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Novel Crystalline Salts Of Voriconazole Useful For Formulations

Abstract: Formula-I where HX is succinic acid, l-hydroxy-2-naphthoic acid, L- (+)-tartaric acid, 3-hydroxy-3-methylglutaric acid (meglutol), formic acid, acetic acid, propionic acid, d, 1-lactic acid benzoic aicd, fumaric acid, and p-toluenesulphonic aicd.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
28 July 2005
Publication Number
36/2007
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
Parent Application

Applicants

NATCO PHARMA LIMITED
NATCO PHARMA LIMITED NATCO HOUSE ROAD NO.2, BANJARA HILLS HYDERABAD.

Inventors

1. DR. KONAKANCHI DURGA PRASAD
NATCO PHARMA LIMITED NATCO HOUSE ROAD NO.2, BANJARA HILLS HYDERABAD.
2. MR. GONGALLA BUCHAPPA
NATCO PHARMA LIMITED NATCO HOUSE ROAD NO.2, BANJARA HILLS HYDERABAD, ANDHRA PRADESH, INDIA PIN: 500 033
3. VENKAIAH CHOWDARY NANNAPANENI
NATCO PHARMA LIMITED NATCO HOUSE ROAD NO.2, BANJARA HILLS HYDERABAD, ANDHRA PRADESH, INDIA PIN: 500 033

Specification

INTRODCTION
The present invention relates to novel salts of Voriconazole, an anti-fungal drug. The present invention further relates to preparation of novel salts of Voriconazole with succinate, xinafoate, L- (+)-tartrate, 3-hydroxy-3-methylglutarate (meglutate), formate, acetate, propionate, d, 1-lactate, benzoate, fumarate, p-toluenesulphonate etc., useful in the preparation of the Voriconazole formulations. The structure of Voriconazole salt, shown in Formula-I is,
where HX is succinic acid, l-hydroxy-2-naphthoic acid, L- (+)-tartaric acid, 3-hydroxy-3-methylglutaric acid (meglutol), formic acid, acetic acid, propionic acid, (d, l)-lactic acid benzoic aicd, fumaric acid, p-toluenesulphonic aicd.

BACKGROUND OF THE INVENTION
Voriconazole is a triazole antifungal agent structurally related to fluconazole. Its antifungal activity and synthesis is reported in Bioorganic & Medicinal Chemistry Letters Vol.6. No. 16, 2011-2036,1996. Voriconazole acts principally by inhitibiting cytochrome P450 14a-demethylase (P45014DM). Thus the conversion of lanosterol to ergosterol is

1. Novel salts of Voriconazole, shown in Formula-I,

Formula-I where HX is succinic acid, 1-hydroxy-2-naphthoic acid, L- (+)-tartaric acid,, 3-hydroxy-3-methylglutaric acid (meglutol), formic acid, acetic acid, propionic acid, d,l-lactic acid, benzoic acid, fumaric acid, p-toluenesulphonic aicd.
2. Crystalline solid Voriconazole succinate of claim 1 further having peaks in the powder X-ray diffraction pattern at 12.697, 13.883, 16.000, 16.583, 17.470, 19.903, 21.270, 26.166, and 28.313.
3. Crystalline solid Voriconazole xinafoate of claim 1 further having peaks in the powder X-ray diffraction pattern at 10.347, 12.162, 12.640, 13.806, 14.788, 15.931, 16.525, 17.403, 19.765, 21.220, 26.150, 26.535, and 28.231
4. Crystalline solid Voriconazole L-(+)-tartrate of claim 1 further having peaks in the powder X-ray diffraction pattern at 5.078, 10.176, and 20.439.
5. Crystalline solid Voriconazole meglutate of claim 1 further having peaks in the powder X-ray diffraction pattern at 6.825, 13.759, 16.480,17.350, and 19.715.
6. A Process for the prearation of the salts of Voriconazole of claim 1 comprising:
a) dissolving the Voriconazole in a warm organic solvent such as methanol, ethanol, isopropyl alcohol, t-butanol, n-butanol, toluene, xylene, acetone, methyl ethyl

ketone, methyl isobutyl ketone, ethyl acetate, cyclohexane, methylene chloride, chloroform, etc.
b) then adding molar equivalent quantity of the respective organic acid
c) isolating the acid addition salt either by crystallization from the solvent used or by distilling of solvent used in the process
d) drying the wet salt to get the pharmaceutically useful salts of Voriconazole.
7. A pharmaceutical formulation using the Voriconazole salts according to claim 1. Dated this 14th day of July, 2006

Documents

Application Documents

# Name Date
1 1027-CHE-2005 CORRESPONDENCE OTHERS 31-03-2010.pdf 2010-03-31
1 1027-CHE-2005_EXAMREPORT.pdf 2016-07-02
2 1027-che-2005-abstract.pdf 2011-09-03
2 1027-CHE-2005 AMANDED PAGES OF SPECIFICATION 31-03-2010.pdf 2010-03-31
3 1027-che-2005-claims.pdf 2011-09-03
3 1027-CHE-2005 AMANDED CLAIMS 31-03-2010.pdf 2010-03-31
4 1027-CHE-2005 CORRESPONDENCE OTHERS 12-11-2010.pdf 2010-11-12
4 1027-che-2005-correspondence others.pdf 2011-09-03
5 abs-1027.jpg 2011-09-03
5 1027-che-2005-discription complete.pdf 2011-09-03
6 abs-1027-che-2005.jpg 2011-09-03
6 1027-che-2005-form1.pdf 2011-09-03
7 1027-che-2005-form5.pdf 2011-09-03
8 abs-1027-che-2005.jpg 2011-09-03
8 1027-che-2005-form1.pdf 2011-09-03
9 abs-1027.jpg 2011-09-03
9 1027-che-2005-discription complete.pdf 2011-09-03
10 1027-CHE-2005 CORRESPONDENCE OTHERS 12-11-2010.pdf 2010-11-12
10 1027-che-2005-correspondence others.pdf 2011-09-03
11 1027-CHE-2005 AMANDED CLAIMS 31-03-2010.pdf 2010-03-31
11 1027-che-2005-claims.pdf 2011-09-03
12 1027-che-2005-abstract.pdf 2011-09-03
12 1027-CHE-2005 AMANDED PAGES OF SPECIFICATION 31-03-2010.pdf 2010-03-31
13 1027-CHE-2005_EXAMREPORT.pdf 2016-07-02
13 1027-CHE-2005 CORRESPONDENCE OTHERS 31-03-2010.pdf 2010-03-31