GB2270521A - Crystalline monohydrate of 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol - Google Patents
Crystalline monohydrate of 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol Download PDFInfo
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- GB2270521A GB2270521A GB9318592A GB9318592A GB2270521A GB 2270521 A GB2270521 A GB 2270521A GB 9318592 A GB9318592 A GB 9318592A GB 9318592 A GB9318592 A GB 9318592A GB 2270521 A GB2270521 A GB 2270521A
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- triazol
- monohydrate
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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
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The monohydrate of 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol is useful for pharmaceutical formulation as an antifungal agent. It is less bitter than the non-hydrated compound and is stable under normal processing conditions.
Description
CRYSTALLINE MONOHYDRATE OF 2-(2.4-Dl FLUOROPHENYL)- 1 ,3-BIS(1 H-1,2,4-TRIAZOL-1 -YL)PROPAN-2-OL Background of the Invention
The present invention is directed to a novel crystalline monohydrate of 2-(2,4 difluorophenyl).i ,3-bis(l H-1,2,4-triazol-1 -yl)propan-2-ol having advantageous properties for pharmaceutical formulation as an antifungal agent, a pharmaceutical composition containing said monohydrate and a method of treatment comprising administering said monohydrate.
Richardson, U.S. Patent No. 4,404,216, which is incorporated herein by reference, has disclosed said 2-(2,4-difl uorophenyl)- 1 ,3-bis(i H-1 ,2,4-triazol- 1 -yl)propan2-ol, of the formula
or a pharmaceutically acceptable salt as an especially preferred compound for use as an antifungal agent.
The compound of formula I is known for its bitter taste and previous taste masking techniques using various sweeteners, amino acids, acids, flavors and adsorbents have been unsuccessful in masking said bitterness.
Summary of the Invention
The present invention comprises the monohydrate form of 2-(2.4-difluorophenyl)- 1,3bis(1 H-l ,2,4-triazol-1-yl)propan-2-ol (hereafter "the monohydrate') which possesses valuable and unobvious properties. Thus, this monohydrate is less bitter, and stable under normal processing conditions for formulation into ceWabieTho-z-eriqe, and fastdissolving conventional dosage forms such as capsules and tablets.
Brief Description of the Drawings
Fig. 1 is the structure of the monohydrate based on single crystal X-ray crystallography, showing that the water molecule of the monohydrate, designated as 01w, is adjacent to one of the triazole moieties of the compound of formula I.
Detailed Description of the Invention
The compound of the present invention is readily prepared by dissolving 2-(2,4difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol compound in hot water and cooling the resulting solution to room temperature thus precipitating the monohydrate in the form of acicular shaped crystals. In contrast to the anhydrous form of the compound of formula 1, the monohydrate is less bitter.
The present monohydrate may be administered as an antifungal agent as described in above-mentioned U.S. Patent 4,404,216. Administration to a human subject may be alone or, preferably, in combination with pharmaceutically acceptable carriers or diluents in a pharmaceutical composition, in accordance with standard pharmaceutical practice. The monohydrate may be administered orally or parenterally including intravenously or intramuscularly. Suitable pharmaceutical carriers include solid diluents or fillers, sterile aqueous solutions and various organic solvents. The pharmaceutical compositions are then readily administered in a variety of dosage forms, such as tablets1 powders, lozenges, syrups, and injectable solutions. These pharmaceutical compositions, if desired, may contain additional ingredients such as flavorings, binders and excipients.Thus, for purposes of oral administration, tablets containing various excipients such as sodium citrate, calcium carbonate and calcium phosphate may be employed along with various disintegrants such as starch, alginic acid and certain complex silicates, together with binding agents such as polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often useful for tabletting purposes. Solid compositions of a similar type may also be employed as fillers in soft and hard filled gelatin capsules. Preferred materials for this include lactose or milk sugar and high molecular weight polyethylene glycols.When an aqueous suspensions or elixirs are desired for oral administration, the essential active ingredient therein may be combined with various sweetening or flavouring agents, coloring matter or dyes and, if desired, emulsifying or suspending agents, together with diluents such as water, ethanol, propylene glycol, glycerin and combinations thereof.
For parenteral administration, solution of the monohydrate in sesame or peanut oil, aqueous propylene glycol, or in sterile aqueous solution may be employed. Such aqueous solutions should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. The sterile aqueous media employed are all readily available by standard techniques known to those skilled in the art.
The effective dosage for the monohydrate depends on the intended route of administration and other factors such as age and weight of the subject, as generally known. For oral administration to human patients, the effective dosage for the monohydrate will be 0.1 to 5.0 mg/kg per day. Thus, tablets can generally be expected to contain anywhere from approximately 5.0 to 500 mg of the monohydrate.
EXAMPLE 1 2-(2.4-difluorophenVI)-1 .3-bis(1 H-l .2.4-triazol-1 -vlropan-2-ol monohvdrate Anhydrous 2-(2,4-difluorophenyl)-1 ,3-bis(l H-i ,2,4-triazol-1 -yl)propan-2-ol (10 grams) was added to de-ionized water (100 ml) while stirring with a magnetic stirring bar. The water was heated to 950C to completely dissolve the 2-(2,4-difluorophenyl) 1,3-bis(l H-1,2,4-triazol-l -yl)propan-2ol. Stirring was continued for 5 minutes. The solution was then allowed to cool to room temperature (approximately 250C) without stirring. Upon standing, precipitates of 2-(2,4-difluorophenyl)-1 ,3-bis(1 H-1,2,4-triazol-1 H-1 ,2,4-triazol-1- yl)propan-2-ol monohydrate were formed as acicular shaped crystals.The solution was allowed to stand for one additional hour at room temperature. The 2-(2,4 difluorophenyl)-l ,3-bis(l H-1 ,2,4-triazol-1-yl)propan-2-ol monohydrate crystals were filtered on a fritted glass filter (10-20 micron) with room air pulled through the filter by vacuum for 24 hours, mp 13800. The water content in the 2-(2.4-difluorophenyl)-1 ,3- bis(1 H-1 ,2,4-triazol-1-yl)propan-2-ol monohydrate was found to be 5.60% by the
Mitsubishi Moisture Meter. This water content corresponded approximately to one water molecule per 2-(2,4-difluorophenyl)-1 ,3-bis(1 H-i ,2,4-triazol-1 -yl)propan-2-ol molecule. The water content of the anhydrous 2-(2,4-difluorophenyl)-1 ,3-bis(1 H-1,2,4triazol-1 -yl)propan-2-ol, used as the starting material, was found to be 0.1%. Anal. Calc.
for Cl3Hl4N602F2: C, 48.15; H, 4.35; N, 25.90. Found: C, 48.48; H, 4.09; N, 25.98.
Mp 13800.
EXAMPLE 2 2-(2 .4-difluorophenyl)-1 .3-bis(1 H-i .2.4-triazol-1 -vl)rnpan-2-oI monohydrate
Anhydrous 2-(2,4-difluorophenyl)-1 ,3-bis( 1 H-i ,2,4-triazol-1 -yl)propan-2-ol (100 grams) was added slowly to deionized water (1300 ml) upon stirring with a magnetic stirring bar to form a slurry. Stirring of the slurry at room temperature was continued for one hour. The slurry was then filtered on a fritted glass filter (10-20 micron) under vacuum. The 2-(2,4-difluorophenyl)-1 ,3-bis(1 H-1,2,4-triazol-l -yl)propan-2-ol monohydrate crystals were dried on the fritted glass filter (10-20 micron) with room air pulled through the filter by vacuum for 24 hours, mp 1380C.The water content in the 2-(2,4-difluorophenyl)-1,3-bis(1 H-1,2,4-triazol-l -yl)propan-2-ol monohydrate was found to be 5.76% by the Karl Fischer Titration method. This water content corresponded approximatelyto one watermolecule per2-(2,4-difluorophenyl)-1 ,3-bis(1 H-t ,2,4-triazol-1 yl)propan-2-ol molecule. The water content in the anhydrous 2-(2,4-difluorophenyl)-1 ,3- bis(1 H-1,2,4-triazol-1 -yl)propan-2-ol was found to be 0.1%. Anal. Calc. for C13H14N6O2F C, 48.15; H, 4.35; N, 25.90. Found: C, 47.90; H, 4.17; N, 25.59.
The following tables illustrate the spectrometric differences between the anhydrous and the monohydrate compounds:
Table 1: Power X-ray diffraction study of the monohydrate.
No. 2Theta d Rel 1 (%) Max 1 Inter 1 Width Type
Range #1
1 5.042 17.5267 4.5 158. 67.21 0.155 KA
2 8.001 11.0502 2.6 91. 38.72 0.176 KA
3 8.441 10.4752 1.1 37. 15.81 0.227 KA
4 9.242 9.5690 11.8 411. 174.82 0.200 KA
5 10.080 8.7753 100.0 3470. 1477.15 0.200 KA
6 12.200 7.2548 1.8 63. 26.68 0.166 KA
7 12.724 6.9571 2.1 73. 30.92 0.163 KA
8 13.860 6.4730 10.5 363. 154.38 0.187 KA
9 15.122 5.8589 12.7 440. 187.30 0.202 KA 10 15.441 5.7385 9.2 321. 136.46 0.169 KA
11 16.240 5.4580 32.9 1140. 485.31 0.205 KA
12 16.639 5.3280 90.2 3131. 1332.98 0.243 KA
No. 2Theta d Re 1 (%) Max I Inter 1 Width Type
Range #;1
13 17.721 5.0050 2.8 96. 41.01 0.255 KA
14 18.368 4.8302 0.9 31. 13.13 D.140 KA
15 18.920 4.6905 3.5 123. 52.21 0.187 KA
16 20.160 4.4047 58.9 2045. 870.66 0.244 KA
17 20.561 4.3197 14.4 500. 213.03 0.203 KA
18 21.199 4.1911 18.1 626. 266.64 0.234 KA
19 22.080 4.0258 5.7 199. 84.64 0.273 KA
20 22.961 3.8733 1.3 45. 19.31 0.110 KA
21 23.201 3.8338 1.1 39. 16.42 0.150 KA
22 23.681 3.7571 2.4 83. 35.37 0.191 KA
23 24.032 3.7031 8.8 306. 130.19 0.145 KA
24 25.083 3.5502 6.6 229. 97.59 0.281 KA
25 25.721 3.4636 17.7 616. 262.15 0.246 KA
26 26.401 3.3759 2.2 77. 32.91 0.118 KA
27 27.204 3.2781 4.2 147. 62.55 0.126 KA
28 27.520 3.2411 9.6 332. 141.19 0.206 KA
29 28.043 3.1819 2.1 73. 31.13 0.100 KA
30 28.398 3.1429 1.9 65. 27.51 0.179 KA
31 28.879 3.0916 2.6 91. 38.59 0.141 KA
32 29.359 3.0422 16.4 568. 241.93 0.274 KA
33 30.161 2.9631 2.3 81. 34.64 0.129 KA
34 30.399 2.9404 4.0 139. 59.09 0.245 KA
35 31.202 2.8665 1.3 45. 19.12 0.152 KA
36 31.518 2.8385 0.8 29. 12.42 0.134 KA
37 32.522 2.7532 2.0 69. 29.55 0.169 KA
38 34.878 2.5724 1.9 65. 27.87 0.299 KA
39 36.120 2.4867 2.4 84. 35.70 0.190 KA
40 37.680 2,3873 0.5 19. 8.07 0.212 KA
41 39.205 2.2979 0.6 20. 8.33 0.129 KA
Table 2: Power X-ray diffraction study of the anhydrous compound.
No. 2Theta d Re 1 (%) Max 1 Inter 1 Width Type
Range #1
1 4.717 18.7534 0.3 32. 13.77 0.150 KA
2 7.407 11.9430 3.3 310. 132.04 0.194 KA
3 11.640 7.6025 8.1 771. 328.32 0.191 KA
4 12.124 7.3001 0.7 65. 27:64 0.157 KA
5 13.364 6.6254 1.3 120. 51.02 0.180 KA
6 14.279 6.2028 2.9 274. 116.76 0.167 KA
7 14.802 5.9848 70.8 6714. 2858.69 0.190 KA
8 15.761 5.6227 15.5 1468. 624.79 0.187 KA
9 17.323 5.1191 33.1 3136 1335.18 0.165 KA
10 18.200 4.8744 1.9 176. 74.75 0.115 KA
11 18.518 4.7914 15.3 1455. 619.65 0.165 KA
12 19.560 4.5384 16.8 1591. 677.46 0.172 KA
13 19.719 4.5022 16.0 1516. 645.38 0.217 KA
14 20.083 4.4214 8.1 767. 326.51 0.156 KA
15 22.239 3.9974 3.7 352. 149.70 0.198 KA
16 23.920 3.7201 3.7 356. 151.43 0.161 KA
17 24.439 3.6423 100.0 9487. 4039.22 0.192 KA
18 24.960 3.5674 5.3 504. 214.78 0.202 KA
19 25.362 3.5118 2.0 185. 78.97 0.146 KA
20 25.762 3.4582 2.3 213. 90.89 0.161 KA
21 26.240 3.3963 4.5 432. 183.71 0.197 KA
22 26.879 3.3169 13.9 1316. 560.14 0.225 KA
23 27.440 3.2504 1.3 127. 53.87 0.182 KA
24 28.724 3.1080 0.7 65. 27.69 0.150 KA
25 29.241 3.0542 14.9 1415. 602.46 Oil 90 KA
26 29.523 3.0256 2.6 246. 104.77 0.114 KA
27 30.320 2.9770 0.4 37. 15.82 0.105 KA
28 30.718 2.9106 0.8 78. 33.13 0.114 KA
No. 2Theta d Rel 1 (%) Max 1 inter 1 Width TyDe Range #;1
29 31.000 2.8848 4.1 393. 167.41 0.166 KA
30 31.320 2.8560 22.3 2115. 900.43 0.202 KA
31 31.517 2.8386 9.0 850. 361.88 0.087 KA
32 31.877 2.8074 1.2 112. 47.86 0.093 KA
33 32.161 2.7832 0.9 88. 37.67 0.190 KA
34 32.962 2.7174 1.2 110. 46.95 0.195 KA
35 33.160 2.7016 0.9 83. 35.16 0.130 KA
36 34.564 2.5950 2.1 201. 85.62 0.313 KA
37 35.082 2.5579 1.0 91. 38.64 0.190 KA
38 35.414 2.5347 .04 38. 16.07 0.150 KA
39 36.481 2.4630 .06 58. 24.57 0.289 KA
40 36.880 2.4372 1.8 174. 74.26 0.232 KA
41 37.553 2.3951 0.3 25. 10.72 0.128 KA
42 38.763 2.3231 0.7 68. 28.98 0.186 KA
43 39.684 2.2712 0.6 58. 24.60 0.154 KA
Table 3: infrared study of the monohydrate.
X = Wave Number (cm-1) Y = % Transmittance
Minima list:
X= 401.01 Y= 74.671
X= 412.24 Y= 65.302
X= 423.41 Y= 69.309
X= 472.19 Y= 61.388
X= 514.09 Y= 41.887
X= 524.54 Y= 24.319
X= 575.83 Y= 35.241
X= 585.79 Y= 49.565
X= 616.08 Y= 34.126
X = Wave Number (cm 1) Y = % Transmittance
Minima List: :
X= 652.56 Y= 24.234
X= 674.27 Y= 21.966
X= 691.16 Y= 45.287
X= 710.76 Y= 45.072
X= 733.47 Y= 44.637
X= 768.57 Y= 40.909
X= 803.16 Y= 38.163
X= 830.79 Y= 43.960
X= 846.54 Y= 24.417
X= 861.01 Y= 39.058
X= 869.03 Y= 35.567
X= 888.11 Y= 40.091
X= 911.51 Y= 40.687
X= 960.59 Y= 30.637
X= 967.40 Y= 26.596
X= 999.88 Y= 53.728
X= 1011.6 Y= 35.138
X= 1026.0 Y= 46.938
X= 1075.3 Y= 29.632
X= 1090.5 Y= 34.521
X= 1115.8 Y= 24.541
X= 1137.8 Y= 19.882
X= 1158.7 Y= 58.609
X= 1178.1 Y= 68.849
X= 1203.7 Y= 33.344
X= 1233.2 Y= 56.861
X= 1254.2 Y= 36.911
X= 1272.4 Y= 21.017
X= 1300.6 Y= 43.687
X = Wave Number (cm 1) Y = % Transmittance
Minima Ust:: X= 13174 Y= 50.529
X= 1343.2 Y= 46.875
X= 1353.1 Y= 46.096
X= 1367.3 Y= 45.838
X= 1418.1 Y= 29.272
X= 1452.1 Y= 40.817
X= 1463.6 Y= 45.921
X= 1480.2 Y= 51.373
X= 1502.4 Y= 20.792
X= 1514.5 Y= 25.369
X= 1520.2 Y= 24.828
X= 1598.2 Y= 36.532
X= 1619.8 Y= 31.939
X= 1690.1 Y= 71.970
X= 1733.1 Y= 66.893
X= 1755,8 Y= 71.135
X= 1774.0 Y= 66.912
X= 1916.3 Y= 73.697
Table 4: Infrared study of the anhydrous compound.
X = Wave Number (cm-l) Y = % Transmittance
Minima List:
X= 411.35 Y= 51.675
X= 464.40 Y= 49.164
X= 484.88 Y= 66.633
X= 515.93 Y= 33.593
X= 523.91 Y= 24.889
X= 568.75 3(= 29.813
X = Wave Number (cam'') Y = % Transmittance
Minima List:
X= 586.90 Y= 43.586
X= 609.08 Y= 28.770
X= 646.70 Y= 31.081
X= 658.14 Y= 27.625
X= 680.30 Y= 21.359
X= 701.67 Y= 36.961
X= 739.01 Y= 38.490
X= 761.24 Y= 34.696
X= 793.82 Y= 41.455
X= 817.56 Y= 35.233
X= 851.26 Y= 21.403
X= 884.99 Y= 26.713
X= 896.02 Y= 36.000
X= 909.33 Y= 30.190
X= 928.60 Y= 50.259
X= 966.55 Y= 21.207
X= 1001.9 Y= 42.482
X= 1011.5 Y= 32.103
X= 1017.5 Y= 30.487
X= 1078.8 Y= 24.712
X= 1085.2 Y= 24.896
X= 1104.4 Y= 20.493
X= 1144.5 Y= 19.156
X= 1211.0 Y= 29.764.
X= 1219.6 Y= 31.157
X= 1235.5 Y= 49.883
X= 1260.5 Y= 32.430
X= 1279.2 Y= 17.401
X= 1293.8 Y= 33.097
X = Wave Number (cm-1)
Y = % Transmittance
Minima List:
X= 1316.9 Y= 43.567
X= 1343.5 Y= 32.684
X= 1386.5 Y= 28.788
X= 1420.2 Y= 22.072
X= 1433.2 Y= 32.823
X= 1449.4 Y= 37.313
X= 1507.0 Y= 16.764
X= 1515.5 Y= 21.299
X= 1559.9 Y= 60.459
X= 1601.2 Y= 36.711
X= 1619.6 Y= 22.969
X= 1664.2 Y= 70.951
X= 1698.5 Y= 72.428
X= 1766.0 Y= 60.178
X= 1817.6 Y= 79.273
X= 1844.2 Y= 68.662
X= 1899.1 Y= 71.926
Claims (3)
1. The monohydrate of 2-(2,4-difluorophenyI)-1 ,3-bis(lH-l ,2,4-triazol-1- yl)propan-2-ol.
2. A pharmaceutical composition comprising a pharmaceutically
acceptable carrier and an antifungal amount of a compound as claimed in clairri 1.
3. A method of treating fungal infections in a warm blooded animal, which
comprises administering to said animal an antifungal amount of a compound as
claimed in claim 1.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94269792A | 1992-09-09 | 1992-09-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB9318592D0 GB9318592D0 (en) | 1993-10-27 |
| GB2270521A true GB2270521A (en) | 1994-03-16 |
Family
ID=25478470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9318592A Withdrawn GB2270521A (en) | 1992-09-09 | 1993-09-08 | Crystalline monohydrate of 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2270521A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004524348A (en) * | 2001-03-23 | 2004-08-12 | リチュテル・ゲデオン・ヴェジェーセティ・ジャール・エルテー | Method for producing fluconazole and its crystalline deformation |
| WO2011101862A1 (en) | 2010-02-17 | 2011-08-25 | Fdc Limited | Stabilized fluconazole polymorph iii formulation |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2099818A (en) * | 1981-06-06 | 1982-12-15 | Pfizer Ltd | Triazoles |
-
1993
- 1993-09-08 GB GB9318592A patent/GB2270521A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2099818A (en) * | 1981-06-06 | 1982-12-15 | Pfizer Ltd | Triazoles |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004524348A (en) * | 2001-03-23 | 2004-08-12 | リチュテル・ゲデオン・ヴェジェーセティ・ジャール・エルテー | Method for producing fluconazole and its crystalline deformation |
| US7094904B2 (en) | 2001-03-23 | 2006-08-22 | Richter Gedeon Vegyeszeti Gyar Rt. | Process for preparing monohydrate and crystal modifications of fluconazole |
| WO2011101862A1 (en) | 2010-02-17 | 2011-08-25 | Fdc Limited | Stabilized fluconazole polymorph iii formulation |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9318592D0 (en) | 1993-10-27 |
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