydrochloride crystals (25 gm) is dissolved in ethanol (125 ml). The solution is subjected to vacuum drying at about 60°C for 10 hours to give-22.5 gm of amorphous duloxetine hydrochloride.
- Example 2 Duloxetine hydrochloride crystals (25 gm) is dissolved in methanol (100 ml). The solution is subjected to vacuum drying at about 40°C for 9 hours to give 23 gm of amorphous duloxetine hydrochloride.
- Example 3 Duloxetine hydrochloride crystals (20 gm) is dissolved in isopropyl alcohol (140 ml).
- Example 4 Example 1 is repeated by subjecting the solution to spray drying instead of vacuum drying to give amorphous duloxetine hydrochloride.
- Example 5 Example 2 is repeated by subjecting the solution to spray drying instead of vacuum drying to give amorphous duloxetine hydrochloride.
Abstract
The present invention relates to a novel amorphous form of duloxetine hydrochloride, to a process for its preparation and to a pharmaceutical composition containing it.
Description
AMORPHOUS DULOXETINE HYDROCHLORIDE
FILELD OF THE INVENTION
The present invention relates to a novel amorphous form of duloxetine hydrochloride, to a process for its preparation and to a pharmaceutical composition containing it. BACKGROUND OF THE INVENTION
Duloxetine of formula (1):
or (γS)-Λ/-Methyl-γ-(1-naphthalenyioxy)-2-thiophenepropanamine and its salts are Dual serotonin and norepinephrine reuptake inhibitors (SNRI) and its therapeutic uses were disclosed in US 5,023,269. The process for preparation of duloxetine hydrochloride was described in US 5,362,886. The processes described in the prior art produce crystalline duloxetine hydrochloride. It is well known that pharmaceutical products in amorphous form usually have better dissolution characteristics than when they are in crystalline form. We discovered a sufficiently stable amorphous form of duloxetine hydrochloride. The novel amorphous duloxetine hydrochloride is found to have better dissolution rate than the known crystalline duloxetine hydrochloride. So, the novel form is suitable for pharmaceutical preparations.
The object of the present invention is to provide a novel stable amorphous form of duloxetine hydrochloride, process for preparing it and a pharmaceutical composition containing it. DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, there is provided a novel amorphous duloxetine hydrochloride. The amorphous duloxetine hydrochloride is characterized by having broad x-ray diffraction spectrum as in figure 1. In accordance with the present invention, a process is provided for preparation of amorphous duloxetine hydrochloride. Amorphous duloxetine hydrochloride is prepared by dissolving duloxetine hydrochloride in an alcohol, a ketone solvent or an ester solvent and removing the solvent. The alcohol is selected from the group consisting of methanol, ethanol, isopropyl alcohol, tert-butyl alcohol and n-butyl alcohol. The ketone solvent is selected from the group consisting of acetone, diethyl ketone, methylethyl ketone, methylisobutyl ketone and methylpropyl ketone. The ester solvent is selected from ethylacetate and methylacetate. A mixture of two or more of these solvents may also be used. The preferable alcohols are ethanol and methanol. The solvent may be removed from the solution by vacuum drying, freeze- drying, lyophilization or spray drying. Duloxetine hydrochloride obtained by a known process may be used in the process. In accordance with the present invention, there is provided a pharmaceutical composition comprising amorphous duloxetine hydrochloride and a pharmaceutically acceptable carrier or diluent.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a x-ray powder diffraction spectrum of amorphous duloxetine hydrochloride. x-Ray powder diffraction spectrum was measured on a Bruker axs D8 advance x-ray powder diffractometer having a copper-Kr radiation.
The invention will now be further described by the following non-limiting examples.
Example 1 Duloxetine hydrochloride crystals (25 gm) is dissolved in ethanol (125 ml). The solution is subjected to vacuum drying at about 60°C for 10 hours to give-22.5 gm of amorphous duloxetine hydrochloride. Example 2 Duloxetine hydrochloride crystals (25 gm) is dissolved in methanol (100 ml). The solution is subjected to vacuum drying at about 40°C for 9 hours to give 23 gm of amorphous duloxetine hydrochloride. Example 3 Duloxetine hydrochloride crystals (20 gm) is dissolved in isopropyl alcohol (140 ml). The solution is subjected to vacuum drying at about 60°C for 8 hours to give 19 gm of amorphous duloxetine hydrochloride. Example 4 Example 1 is repeated by subjecting the solution to spray drying instead of vacuum drying to give amorphous duloxetine hydrochloride. Example 5 Example 2 is repeated by subjecting the solution to spray drying instead of vacuum drying to give amorphous duloxetine hydrochloride.
Claims
1. Amorphous duloxetine hydrochloride characterized by an x-ray powder diffraction spectrum as in figure 1.
2. A process for preparation of amorphous duloxetine hydrochloride as defined in claim 1 , which comprises the steps of: a) dissolving duloxetine hydrochjoride in a solvent; and b) removing the solvent from the solution formed in step (a) by vacuum drying, freeze drying, lyophilization or spray drying; wherein the solvent is selcted from methanol, ethanol, isopropyl alcohol, tert- butyl alcohol, n-butyl alcohol, acetone, diethyl ketone, methylethyl ketone, methylisobutyl ketone, methylpropyl ketone, ethylacetate, methylacetate and a mixture thereof.
3. A process according to claim 2, wherein the solvent is ethanol.
4. A process according to claim 2, wherein the solvent is methanol.
5. A process according to claim 2, wherein the solvent is removed by vacuum drying.
6. A process according to claim 2, wherein the solvent is removed by spray drying.
7. A pharmaceutical composition comprising amorphous duloxetine hydrochloride as defined in claim 1 and a pharmaceutically acceptable carrier or diluent.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2003/000280 WO2005019199A1 (en) | 2003-08-25 | 2003-08-25 | Amorphous duloxetine hydrochloride |
| AU2003263585A AU2003263585A1 (en) | 2003-08-25 | 2003-08-25 | Amorphous duloxetine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2003/000280 WO2005019199A1 (en) | 2003-08-25 | 2003-08-25 | Amorphous duloxetine hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2005019199A1 true WO2005019199A1 (en) | 2005-03-03 |
Family
ID=34204121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2003/000280 WO2005019199A1 (en) | 2003-08-25 | 2003-08-25 | Amorphous duloxetine hydrochloride |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003263585A1 (en) |
| WO (1) | WO2005019199A1 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006081515A2 (en) * | 2005-01-27 | 2006-08-03 | Teva Pharmaceutical Industries Ltd. | Duloxetine hydrochloride polymorphs |
| WO2007067581A1 (en) * | 2005-12-05 | 2007-06-14 | Teva Pharmaceutical Industries Ltd. | 2-(n-methyl-propanamine)-3-(2-naphthol) thiophene, an impurity of duloxetine hydrochloride |
| WO2008004190A2 (en) * | 2006-07-03 | 2008-01-10 | Ranbaxy Laboratories Limited | Polymorphic form of duloxetine hydrochloride |
| US7534900B2 (en) | 2005-03-14 | 2009-05-19 | Teva Pharmaceutical Industries Ltd | Process for the purification of duloxetine hydrochloride |
| US7795455B2 (en) | 2006-06-23 | 2010-09-14 | Chongqing Shenghuaxi Pharmaceuticals Co. Ltd. | Crystalline duloxetine hydrochloride |
| US7799935B2 (en) | 2006-06-23 | 2010-09-21 | Chongqing Shenghuaxi Pharmaceuticals Co. Ltd. | Crystalline duloxetine hydrochloride |
| EP2308864A1 (en) | 2006-02-17 | 2011-04-13 | KRKA, tovarna zdravil, d.d., Novo mesto | Pharmaceutical formulation of duloxetine hydrochloride |
| WO2011128370A1 (en) | 2010-04-13 | 2011-10-20 | Krka, D.D., Novo Mesto | Synthesis of duloxetine and/or pharmaceutically acceptable salts thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0650965A1 (en) * | 1993-10-12 | 1995-05-03 | Eli Lilly And Company | Asymmetric synthesis of (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine an intermediate in the preparation of duloxetine |
| WO2003062219A1 (en) * | 2002-01-24 | 2003-07-31 | Eli Lilly And Company | Process for preparing an intermediate useful for the asymmetric synthesis of duloxetine |
-
2003
- 2003-08-25 AU AU2003263585A patent/AU2003263585A1/en not_active Abandoned
- 2003-08-25 WO PCT/IN2003/000280 patent/WO2005019199A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0650965A1 (en) * | 1993-10-12 | 1995-05-03 | Eli Lilly And Company | Asymmetric synthesis of (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine an intermediate in the preparation of duloxetine |
| WO2003062219A1 (en) * | 2002-01-24 | 2003-07-31 | Eli Lilly And Company | Process for preparing an intermediate useful for the asymmetric synthesis of duloxetine |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006081515A2 (en) * | 2005-01-27 | 2006-08-03 | Teva Pharmaceutical Industries Ltd. | Duloxetine hydrochloride polymorphs |
| WO2006081515A3 (en) * | 2005-01-27 | 2007-11-01 | Teva Pharma | Duloxetine hydrochloride polymorphs |
| US7534900B2 (en) | 2005-03-14 | 2009-05-19 | Teva Pharmaceutical Industries Ltd | Process for the purification of duloxetine hydrochloride |
| EP2100888A3 (en) * | 2005-12-05 | 2011-01-19 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of duloxetine hydrochloride |
| US7759500B2 (en) | 2005-12-05 | 2010-07-20 | Teva Pharmaceutical Industries Ltd. | 2-(N-methyl-propanamine)-3-(2-naphthol)thiophene, an impurity of duloxetine hydrochloride |
| WO2007067581A1 (en) * | 2005-12-05 | 2007-06-14 | Teva Pharmaceutical Industries Ltd. | 2-(n-methyl-propanamine)-3-(2-naphthol) thiophene, an impurity of duloxetine hydrochloride |
| EP2308864A1 (en) | 2006-02-17 | 2011-04-13 | KRKA, tovarna zdravil, d.d., Novo mesto | Pharmaceutical formulation of duloxetine hydrochloride |
| US7795455B2 (en) | 2006-06-23 | 2010-09-14 | Chongqing Shenghuaxi Pharmaceuticals Co. Ltd. | Crystalline duloxetine hydrochloride |
| US7799935B2 (en) | 2006-06-23 | 2010-09-21 | Chongqing Shenghuaxi Pharmaceuticals Co. Ltd. | Crystalline duloxetine hydrochloride |
| US8093407B2 (en) | 2006-06-23 | 2012-01-10 | Arrow International Limited | Crystalline duloxetine hydrochloride |
| WO2008004190A3 (en) * | 2006-07-03 | 2008-04-03 | Ranbaxy Lab Ltd | Polymorphic form of duloxetine hydrochloride |
| WO2008004190A2 (en) * | 2006-07-03 | 2008-01-10 | Ranbaxy Laboratories Limited | Polymorphic form of duloxetine hydrochloride |
| WO2011128370A1 (en) | 2010-04-13 | 2011-10-20 | Krka, D.D., Novo Mesto | Synthesis of duloxetine and/or pharmaceutically acceptable salts thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003263585A1 (en) | 2005-03-10 |
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