FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
PHARMACEUTICAL COMPOSITION OF MODAFINIL OR SALTS THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra
(East), Mumbai-400 051.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a pharmaceutical composition of modafinil or pharmaceutically acceptable salts thereof comprising a mixture of micronized and unmicronized modafinil particles, sodium starch glycolate and one or more pharmaceutically acceptable excipients.
The following specification particularly describes the invention and the manner in which it is to be performed.
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4. Description
The present invention provides a pharmaceutical composition of modafinil or pharmaceutical^ acceptable salts thereof comprising a mixture of micronized and unmicronized modafinil particles, sodium starch glycolate and one or more pharmaceutically acceptable excipients.
Modafinil is a wakefulness-promoting agent indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. It has molecular weight of 273.36. The chemical name of modafinil is (2-[(diphenylmethyl) sulfinyl] acetamide. Its empirical formula is C15H15NO2S, and its structural formula is:


o o
II II
CH—S-CH2—C-NH2

U.S. Patent No 4,927,855 discloses the levorotatory form of modafinil and the use of the levorotatory form for treating hypersomnia and Alzheimer's disease
U.S. Patent No 4,177,290 relates to modafinil drug used for the treatment of idiopathic hypersomnia and narcolepsy.
U.S. Patent No RE 37,516 provides a method of size reduction and a pharmaceutical composition that has at least 95% of the modafinil particles having a diameter of less than 200 mu.m.
U.S. Patent No 6,919,378 describes solid dispersion of modafinil.
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U.S. Patent No 6,489,363 relates to pharmaceutical compositions comprising a modafinil compound in solution, and in particular, to non-aqueous solutions comprising at least one organic solvent
U.S. Patent No. 7,115,281 relates to processes for preparing, and pharmaceutical compositions of, modafinil dosage forms for oral administration. The dosage forms include a mixture of coarse and fine particles of modafinil.
U.S. Patent No. 7,141,555 relates to complexes of a modafinil compound with a cyclodextrin.
U.S. Published Application Nos. 20030022940, 2003220403, 20040105891, 20050137264, 20040170683, 20040048931, 20070026507 describes pharmaceutical compositions of modafinil.
U.S. Published Application No 20040253308 relates to solid oral dosage form comprising surface-treated particles of modafinil.
U.S. Published Application No 2004116532 describes pharmaceutical unit dose of modafinil and method of treating ADHD by using modafinil.
U.S. Published Application No 2006024370 describes oral lyophilizate of modafinil.
U.S. Published Application No 20070065517 describes method of formulating a composition of modafinil.
International (PCT) Publication WO2007013962 describes pharmaceutical composition of modafinil comprising combination of d and l-enantiomers of modafinil and modafinil component is greater than 50% by weight d-modafinil.
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The present inventors while working on the modafinil formulation have noticed that when modafinil composition is formulated using sodium starch glycolate alongwith pharmaceutically acceptable excipients the resulting formulation exhibits desired therapeutic effect, possess no stability problems and modulated release. The modafinil in the composition of the present invention is present as a mixture of micronized and unmicronized particles.
One of the aspects of the present invention provides a pharmaceutical composition of modafinil or pharmaceutically acceptable salts thereof comprising mixture of micronized and unmicronized modafinil particles, sodium starch glycolate, in admixture with one or more pharmaceutically acceptable excipients.
As used herein, "micronized" means modafinil is subjected to micronisation methods. The micronisation methods include conventional micronization equipment such as air jet milling and also include methods that are known to ordinary skilled in the art.
The micronized modafinil particles contain atleast about 90% of the particles having particle size less than 50μm and atleast about 50% of the particles having particle size less than 25μm. As used herein, "about" means plus or minus approximately ten percent of the indicated value, such that "about 90%" indicates approximately 81% to 99%.
As used herein, "unmicronized" means modafinil is not subjected to micronisation. The unmicronized modafinil particles contain atleast about 90% of the particles having particle size more than 250μm.
The "mixture of micronized and unmicronized modafinil particles" means the mixture contains both micronized and unmicronized modafinil particles and the ratio of micronized to unmicronized modafinil particles ranges from 1:0.1 to 1:100.
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The pharmaceutical composition comprises of pharmaceutically acceptable excipients wherein excipients comprise one or more of binders, fillers, lubricants, and glidants.
Suitable binders comprise one or more of, povidone, starch, stearic acid, gums, hydroxypropylmethyl cellulose and the like. Suitable fillers comprise one or more of microcrystalline cellulose, lactose, mannitol, calcium phosphate, calcium sulfate, kaolin, dry starch, powdered sugar and the like. Suitable lubricants comprise one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oil and the like. Suitable glidants comprise one or more of colloidal silicon dioxide, talc or cornstarch and the like.
The pharmaceutical composition of the present invention include but not limited to one or more of tablet, capsule, powder, sachet, pills, granule and the like and is meant for oral administration.
In yet another aspect of the present invention there is provided a process for preparing a pharmaceutical composition of modafinil or pharmaceutically acceptable salts thereof comprising the steps of:
a) blending mixture of micronized and unmicronized modafinil particles, sodium starch glycolate and optionally one or more pharmaceutically acceptable excipients
b) granulating the blend of step a)
In the process of the present invention blending of mixture of micronized and unmicronized modafinil particles, sodium starch glycolate and optionally one or more pharmaceutically acceptable excipients can be done by methods known to ordinary skilled in the art.
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In the process of the present invention granulation can be done by dry granulation or wet granulation. The composition of the present invention can also be prepared by direct compression method.
The pharmaceutical composition can be prepared by dry granulation, wet granulation or direct compression method.
The composition of the present invention can be prepared by blending mixture of micronized and unmicronized modafinil particles, sodium starch glycolate and suitable filler. The blend is granulated using a suitable binder solution. Mixing dried granules with suitable glidant followed by lubricating it with suitable lubricant. Compressing lubricated granules to form a tablet.
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.
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EXAMPLE 1
Table 1: Composition of modafinil tablets

No Ingredients % Composition
1. Modafinil (Micronised) 26
2. Modafinil (Unmicronised) 14
3. Lactose Monohydrate 15
4. Microcrystalline cellulose 36.5
5. Sodium Starch Glycolate 4
6. PVP K-30 3
7. Colloidal Silicon dioxide 0.5
8. Magnesium Stearate 1
Total 100
Procedure: The composition is prepared by blending micronized modafinil particles, unmicronized modafinil particles, Lactose Monohydrate, Microcrystalline cellulose and sodium starch glycolate. The obtained blend is granulated using PVP K-30 solution. Modafinil granules are dried and mixed with Colloidal Silicon dioxide followed by lubricating it with Magnesium Stearate. The lubricated modafinil granules are compressed using suitable tooling to form to form a tablet.
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WE CLAIM:
1. A pharmaceutical composition of modafinil or pharmaceutical^ acceptable salts thereof comprising mixture of micronized and unmicronized modafinil particles, sodium starch glycolate in admixture with one or more pharmaceutically acceptable excipients.
2. A process for preparing a pharmaceutical composition of modafinil or pharmaceutically acceptable salts thereof comprising the steps of:

a) blending mixture of micronized and unmicronized modafinil particles, sodium starch glycolate and optionally one or more pharmaceutically acceptable excipients
b) granulating the blend of step a)

3. A pharmaceutical composition of claim 1 and a process of claim 2, wherein ratio of micronized to unmicronized modafinil particles ranges from 1:0.1 to 1:100.
4. A pharmaceutical composition of claim 1 is meant for oral administration.
5. A pharmaceutical composition of claim 1 comprises one or more of a tablet, capsules, powder, disc, caplet, granules, pellets, sachets.
6. A pharmaceutical composition of claim 1 and a process of claim 2, wherein pharmaceutically acceptable excipients comprise one or more of binders, fillers, lubricants and glidants.
7. A pharmaceutical composition and a process of claim 6 wherein binders comprise one or more of povidone, starch, stearic acid, gums, hydroxypropylmethyl cellulose.
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8. A pharmaceutical composition and a process of claim 6 wherein fillers comprise one or more of microcrystalline cellulose, lactose, mannitol, calcium phosphate, calcium sulfate, kaolin, dry starch, powdered sugar.
9. A pharmaceutical composition and a process of claim 6 wherein lubricants comprise one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oil.
10. A pharmaceutical composition and a process of claim 6 wherein glidants comprise one or more of colloidal silicon dioxide, talc or cornstarch.
Dated this 27TH day of April, 2007 For Wockhardt Limited

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