WO2004083230A1 - Novel crystalline forms of finasteride - Google Patents
Novel crystalline forms of finasteride Download PDFInfo
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- WO2004083230A1 WO2004083230A1 PCT/IN2003/000060 IN0300060W WO2004083230A1 WO 2004083230 A1 WO2004083230 A1 WO 2004083230A1 IN 0300060 W IN0300060 W IN 0300060W WO 2004083230 A1 WO2004083230 A1 WO 2004083230A1
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- Prior art keywords
- finasteride
- hours
- ray powder
- powder diffraction
- diffraction pattern
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
Definitions
- the present invention relates to novel crystalline forms of finasteride, to processes for their preparation and pharmaceutical compositions containing them.
- novel forms of finasteride are, thus, suitable for pharmaceutical preparations.
- object of the present invention is to provide stable novel crystalline forms of finasteride, processes for preparation of the novel crystalline forms and pharmaceutical compositions containing these novel crystalline forms.
- Form H1 a novel crystalline form of finasteride, designated as Form H1 , characterized by an x-ray powder diffraction pattern having peaks expressed as 2 ⁇ at about 5.3, 5.8, 6.8, 7.3, 9.0, 9.4, 10.7, 13.9, 14.9, 15.9, 17.3, 18.2, 19.0, 20.1 degrees.
- Figure 1 shows typical Form H1 x-ray powder diffraction pattern.
- a process for preparation of the Form H1 of finasteride comprising the steps of: a) mixing finasteride and an alcohol; b) maintaining at about 4,0°C to 60°C for about 10 minutes to 1 hour; c) cooling slowly to about 0°C to 5°C; d) maintaining for about 1 hour to 3 hours at about 0°C to 5°C; e) filtering the solid separated.
- the alcohol is methanol, ethanol or isopropyl alcohol; or mixture thereof.
- a novel crystalline form of finasteride designated as Form H2 characterized by an x-ray powder diffraction pattern having peaks expressed as 2 ⁇ at about 5.4, 9.9, 12.1 , 14.5, 15.2, 16.2, 19.3, 29.0 degrees.
- Figure 2 shows typical Form H2 x-ray powder diffraction pattern.
- a process for preparation of the Form H2 of finasteride comprising the steps of. a) dissolving finasteride in dioxane; b) maintaining at about 70°C to 80°C for about 10 minutes to 30 minutes; c) cooling the solution slowly to about 20°C to 25°C; d) maintaining at about 20°C to 25°C for about 2 hours to 4 hours; e) filtering the solid separated.
- the previously known forms or finasteride prepared by a known method may be used in the above processes.
- a pharmaceutical composition comprising Form H1 or Form H2 of finasteride.
- Figure 1 is a x-ray powder diffraction pattern of Form H1 finasteride.
- Figure 2 is a x-ray powder diffraction pattern of Form H2 finasteride. x-Ray powder diffraction spectrum was measured on a Siemens diffractometer.
- Form H1 a novel crystalline form of finasteride, designated as Form H1, characterized by an x-ray powder diffraction pattern having peaks expressed as 2 ⁇ at about 5.3, 5.8,
- Figure 1 shows typical Form H1 x-ray powder diffraction pattern.
- finasteride is mixed with an alcohol.
- the suitable alcohol is methanol or ethanol or iso propyl alcohol; or mixture thereof.
- the previously known forms or finasteride prepared by a known method may be used. The contents are maintained at about 40°C to
- Form H2 a novel crystalline form of finasteride, designated as Form H2, characterized by an x-ray powder diffraction pattern having peaks expressed as 2 ⁇ at about 5.4, 9.9,
- Figure 2 shows typical Form H2 x-ray powder diffraction pattern.
- a process for preparation of the Form H2 of finasteride is provided.
- finasteride is dissolved in dioxane, the solution is heated to about 70°C to 80°C and maintained at this temperature for about 10 minutes to 30 minutes.
- the solution is cooled slowly, in about 3 hours, to about 20°C to 25°C and maintained at the same temperature for about 2 hours to 4 hours.
- the separated crystals are filtered to give Form H2 of finasteride.
- the previously known forms or finasteride prepared by a known method may be used in the process.
- a pharmaceutical composition comprising Form H1 or Form H2 of finasteride.
- the forms of finasteride may be formulated in a form suitable for oral administration or injection.
- Example 1 Finasteride (10 gm) (obtained by a known method) is dissolved in methanol (25 ml), heated to 55°C and maintained at this temperature for 15 minutes. The solution is slowly cooled to 0°C in 3 hours and maintained at 0°C for 1.5 hours. The separated crystals are filtered at 0°C to give 8.5 gm of Form H1 of finasteride.
- Example 2 Finasteride (10 gm) (obtained by a known method) is dissolved in isopropyl alcohol (40 ml), heated to 55°C and maintained at this temperature for 15 minutes. The solution is slowly cooled to 0°C in 3 hours and maintained at 0°C for 1.5 hours. The separated crystals are filtered at 0°C to give 8.5 gm of Form H1 of finasteride.
- Example 3 Finasteride (10 gm) (obtained by a known method) is dissolved in isopropyl alcohol (40 ml), heated to 55°C and maintained at this temperature for 15 minutes. The solution is slowly cooled to 0°C in 3 hours and maintained at 0°C for 1.5 hours. The separated crystals are filtered at 0°C to give 8.5 gm of Form H1 of finasteride.
- Example 3 Finasteride (10 gm) (obtained by a known method) is dissolved in isopropyl alcohol (40 ml), heated to 55
- Finasteride (10 gm) (obtained by a known method) is dissolved in dioxane (50 ml), heated the solution to 80°C and maintained at 80°C for 15 minutes. The solution is slowly cooled to 25°C, maintained for 3 hours at 25°C and the solid separated is filtered to give 9 gm of Form H2 of finasteride.
- Example 4 Example 1 is repeated using Form H2 of finasteride instead of finasteride to give Form H1 of finasteride.
- Example 5 Example 3 is repeated using Form H1 of finasteride instead of finasteride Form H2 of finasteride.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
The present invention relates to novel crystalline forms of finasteride, to processes for their preparation and pharmaceutical compositions containing them.
Description
NOVEL CRYSTALLINE FORMS OF FINASTERIDE
FIELD OF THE INVENTION
The present invention relates to novel crystalline forms of finasteride, to processes for their preparation and pharmaceutical compositions containing them.
BACKGROUND OF THE INVENTION
Finasteride of formula (1) :
or (5α,17β)-N-(1 ,1-Dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide is used for the treatment of benign prostatic hypertrophy and its therapeutic uses are disclosed in US 4,760,071.
Two crystalline forms of finasteride, Form I and Form II, are disclosed in EP 0599376. We have discovered two novel crystalline forms of finasteride. The novel forms have been found to be stable and reproducible. These novel forms do not automatically convert into other crystalline forms of finasteride.
The novel forms of finasteride are, thus, suitable for pharmaceutical preparations. Thus the object of the present invention is to provide stable novel crystalline forms of finasteride, processes for preparation of the novel crystalline forms and pharmaceutical compositions containing these novel crystalline forms.
SUMMARY OF THE INVENTION
According to one aspect of the present invention, there is provided a novel crystalline form of finasteride, designated as Form H1 , characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at about 5.3, 5.8, 6.8, 7.3, 9.0, 9.4, 10.7, 13.9, 14.9, 15.9, 17.3, 18.2, 19.0, 20.1 degrees. Figure 1 shows typical Form H1 x-ray powder diffraction pattern.
According to another aspect of the present invention there is provided a process for preparation of the Form H1 of finasteride comprising the steps of: a) mixing finasteride and an alcohol; b) maintaining at about 4,0°C to 60°C for about 10 minutes to 1 hour; c) cooling slowly to about 0°C to 5°C; d) maintaining for about 1 hour to 3 hours at about 0°C to 5°C; e) filtering the solid separated.
The alcohol is methanol, ethanol or isopropyl alcohol; or mixture thereof.
According to one aspect of the present invention, there is provided a novel crystalline form of finasteride, designated as Form H2, characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at about 5.4, 9.9, 12.1 , 14.5, 15.2, 16.2, 19.3, 29.0 degrees. Figure 2 shows typical Form H2 x-ray powder diffraction pattern.
According to another aspect of the present invention there is provided a process for preparation of the Form H2 of finasteride comprising the steps of. a) dissolving finasteride in dioxane; b) maintaining at about 70°C to 80°C for about 10 minutes to 30 minutes; c) cooling the solution slowly to about 20°C to 25°C; d) maintaining at about 20°C to 25°C for about 2 hours to 4 hours; e) filtering the solid separated. The previously known forms or finasteride prepared by a known method may be used in the above processes.
According to another aspect of the present invention there is provided a pharmaceutical composition comprising Form H1 or Form H2 of finasteride.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a x-ray powder diffraction pattern of Form H1 finasteride. Figure 2 is a x-ray powder diffraction pattern of Form H2 finasteride. x-Ray powder diffraction spectrum was measured on a Siemens diffractometer.
DETAILED DESCRIPTION OF THE INVENTION
According to one aspect of the present invention, there is provided a novel crystalline form of finasteride, designated as Form H1, characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at about 5.3, 5.8,
6.8, 7.3, 9.0, 9.4, 10.7, 13.9, 14.9, 15.9, 17.3, 18.2, 19.0, 20.1 degrees. Figure 1 shows typical Form H1 x-ray powder diffraction pattern.
According to another aspect of the present invention, there is provided a process for preparation of the Form H1 of finasteride. Thus finasteride is mixed with an alcohol. The suitable alcohol is methanol or ethanol or iso propyl alcohol; or mixture thereof. The previously known forms or finasteride prepared by a known method may be used. The contents are maintained at about 40°C to
60°C for about 10 minutes to 1 hour and then cooled slowly in about 3 hours to about 0°C to 5°C. The contents are maintained for about 1 hour to 3 hours at about 0°C to 5°C, preferably for about 1.5 hours at 0°C. The Form H1 of finasteride is separated by filtration.
According to one aspect of the present invention, there is provided a novel crystalline form of finasteride, designated as Form H2, characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at about 5.4, 9.9,
12.1, 14.5, 15.2, 16.2, 19.3, 29.0 degrees. Figure 2 shows typical Form H2 x-ray powder diffraction pattern.
According to another aspect of the present invention there is provided a process for preparation of the Form H2 of finasteride. Thus finasteride is dissolved in dioxane, the solution is heated to about 70°C to 80°C and maintained at this temperature for about 10 minutes to 30 minutes. The solution is cooled slowly, in about 3 hours, to about 20°C to 25°C and maintained at the same temperature for about 2 hours to 4 hours. The separated crystals are
filtered to give Form H2 of finasteride. The previously known forms or finasteride prepared by a known method may be used in the process.
According to another aspect of the present invention there is provided a pharmaceutical composition comprising Form H1 or Form H2 of finasteride. The forms of finasteride may be formulated in a form suitable for oral administration or injection.
The following examples are given for the purpose of illustrating the present invention and should not be considered as limitations on the scope or spirit of the invention.
Example 1 Finasteride (10 gm) (obtained by a known method) is dissolved in methanol (25 ml), heated to 55°C and maintained at this temperature for 15 minutes. The solution is slowly cooled to 0°C in 3 hours and maintained at 0°C for 1.5 hours. The separated crystals are filtered at 0°C to give 8.5 gm of Form H1 of finasteride.
Example 2 Finasteride (10 gm) (obtained by a known method) is dissolved in isopropyl alcohol (40 ml), heated to 55°C and maintained at this temperature for 15 minutes. The solution is slowly cooled to 0°C in 3 hours and maintained at 0°C for 1.5 hours. The separated crystals are filtered at 0°C to give 8.5 gm of Form H1 of finasteride. Example 3
Finasteride (10 gm) (obtained by a known method) is dissolved in dioxane (50 ml), heated the solution to 80°C and maintained at 80°C for 15 minutes. The solution is slowly cooled to 25°C, maintained for 3 hours at 25°C and the solid separated is filtered to give 9 gm of Form H2 of finasteride.
Example 4 Example 1 is repeated using Form H2 of finasteride instead of finasteride to give Form H1 of finasteride.
Example 5
Example 3 is repeated using Form H1 of finasteride instead of finasteride Form H2 of finasteride.
Claims
1. A crystalline Form H1 of finasteride.
2. A crystalline finasteride, characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at about 5.3, 5.8, 6.8, 7.3, 9.0,
9.4, 10.7, 13.9, 14.9, 15.9, 17.3, 18.2, 19.0, 20.1 degrees.
3. A crystalline finasteride, characterized by an x-ray powder diffraction pattern as in figure 1.
4. A process for preparation of Form H1 of finasteride of claim 1 , comprising the steps of: a) mixing finasteride and an alcohol; b) maintaining at about 40°C to 60°C for about 10 minutes to 1 hour; c) cooling slowly to about 0°C to 5°C; d) maintaining for about 1 hour to 3 hours at about 0°C to 5°C; e) filtering the solid separated; wherein the alcohol is methanol or ethanol or isopropyl alcohol.
5. A process according to claim 4, wherein the alcohol is methanol.
6. A process according to claim 4, wherein the alcohol is isopropyl alcohol.
7. A crystalline Form H2 of finasteride. 8. A crystalline finasteride, characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at about 5.4, 9.9, 12.1, 14.5, 15.2, 16.2, 19.3, 29.0 degrees. 9. A crystalline finasteride, characterized by an x-ray powder diffraction pattern as in figure 2. 10. A process for preparation of Form H2 of finasteride of claim 7, comprising the steps of: a) dissolving finasteride in dioxane; b) maintaining at about 70°C to 80°C for about 10 minutes to 30 minutes; c) cooling the solution slowly to about 20°C to 25°C; d) maintaining at about 20°C to 25°C for about 2 hours to 4 hours; e) filtering the solid separated.
11. A pharmaceutical composition comprising the crystalline Form H1 of finasteride of claim 1 and a pharmaceutically acceptable carrier.
2. A pharmaceutical composition comprising the crystalline Form H2 of finasteride of claim 7 and a pharmaceutically acceptable carrier.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2003/000060 WO2004083230A1 (en) | 2003-03-19 | 2003-03-19 | Novel crystalline forms of finasteride |
| AU2003217439A AU2003217439A1 (en) | 2003-03-19 | 2003-03-19 | Novel crystalline forms of finasteride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2003/000060 WO2004083230A1 (en) | 2003-03-19 | 2003-03-19 | Novel crystalline forms of finasteride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004083230A1 true WO2004083230A1 (en) | 2004-09-30 |
Family
ID=33017816
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2003/000060 Ceased WO2004083230A1 (en) | 2003-03-19 | 2003-03-19 | Novel crystalline forms of finasteride |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003217439A1 (en) |
| WO (1) | WO2004083230A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5468860A (en) * | 1992-11-19 | 1995-11-21 | Merck & Co., Inc. | New finasteride processes |
| US5652363A (en) * | 1995-10-05 | 1997-07-29 | C.D. Searle & Co. | Pyrido-1,4-oxazinylalkyl-benzamide derivatives |
-
2003
- 2003-03-19 AU AU2003217439A patent/AU2003217439A1/en not_active Abandoned
- 2003-03-19 WO PCT/IN2003/000060 patent/WO2004083230A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5468860A (en) * | 1992-11-19 | 1995-11-21 | Merck & Co., Inc. | New finasteride processes |
| US5652363A (en) * | 1995-10-05 | 1997-07-29 | C.D. Searle & Co. | Pyrido-1,4-oxazinylalkyl-benzamide derivatives |
Non-Patent Citations (1)
| Title |
|---|
| WAWRZYCKA I., ET AL.: "Structural characterization of polymorphs and molecular complexes to finasteride", JOURNAL OF MOLUCULAR STRUCTURE, vol. 474, 1999, pages 157 - 166, XP000920855 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003217439A1 (en) | 2004-10-11 |
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