WO1998056773A1 - Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and its use as antiepileptic - Google Patents
Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and its use as antiepileptic Download PDFInfo
- Publication number
- WO1998056773A1 WO1998056773A1 PCT/EP1998/003428 EP9803428W WO9856773A1 WO 1998056773 A1 WO1998056773 A1 WO 1998056773A1 EP 9803428 W EP9803428 W EP 9803428W WO 9856773 A1 WO9856773 A1 WO 9856773A1
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- WIPO (PCT)
- Prior art keywords
- weak
- modification
- medium
- strong
- triazole
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
Definitions
- Example 4 Valuable pharmacological properties are attributed to this compound; thus, it can be used, for example, as an antiepileptic.
- the compound 1- (2,6-dif luorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide is obtained according to EP 199262, starting from 2,6-difluorobenzyl azide via the formation of 1-(2,6-difluorobenzyl)-1 H-1 ,2,3- triazole-4-carboxylic acid, the procedure being analogous to Example 2.
- EP 199262 provides no information at all about possible crystal modifications obtained. If the method according to Example 4 is used in conjunction with Example 2, the crude 1 -(2,6- difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide product obtained is finally crystallized from ethanol. However, EP 199262 gives no indication that such recrystallization is specifically to be applied, or on particular conditions that might be adopted. It has now surprisingly been found that the different crystal modifications (polymorphism) characterized below can be prepared by choice of specially selected process conditions, for example through the choice of an appropriate solvent for the recrystallization or the duration of the recrystallization. Description of the invention
- 1-(2,6-Difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide can be obtained in the novel crystal modifications A, A', B and C. These crystal modifications differ with respect to their thermodynamic stability, in their physical parameters, such as the absorption pattern of IR and Raman spectra, in X-ray structure investigations and in their preparation processes.
- the invention relates to the novel crystal modifications B and C, their preparation and use in pharmaceutical preparations comprising this crystal modification.
- the modification A' compared with A, has defects in the crystal lattice. These are detectable, for example, by X-ray analysis, e.g. by smaller line spacings with otherwise predominantly identical lines or bands.
- the crystal modification A of 1 -(2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide melts at 242°C (239-245°C).
- modification A or A' differs from modifications B and C predominantly in the shape and in the relative intensity of many bands. Particularly characteristic are the bands at 3412 cm '1 and 3092 cm “1 [cf. Figure 1], which are not present in the FT-IR spectra of the modifications B and C. In the range 4000-600 cm '1 , inter alia the following bands are obtained for modification A: 3412, 3189, 3092, 1634, 1560, 1473, 1397, 1325, 1300, 1284, 1235, 1125, 1053, 1036, 1014, 885, 840, 799, 781 , 723, 688 and 640 cm "1 .
- the apparatus IFS 88 (Bruker) can be used for recording of each of the FT-IR spectra.
- the modification A or A' differs from modifications B and C predominantly in the shape and in the relative intensity of many bands. Particularly characteristic are the band at 1080 cm '1 [cf. Figure 2], which is not present in the Raman spectra of the modifications B and C. In the range 3400-300 cm '1 , inter alia the following bands are obtained for the modification A: 3093, 2972, 1628, 1614, 1558, 1465, 1446, 1393, 1279, 1245, 1147, 1080, 1061 , 1036, 1014, 840, 724, 691 , 667, 550, 499, 437 and 368 cm '1 .
- the apparatus RFS 100 (Bruker) can be used for recording of each of the FT Raman spectra.
- the modification A has an X-ray powder pattern with characteristic lines with interplanar spacings (d values) of 10.5 A, 5.14 A, 4.84 A, 4.55 A, 4.34 A, 4.07 A, 3.51 A, 3.48 A, 3.25 A, 3.19 A, 3.15 A, 3.07 A, 2.81 A [cf. Table 1].
- the patterns recorded on X-ray film were measured using an LS-18 line scanner from Johannsson, Taby (Sweden) and evaluated using the Scanpi software (P.E.Werner, University of Sweden).
- Characteristic for the modification A is the thermogram in differential scanning calorimetry. It has an endothermic peak in the range from 230°C to 260°C. The peak temperature is 239- 245°C, and the endothermic signal is 209 J/g +/- 10 J/g. The measurement was carried out on a Perkin Elmer DSC 7 in a closed pan with a heating rate of 20 K/minute. The typical sample quantity is about 4 mg. As a typical distinguishing feature compared with the modifications B and C, the thermogram of the modification A has no further thermal signal.
- Crystals of the modification A' have the same crystal structure as modification A. They differ from the modification A in the X-ray powder pattern in that they have slightly smaller line spacings between specific pairs of lines. These are the pairs of lines with the following interplanar spacings: 3.68 A and 3.64 A, 3.51 A and 3.48 A, 3.19 A and 3.15 A.
- the novel modification B differs from the modification A or A' and C predominantly in the shape and in the relative intensity of many bands. Particularly characteristic is a band at 1678 cm "1 [cf . Figure 1 ], which is not to be observed in the corresponding spectra of the modifications A and C.
- the following bands are obtained for the modification B: 3404, 3199, 3125, 1678, 1635, 1560, 1475, 1393, 1357, 1322, 1286, 1237, 1051 , 1036, 1028, 889, 837, 800, 719, 667 and 645 cm "1 .
- the apparatus IFS 85 (Bruker) can be used for recording of each of the FT-IR spectra.
- the novel modification B differs from the modifications A or A' and C predominantly in the shape and in the relative intensity of many bands. Particularly characteristic are the bands at 3166 cm “1 and 1086 cm '1 [cf. Figure 2], which are not present in the Raman spectra of the modifications A and C.
- the following bands are obtained for the modification B: 3166, 3089, 2970, 1678, 1628, 1614, 1559, 1464, 1441 , 1391 , 1275, 1244, 1147, 1086, 1062, 1036, 1014, 839, 773, 724, 690, 668, 595, 549, 500, 493, 430 and 365 cm '1 .
- the apparatus RFS 100 (Bruker) can be used for recording of each of the FT Raman spectra.
- the novel modification B has an X-ray powder pattern with characteristic lines with interplanar spacings (d values) of 11.0 A, 8.3 A, 5.18 A, 4.88 A, 4.80 A, 4.42 A, 4.33 A, 4.19 A, 4.12 A, 3.81 A, 3.50 A, 3.41 A, 3.36 A, 3.32 A, 3.28 A, 3.24 A, 3.05 A, 2.83 A [cf. Table U-
- the novel modification B has, in addition to an endothermic signal in the range from 230°C to 260°C (peak temperature 239- 245°C), a weak thermal signal at 205°C (180° - 220°C) as a typical distinguishing feature compared with the modifications A or A' and C.
- the novel modification C differs from the modifications A or A' and B predominantly in the shape and in the relative intensity of many bands. Particularly characteristic is a band at 3137 cm “1 [cf. Figure 1], which is not to be observed in the corresponding spectra of the modifications A and B. In the range 4000-600 cm " , inter alia the following bands are obtained for the novel modification C: 3396, 3287, 3137, 1657, 1631 , 1602, 1559, 1475, 1392, 1323, 1287, 1237, 1122, 1104, 1047, 1035, 1012, 876, 839, 797, 773, 729 and 653 cm "1 .
- the apparatus IFS 85 (Bruker) can be used for recording of each of the FT-IR spectra.
- the modification C differs from the modifications A or A' and B predominantly in the shape and in the relative intensity of many bands. Particularly characteristic are the bands at 3137 cm '1 and 1602 cm “1 [cf. Figure 2], which are not present in the Raman spectra of the modifications A and B.
- the following bands are obtained for the modification C: 3137, 3080, 3012, 2971 , 1673, 1629, 1602, 1561 , 1436, 1271 , 1248, 1105, 1065, 1035, 1013, 839, 800, 767, 726, 690, 672, 593, 549, 500, 492, 435 and 370 cm '1 .
- the apparatus RFS 100 (Bruker) can be used for recording of each of the FT Raman spectra.
- the novel modification C has an X-ray powder pattern with characteristic lines with interplanar spacings (d values) of 9.0 A, 4.73 A, 4.65 A, 3.75 A, 3.54 A, 3.42 A, 3.25 A [cf . Table 1 ].
- the modification C has, in addition to an endothermic signal in the range of 230°C to 260°C (peak temperature 239- 245°C), a very broad, weak, exothermic signal in the region of 180°C compared with the modifications A or A' and B.
- Modifications A, A', B and C have valuable pharmacological properties; in particular, they can be used for the treatment of epilepsy.
- modification B has a substantially faster dissolution rate in water and gastric fluid than modification A or A'. Consequently, when modification B is used therapeutically, a rapid onset of action is achieved, which is particularly advantageous, for example in an acute epilepsy attack.
- the invention relates to the modification B of 1-(2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4- carboxamide, having the following absorption in the infrared spectrum (KBr pellet - transmission method): band at 1678 cm '1 .
- the invention relates to the modification B of 1 -(2,6-dif luorobenzyl)-1 H-1 ,2,3-triazole-4- carboxamide, having characteristic lines with interplanar spacings (d values) of 11.0 A, 8.3 A, 5.18 A, 4.88 A, 4.80 A, 4.42 A, 4.33 A, 4.19 A, 4.12 A, 3.81 A, 3.50 A, 3.41 A, 3.36 A, 3.32 A, 3.28 A, 3.24 A, 3.05 A and 2.83 A, determined by means of an X-ray powder pattern.
- the invention relates to the modification B of 1-(2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4- carboxamide, having the characteristic lines with interplanar spacings (d values) as shown in Table 1.
- the invention relates to the modification B of 1 -(2,6-dif luorobenzyl)-1 H-1 ,2,3-triazole-4- carboxamide, having in the thermogram in differential scanning calorimetry a weak thermal signal at 205°C (180-220°C) in addition to an endothermic signal in the range from 230°C to 260°C (peak temperature 239-245°C).
- the invention furthermore relates to the crystal modification C of 1 -(2,6-difluorobenzyl)-1 H- 1 ,2,3-triazole-4-carboxamide, having the following absorption in the infrared spectrum (KBr pellet - transmission method): band at 3137 cm '1 .
- the invention relates to the modification C of 1-(2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4- carboxamide, having characteristic lines with interplanar spacings (d values) of 9.0 A, 4.73 A, 4.65 A, 3.75 A, 3.54 A, 3.42 A, 3.25 A, determined by means of an X-ray powder pattern.
- the invention relates to modification C of 1 -(2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4-carbox- amide, having the characteristic lines with interplanar spacings (d values) as shown in Table 1.
- the invention relates to the modification C of 1 -(2,6-dif luorobenzyl)-1 H-1 ,2,3-triazole-4- carboxamide, having in the thermogram in differential scanning calorimetry a very broad weak exothermic signal in the region of 180°C, in addition to an endothermic signal in the range from 230°C-260°C (peak temperature 239-245°C).
- the invention relates to the essentially pure forms of the modifications B and C of 1-(2,6- difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide.
- the term "essentially pure form” means purity of >95%, in particular >98%, primarily >99%, based on the modifications B and C.
- the invention relates to pharmaceutical preparations comprising the modifications B and C of 1 -(2,6-dif luorobenzyl)-1 H-1 , 2, 3-triazole-4-carboxamide.
- the invention relates in particular to corresponding pharmaceutical preparations for the treatment of epilepsy and subindications thereof.
- the invention relates to the use of the modifications B and C of 1 (2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide for the preparation of pharmaceutical preparations, in particular for the treatment of epilepsy and subindications thereof.
- novel modifications B and C of 1-(2,6-difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide can be used, for example, in the form of pharmaceutical preparations which comprise a therapeutically effective amount of the active ingredient, if desired together with inorganic or organic, solid or liquid, pharmaceutically usable carriers, which are suitable for enteral, for example oral, or parenteral administration.
- novel modifications B and C of 1 -(2,6-dif iuorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide can be used in the form of preparations which can be administered parenterally or of infusion solutions.
- the pharmaceutical preparations may be sterilized and/or may comprise excipients, for example preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, salts for regulating the osmotic pressure and/or buffers.
- excipients for example preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, salts for regulating the osmotic pressure and/or buffers.
- the present pharmaceutical preparations comprise from about 0.1% to 100%, in particular from about 1% to about 50%, of lyophilisates to about 100% of the active ingredient.
- the invention also relates to the use of the modifications B and C of 1 -(2,6-difluorobenzyl)- 1 H-1 ,2,3-triazole-4-carboxamide as a drug, preferably in the form of pharmaceutical preparations.
- the dosage may depend on various factors, such as method of administration, species, age and/or individual condition.
- the doses to be administered daily are between about 0.25 and about 10 mg/kg in the case of oral administration, and preferably between about 20 mg and about 500 mg for warm-blooded species having a body weight of about 70 kg.
- 1-(2,6-Difluorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide (15.0 g) is dissolved in acetic acid (120 ml) at about 90°C while stirring. The solution is cooled to 20°C in the course of about 8 minutes, a suspension forming. The product is immediately isolated by filtration, washed with toluene (120 ml) and dried in vacuo at about 60°C. 10.1 g of the product are obtained as modification C. Yield 67.3%.
- Film-coated tablets each containing, for example, 100, 200 or 400 mg of the modification B or C of 1 -(2,6-dif luorobenzyl)-1 H-1 ,2,3-triazole-4-carboxamide with the following composition per dosage unit:
- Titanium dioxide 0.83 1.66 3.32
- the active ingredient is granulated with demineralized water. Milled lactose, maize starch, Avicel PH 102, cellulose-HP-M-603 and sodium laurylsulfate are added to the above mixture and granulated with demineralized water.
- the moist material is dried and milled. After the addition of the remaining ingredients, the homogeneous mixture is compressed to give tablet cores having the stated active ingredient content.
- the tablet cores are coated with the film coat which is formed from the appropriate ingredients, the latter being dissolved or being suspended in water or in small amounts of ethanol with 5% of isopropanol.
- Figure 1 shows the FT-IR spectra of the KBr pellets of crystal modifications A, B and C.
- Figure 2 shows the FT-Raman spectra of the powder of modifications A, B and C.
Abstract
Description
Claims
Priority Applications (17)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP53628998A JP3672575B2 (en) | 1997-06-10 | 1998-06-08 | Drug crystal deformation |
EP98934930A EP0994864B1 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and its use as antiepileptic |
PL330798A PL192114B1 (en) | 1997-06-10 | 1998-06-08 | Crystalline form of a pharmaceutic agent |
NZ331370A NZ331370A (en) | 1997-06-10 | 1998-06-08 | Crystal modification B and C of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide and use thereof |
DE69813560T DE69813560T2 (en) | 1997-06-10 | 1998-06-08 | CRYSTAL MODIFICATION OF 1- (2,6-DIFLUORBENZYL) -1H-1,2,3-TRIAZOL-4-CARBONIC ACID AMIDE AND ITS USE AS AN ANTI-PILEPTIC |
AT98934930T ATE237599T1 (en) | 1997-06-10 | 1998-06-08 | CRYSTAL MODIFICATION OF 1-(2,6-DIFLUORBENZYL)-1H-1,2,3-TRIAZOLE-4-CARBON AUREAMIDE AND ITS USE AS AN ANTI-EPILEPTIC |
IL12573298A IL125732A (en) | 1997-06-10 | 1998-06-08 | Crystal modification of the compound 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and a pharmaceutical composition for treating epilepsy comprising the same |
SK1094-98A SK283734B6 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of compound 1-(2,6-difluorobenzyl)-1H-1,2,3- triazole-4-carboxamide, pharmaceutical compositions containing them and use thereof |
AU84372/98A AU725517B2 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1H-1,2,3- triazole-4-carboxamide and its use as antiepileptic |
CA002256015A CA2256015C (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and its use as antiepileptic |
HU0002113A HU225153B1 (en) | 1997-06-10 | 1998-06-08 | Crystal modifications of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide, their use and pharmaceutical compositions containing them |
BR9804946A BR9804946A (en) | 1997-06-10 | 1998-06-08 | Crystal modification of a pharmaceutical agent |
SI9830450T SI0994864T1 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and its use as antiepileptic |
DK98934930T DK0994864T3 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1- (2,6-difluorobenzyl) -1H-1,2,3-triazole-4-carboxamide and its use as an antiepileptic |
NO19983666A NO329314B1 (en) | 1997-06-10 | 1998-08-11 | Crystal modification of a pharmaceutical agent, its use, and pharmaceutical composition containing the crystal modification. |
HK00106807A HK1028242A1 (en) | 1997-06-10 | 2000-10-25 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3,-triazole-4-carboxamide and its use as antiepileptic |
HK00107340A HK1028031A1 (en) | 1997-06-10 | 2000-11-17 | Crystal modification of 1-(2,6-difluorobenzyl)-IH-1,2,3-triazole-4-carboxamide and its use as antiepileptic. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH140497 | 1997-06-10 | ||
CH1404/97 | 1997-06-10 |
Related Child Applications (2)
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US12533098A A-371-Of-International | 1997-06-10 | 1998-09-08 | |
US59968800A Continuation | 1997-06-10 | 2000-06-22 |
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WO1998056773A1 true WO1998056773A1 (en) | 1998-12-17 |
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1998/003428 WO1998056773A1 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3-triazole-4-carboxamide and its use as antiepileptic |
PCT/EP1998/003427 WO1998056772A1 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3--triazole-4-carboxamide and its use as antiepileptic |
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PCT/EP1998/003427 WO1998056772A1 (en) | 1997-06-10 | 1998-06-08 | Crystal modification of 1-(2,6-difluorobenzyl)-1h-1,2,3--triazole-4-carboxamide and its use as antiepileptic |
Country Status (37)
Country | Link |
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US (6) | US6740669B1 (en) |
EP (2) | EP0994863B1 (en) |
JP (2) | JP3672575B2 (en) |
KR (2) | KR100409168B1 (en) |
CN (3) | CN1298708C (en) |
AR (4) | AR012945A1 (en) |
AT (2) | ATE232852T1 (en) |
AU (2) | AU725517B2 (en) |
BR (2) | BR9804946A (en) |
CA (3) | CA2614926C (en) |
CO (2) | CO4940448A1 (en) |
CY (1) | CY2007014I2 (en) |
CZ (2) | CZ292481B6 (en) |
DE (3) | DE69811500T2 (en) |
DK (2) | DK0994863T3 (en) |
ES (2) | ES2192779T3 (en) |
FR (1) | FR07C0037I2 (en) |
HK (3) | HK1028241A1 (en) |
HU (2) | HU225153B1 (en) |
ID (2) | ID21014A (en) |
IL (2) | IL125733A (en) |
LU (1) | LU91345I2 (en) |
MY (2) | MY120156A (en) |
NL (1) | NL300284I2 (en) |
NO (2) | NO329314B1 (en) |
NZ (2) | NZ331370A (en) |
PE (2) | PE79799A1 (en) |
PL (2) | PL191943B1 (en) |
PT (1) | PT994864E (en) |
RU (2) | RU2198167C2 (en) |
SI (2) | SI0994863T1 (en) |
SK (2) | SK283734B6 (en) |
TR (2) | TR199801631T1 (en) |
TW (2) | TW526195B (en) |
UY (1) | UY25844A1 (en) |
WO (2) | WO1998056773A1 (en) |
ZA (2) | ZA984967B (en) |
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US7750028B2 (en) | 1997-06-10 | 2010-07-06 | Novartis Ag | Crystal modifications of 1-(2,6-difluorobenzyl)-1H-1, 2,3-triazole-4-carboxamide |
ITMI20110718A1 (en) * | 2011-04-29 | 2012-10-30 | Dipharma Francis Srl | PROCEDURE FOR PURIFICATION OF RUFINAMIDE |
US8884026B2 (en) | 2010-04-30 | 2014-11-11 | Laboratorios Lesvi, S.L. | Process for preparing rufinamide intermediate |
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US20090069390A1 (en) * | 2007-09-12 | 2009-03-12 | Protia, Llc | Deuterium-enriched rufinamide |
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IT1395736B1 (en) * | 2009-08-04 | 2012-10-19 | Dipharma Francis Srl | CRYSTALLINE FORMS OF RUFINAMIDE |
RU2594155C2 (en) * | 2009-09-04 | 2016-08-10 | Тэктикал Терапеутикс, Инк | Novel compositions and methods of producing 5-amino- or substituted amino-1,2,3-triazoles and triazole-orotate compositions |
EP2465853A1 (en) * | 2010-12-14 | 2012-06-20 | Laboratorios Lesvi, S.L. | Polymorph of rufinamide and process for obtaining it |
WO2014013511A2 (en) * | 2012-07-20 | 2014-01-23 | Hetero Research Foundation | Rufinamide solid dispersion |
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US7750028B2 (en) | 1997-06-10 | 2010-07-06 | Novartis Ag | Crystal modifications of 1-(2,6-difluorobenzyl)-1H-1, 2,3-triazole-4-carboxamide |
US8076362B2 (en) | 1997-06-10 | 2011-12-13 | Novartis Ag | Crystal modification A of 1-(2,6-difluorobenzyI)-1 H-1,2,3-triazole-4-carboxamide and dosage forms and formulations thereof |
US8884026B2 (en) | 2010-04-30 | 2014-11-11 | Laboratorios Lesvi, S.L. | Process for preparing rufinamide intermediate |
ITMI20110718A1 (en) * | 2011-04-29 | 2012-10-30 | Dipharma Francis Srl | PROCEDURE FOR PURIFICATION OF RUFINAMIDE |
EP2518057A1 (en) * | 2011-04-29 | 2012-10-31 | Dipharma Francis S.r.l. | Process for the purification of rufinamide |
US8461190B2 (en) | 2011-04-29 | 2013-06-11 | Dipharma Francis S.R.L. | Process for the purification of rufinamide |
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