FORM 2
THE PATENTS ACT 1970
(Act 39 of 1970)
PROVISIONAL SPECIFICATION
(SECTION 10, rule 13)

a

AN AMORPHOUS FORM OF FEBUXOSTAT AND PROCESS FOR
ITS PREPARATION"


Enaltec Labs Private Limited
An Indian Company,
Registered under the Indian company's Act 1957
And having its registered office at
B/520, Nand Dham, Sector 11, CBD Belapur,
Navi Mumbai-400 614, INDIA

THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION



FIELD OF THE INVENTION
The present invention relates to an amorphous form of Febuxostat and process for its preparation.
BACKGROUND OF THE INVENTION
Febuxostat, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-l,3-thiazoIe-5-carboxylic acid, has the following structure,

Formula (I)
As described in international publication WO92/09279, it is known that Febuxostat has an activity for inhibiting xanthine oxidase. However, the above mentioned publication does not describe polymorphism.
US patent No.5, 614,520 discloses crystalline form of febuxostat and process for preparation thereof.
Accordingly in case where a plurality of polymorphs is present, it is important to develop a technique of preferentially producing each polymorph. Particularly in case where a pharmaceutical composition comprising a useful compound as a drug is produced, it is suitable to control polymorphism so as to formulate a pharmaceutical composition containing only a superior specific polymorph.
It is known that different polymorphic forms of a same drug may have substantial differences in certain pharmaceutically important properties. The amorphous form of a drug may exhibit different dissolution characteristics and in some case different


bioavailability than its crystalline forms. See e.g. Konne T., Chem Pahrm. Bull.38, 2003 (1990).For some therapeutic indications one bioavailability pattern may be favored over another. For example, the amorphous form of cefuroxin axetil exhibit higher bioavailability than its crystalline form. Further, amorphous and crystalline forms of a drug may have different handling properties, dissolution rates, solubility, and stability. For these reasons, among others, acess to a choice between the amorphous or crystalline forms of a drug is desirable for different applications.Therefor; there is a need for new solid forms of febuxostat and new method for its preparation.
SUMMARY OF THE INVENTION:
In accordance with one aspect, the present invention relates to a novel amorphous form of the antipsychotic drug Febuxostat, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-l, 3-thiazole-5-carboxylic acid.
In accordance with one aspect, the invention provides process for preparing the novel amorphous form of Febuxostat.
In accordance with yet another aspect, the invention provides pharmaceutical compositions containing one or more pharmaceutically acceptable excipients and a prophylactically or therapeutically effective amount of amorphous form of Febuxostat.
BRIEF DESCRIPTION OF THE DRAWING
Figure 1 shows an X-ray diffraction pattern of the amorphous form of Febuxostat prepared by inventors.
DETAILED DESCRIPTION OF THE INVENTION:
It is an object of the present invention to provide febuxostat in a solid amorphous form that affords the compound improved handling properties and improved properties as a pharmaceutical agent.


Therefore, a first aspect of the present invention provides an amorphous form of Febuxostat.
The amorphous form in accordance with the invention can be used to advantage in the preparation of pharmaceutical dosage or drug forms. When in particulate form, the amorphous form in accordance with the invention is free flowing and does not present any of the handling difficulties associated with irregularly shaped crystals. It, therefore, can be employed in the manufacture of pharmaceuticals that do not suffer from the problems, such as inconsistent bioavailability, solubility and dissolution rates, that can be manifest in dosage forms manufactured using previously available forms of febuxostat that have irregularly shaped crystals.
The present invention therefore provides an amorphous form of febuxostat. Preferably the amorphous form of febuxostat is in particulate form. Preferably the amorphous form of febuxostat is substantially pure.
A second aspect of the present invention provides a process for the preparation of an amorphous form of febuxostat, comprising the step of melting one or more crystalline forms of febuxostat. Preferably the process further comprises the step of cooling.
The processes for the preparation of an amorphous form of febuxostat, comprising the step of freeze-drying or spray-drying or forming a solid solution, are particularly suitable for the preparation of amorphous febuxostat on a commercial scale.
In further aspects, the present invention provides a method of preparing a pharmaceutical dosage form that utilizes an amorphous form in accordance with the first aspect of the invention. Preferably the pharmaceutical composition prepared by this method is for oral or parenteral administration. Preferably the pharmaceutical composition is a tablet or capsule for oral administration, or a solution for oral or parenteral administration.
-3JUN2009


The amorphous form in accordance with the invention may also be useful as precursor to other novel polymorphic forms of febuxostat that may be useful in the preparation of pharmaceutical products.
The present invention provides a pharmaceutical composition, comprising an amorphous form of febuxostat. The pharmaceutical composition of the present invention may be for immediate, sustained or delayed release. The amorphous form of febuxostat is particularly suitable for an oral disintegrating formulation.
The present invention is now illustrated, but in no way limited, by the following example and figures.
When exposing X-rays to a sample that is in an ordered crystalline lattice, then a series of diffraction lines is obtained giving a characteristic "finger print" for that lattice. This is the main technique to compare different crystalline polymorphic forms of a compound. However, if the sample is completely in an amorphous state (i. e. not in a regular lattice), then no such diffraction lines will be observed, and a very diffuse broad band will be observed relating to scattering of X-rays from the sample.
Figure 1 shows the XRPD pattern for the sample prepared in Example One and no diffraction is observed, with just a broad diffuse band indicating the sample is in an
amorphous form.
It will be understood that the present invention has been described above by way of example only. The example is not intended to limit the scope of the invention.


Example 1:
crystalline compound 8.0 Gms of febuxostat was weighed into a beaker and placed in to an oven at 215°C to melt. After 45 minutes the molten febuxostat was poured into a dish to form a brittle block. The sample was then allowed to cool at room temperature for 3 hours. The sample was ground in a clay mortar and pestle, and analyzed by XRPD.
£xample2:
Febuxostat (lOgms) was dissolved in methanol (60ml) at 25-30°C. The clear solution was subjected to spray drying in a mini spray dryer at an inlet temperature of 75°C and an outlet temperature of 58°C with a feed rate of 15 ml minute. Febuxostat is an amorphous form was thus isolated.


Claims:
1. An amorphous form of Febuxostat.
2. An amorphous form of febuxostat as claimed in claim 1, wherein the febuxostat is in particulate form.
3. An amorphous form of febuxostat as claimed in 1 or 2 where in the febuxostat is substantially pure.
4. An amorphous of febuxostat as claimed in any one of claims 1 to 3, having XRPD spectrum as shown in figure 1.
5. A process for the preparation of an amorphous form of febuxostat claimed in any one of claims 1 to 4, comprising the step of melting one or more crystalline forms of febuxostat.
6. A process as claimed in claim 5, further comprising the step of cooling the melt.
7. A process for preparing an amorphous form of Febuxostat that comprises for preparing a solution of febuxostat in a suitable solvent of and recovering an amorphous form of febuxostat by preparing the above solution by spray drying.
8. The process of claim 7, where in the suitable solvent is selected from the group consisting of ketones, alcohols, esters, nitriles, chlorinated solvents, ethers or mixtures thereof.
9. The process of claim 8 where in the solvent is preferably selected from the group but not limited to methanol, acetone, ethanol, ethyl acetate, chloroform, dichloro methane, tetra hydro furan, 1,4 -dioxane ,acetonitrile or mixtures thereof and more preferably methanol ,ethanol or mixture thereof.