FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule!3)
1. TITLE OF THE INVENTION:
A PROCESS FOR PREPARATION OF AMORPHOUS FORM OF ARMODAFINIL


2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Limited, D4-MIDC Area, Chikalthana,
Aurangabad - 431 210 (M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a process for the preparation of armodafinil and its pharmaceutical composition in amorphous form.

The following specification particularly describes the invention and the manner in which it is to be performed.


The present invention provides a novel composition of armodafinil with pharmaceutical carrier and their process of preparation in amorphous form of armodafinil.
Armodafinil, Nuvigil is a stimulant like drug of pharmaceutical company Cephalon Inc., Armodafinil is the active (-)-(R)-enantiomer of the racemic drug modafinil (Provigil). It is chemically known as 2-[(R)-diphenylmethyl) sulfinyl] acetamide and represent by formula I.

Armodafinil and its process for preparation are known through U.S. patent No. 4,927,855. Various polymorphic forms are known via US patent No. 7,132,570, and applications 20090018202, US 20060241320 and PCT application WO2008149141.
The invention encompasses amorphous form of armodafinil and process for
preparing of pharmaceutical composition thereof.
The present invention provides the process for the preparation of amorphous armodafinil with pharmaceutical acceptable carrier. The pharmaceutical composition comprises the combination of amorphous armodafinil with a

pharmaceutically acceptable carrier and the processes for preparation of these compositions are provided.
A process for preparation of the pharmaceutical composition amorphous armodafinil with a pharmaceutically acceptable carrier, which comprises removing a solvent from a solution of armodafinil; and a suitable pharmaceutical carrier where one or both are dissolved or dispersed or suspended in an organic solvent.
The present invention provides process for preparation of amorphous armodafinil with pharmaceutically acceptable carrier.
It has observed that these pharmaceutical composition of amorphous armodafinil with pharmaceutically carrier posses strengths over the crystalline forms, i.e. thermodynamic stability, enhanced solubility, and bioavailability.
The process for the preparation of pharmaceutical composition of the amorphous armodafinil includes step of;
a) providing a solution, suspension or dispersion of armodafinil, with pharmaceutical acceptable carrier in an organic solvents,
b) removal of solvent from the solution to providing the desired amorphous armodafinil.
The process for the preparation of pharmaceutical composition comprises the combination of armodafinil with a pharmaceutically acceptable carrier, which comprises removing solvent from a solution of armodafinil and a suitable pharmaceutical carrier, where one or both are dissolved or dispersed or suspended in an organic solvent.
The solution, suspension or dispersion of armodafinil may be prepared by dissolving armodafinil in an organic solvent or it may be obtained directly from a

reaction mixture containing it that is obtained during the course of its manufacture.
The organic solvent may be selected from class of solvents, such as, alcohol , halogenated, hydrocarbons, nitriles, aprotic polar solvents or mixtures thereof.
Non-limiting examples of alcohol includes from the group of C-1 to C-4 straight chain or branched chain alcohol such as methanol, ethanol, n-propanol, isopapanol, t-butanol and the like.
Halogenated solvents are from the group of dichloromethane, 1,2-dichloroethane, chloroform, and carbontetrachloride and hydrocarbons from toluene, xylene, cyclohexane, n-hexane, and n-heptane. Nitrile solvents includes of acetonitrile.
Aprotic polar solvents, such as N,N-dimethylformide (DMF), Dimethylsulfoxide (DMSO), and N,N-dimethylacetamide (DMA) or mixtures thereof.
Suitable pharmaceutically acceptable carriers that may be used in combination with any form of armodafinil include but are not limited to: hydrophilic carriers like polymers of N-vinyl pyrrolidone commonly known as polyvinylpyrrolidine ("PVP" or "povidone"), gums, cellulose derivatives, cyclodextrins, gelatins, hypromellose phthalate, sugars, polyhydric alcohols, polyethylene glycol, polyethylene oxides, polyoxyalkylene derivatives, methacrylic acid copolymers, polyvinyl alcohol, and propylene glycol derivatives.
Useful pyrrolidones are homopolymers or copolymers of N-vinyl pyrrolidone. Such polymers are known to form complexes with a variety of compounds.
The water-soluble forms of N-vinyl pyrrolidone are available in a variety of viscosity and molecular weight grades and may be chosen from but not limited to

PVP K-12, PVP K-15, PVP K-17, PVP K-25, PVP K-30, PVP K-90, PVP K-120 and the like. Pharmaceutically acceptable carriers may be used as such or their mixtures with any of the excipients.
Any pharmaceutical carrier is acceptable as long as it allows the formation of the amorphous armodafinil; it is compatible with the armodafinil and is acceptable for human use.
The dissolution temperature for providing the solution, suspension or dispersion of armodafinil, optionally along with one or more pharmaceutically acceptable carriers may be less than about 130.degree.
The solvent(s) may be removed from the solution, suspension or dispersion by techniques known in art which includes but are not limited to: distillation, evaporation, oven drying, tray drying, spray drying, freeze-drying, fluid bed drying and Ultrafilm agitated thin film dryer-vertical (ATFD-V).
Amorphous armodafinil may be formulated as solid compositions for oral administration in the form of capsules, tablets, pills, powders or granules. In an embodiment of the present invention, the active product in the compositions is mixed with one or more pharmaceutically acceptable excipients. The drug substance may be formulated as liquid compositions for oral administration including for example solutions, suspensions, syrups, elixirs and emulsions, containing solvents or vehicles such as water, sorbitol, glycerine, propylene glycol or liquid paraffin, may be used.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Preparation of Amorphous Armodafinil
EXAMPLE 1
Armodafinil (3.0 gm) and povidone PVK-30 (3.0 gm) were dissolved in methanol (45 mL) at reflux temperature. The clear solution was concentrated at 60 - 65°C at atmospheric pressure. Traces of solvent were removed under reduced pressure to get amorphous product. XRPD Figure-1 Yield: 5.8 gm Melting point 115 °C
EXAMPLE 2 Armodafinil (1 gm) and povidone PVK-30 (1 gm) were dissolved in methanol (15 ml). The clear solution was concentrated at 60 - 65°C at atmospheric pressure. Traces of solvent were removed under reduced pressure to get amorphous product. XRPD Figure-2 Yield: 1.8 gm
EXAMPLE 3 Armodafinil (1.0 gm) and povidone PVK-30 (0.1 gm) were dissolved in 15ml methanol. The solution of armodafinil was filtered to remove undissolved particles. The solution was concentrated at 25-30°C under reduced pressure to get amorphous product. XRPD Figure-3 Yield: 1.0 gm
EXAMPLE 4 Armodafinil (4.5 gm) and povidone PVK-30 (0.5 gm) were dissolved in ethanol (75 mL). The solution was concentrated at 85 - 90 °C at atmospheric pressure to yield a syrupy product. Finally Vacuum was applied to get amorphous product. Yield: 4.8 gm
EXAMPLE 5 Armodafinil (10 gm) was dissolved in ethanol (400 ml) and solution was subjected to spray drying in a Buchi B-190 to get amorphous product. Yield 5.3 gm.

WE CLAIM:
1. A process for the preparation of pharmaceutical composition comprising the
amorphous armodafinil, wherein the said process comprises
a) providing a solution, suspension or dispersion of armodafinil, with pharmaceutical acceptable carrier in an organic solvents,
b) removal of solvent from the solution to providing the desired amorphous armodafinil.

2. The process of claim 1 wherein, the organic solvent are alcoholic solvents, halogenated solvents, hydrocarbons, nitrites, aprotic polar solvents or mixtures thereof.
3. The process of claim 2 wherein, alcoholic solvent are methanol, ethanol, n-propanol, isopapanol and t-butanol.
4. The process of claim 1 wherein, the solvent is removed by distillation, evaporation, oven drying, tray drying, rotational drying, spray drying, freeze-drying, fluid bed drying, flash drying, spin flash drying or thin film drying.
5. The process of claim 3 wherein, solvent removal is performed at temperature below 130°C.
6. The process of claim 1 wherein, pharmaceutical acceptable carrier are from the group of N-vinyl pyrrolidone, gums, cellulose derivatives, cyclodextrins, gelatins, hypromellose phthalate, sugars, polyhydric alcohols, polyethylene glycol, polyethylene oxides, polyoxyalkylene derivatives, methacrylic acid copolymers, polyvinyl alcohol, and propylene glycol or mixture therof.
7. The process of claim 6 wherein, pharmaceutical acceptable carrier is N-vinyl pyrrolidone.

8. A pharmaceutical composition comprising armodafinil, along with pharmaceuticaly acceptable excipients wherein the said composition comprises amorphous form of armodafinil.
9. The pharmaceutical composition of claim 8 wherein, armodafinil composition shows amorphous nature with XRPD.
10. A pharmaceutical composition comprising armodafinil and process for preparing, according to claim 1 to 8, wherein the dosage form is oral solid dosage composition.