FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:
PHARMACEUTICAL DOSAGE FORM COMPRISING TAMSULOSIN OR SALT 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 pharmaceutical dosage form for oral administration comprising tamsulosin or salt thereof along with pharmaceutically acceptable carriers.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention provides pharmaceutical dosage form for oral administration comprising tamsulosin or salt thereof along with pharmaceutically acceptable carriers.
Tamsulosin hydrochloride is an antagonist of alphas adrenoceptors in the prostate. Tamsulosin HCI is (-)-(R)-5-[2-[[2-(o-Ethoxyphenoxy) ethyl] amino] propyl]-2-methoxybenzenesulfonamide, monohydrochloride of formula 1. Tamsulosin HCI is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). It is not indicated for the treatment of hypertension. (R)-tamsulosin hydrochloride is marketed under various trade names, including FLOMAX (Boehringer Ingelheim) in the U.S., HARNAL (Yamanouchi) in Japan and OMNIC (Yamanouchi) in Europe, for treatment of symptoms of benign prostatic hyperplasia (also known as BPH) such as urinary volume and frequency problems. The approved drug products include a capsule dosage form for oral administration that comprises 0.4 mg of the tamsulosin hydrochloride. The capsule provides controlled release of the tamsulosin and is a once daily dosage form, although two capsules can be used if needed; i.e. a maximum single daily administration of 0.8 mg.



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FORMULA 1
U.S. Pat. No. 4,772,475 (EP 194838, EP 533297) discloses controlled-release pharmaceutical dosage forms comprising multiple granulate units containing
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tamsulosin, microcrystalline cellulose and a release control agent. The granulate gradually releases tamsulosin from the granulate matrix. The patent suggests that an enteric coating is not needed.
U. S. Application No. 20050100606 discloses a controlled-release formulation of tamsulosin hydrochloride, which comprises a granular core; and a drug-coating layer coated on the granular core.
U.S. Pat. No. 6,328,979 discloses a sustained-release composition which includes an ionic drug such as tamsulosin hydrochloride and an ionic substance having an opposite charge to that of the ionic drug for increasing hydrophobicity of the ionic drug.
European Patent Application EP 1596849 A1 discloses a controlled release pharmaceutical composition of tamsulosin comprising a spheroid core, one or more of rate controlling polymers, and an enteric coating over the spheroid core, process for preparation of the pharmaceutical composition and method of treating symptoms of benign prostatic hyperplasia comprising administering a controlled-release pharmaceutical composition of tamsulosin.
U. S. Application No. 20050106253 discloses a pharmaceutical dosage form comprising a plurality of pellets, wherein each pellet comprises: a. a pellet core having a diameter within the range of 0.1 to 1.5 mm and comprising tamsulosin or a pharmaceutically acceptable salt thereof, an inert pellet forming carrier, a release control agent and optionally water; and b. an outer layer coat surrounding said core which comprises a pharmaceutically acceptable acid-resistant polymer, wherein the mass of said outer layer coat, calculated on a dry pellet core basis, is within the range of 1-25%; and wherein the plurality of pellets exhibits a dissolution release profile in simulated gastric fluid using Ph. Eur. basket method at 100 rpm which includes releasing less than 25% of the tamsulosin or salt thereof during the first two hours along with process for preparation of the same.
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The present invention now provides a pharmaceutical dosage form for oral administration comprising tamsulosin or salt thereof wherein the dosage form is present in the form of core having a diameter within the range of 2.0mm to 4.0mm and an outer enteric coating surrounding the core.
In one of the aspects of the present invention there is provided a pharmaceutical dosage form for oral administration comprising tamsulosin or salt thereof wherein a dosage form comprises;
a. a core having diameter within the range of 2.0 mm to 4.0mm along with
pharmaceutically acceptable ingredients; and
b. an outer layer enteric coat surrounding the core, wherein the said dosage form
is present with or without an intermediate layer or seal coat in between the core
and the enteric coat.
Tamsulosin can be present in the form of tamsulosin hydrochloride. The dosage form can be selected from tablets, capsules, pellets, caplets, and microtablets. The intermediate layer also can be called as seal coat is formed from an inert water-soluble film former. The pharmaceutically acceptable seal coat forming polymers can be selected from a group comprising of one or more of suitable cellulose ethers and include one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose and other suitable cellulose ethers. The film former has been applied from a solution. The intermediate layer is surrounded by outer enteric coat. The pharmaceutically acceptable enteric coat forming polymers can be selected from methacrylic acid/methyl methacrylate copolymers such as Eudragit L or cellulose derivatives such as carboxymethyl cellulose, cellulose acetate phthalate, hydroxypropylmethyli cellulose phthalate and other suitable polymers.
Pharmaceutically acceptable excipients can be binders, diluents, plasticizers, anti-caking agents, fillers, solubilizing agents, disintegrants, surfactants,
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flavorants, sweeteners, stabilizers, anti-oxidants, anti-adherents, preservatives, glidants and pigments.
Preferred fillers include, but are not limited to, microcrystalline cellulose, starch, dibasic calcium phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, calcium carbonate, dextrose, sucrose, lactose, mannitol, sorbitol and the like.
Preferred binders include, but are not limited to, starches, e.g., potato starch, wheat starch and corn starch; gums, such as gum tragacanth, acacia gum and gelatin; polyvinyl pyrrolidone, purified water and the like.
The lubricant is preferably selected from calcium stearate, magnesium stearate, sodium stearate, zinc stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, polyethylene glycol, sodium benzoate, stearic acid and talc. A combination of lubricants may also be used.
Preferred plasticizers include, but are not limited to, citric and tartaric acid esters such as acetyl-triethyl citrate, acetyl tributyl citrate; glycerol and glycerol esters; phthalic acid esters and the like. A combination of plasticizers may also be used.
Preferred sweeteners include, but are not limited to, artificial sweeteners, such as aspartame, saccharin and cyclamates; natural sweeteners, such as sucrose, fructose, glucose, lactose, maltodextrin and sodium glycolate; and mixtures of artificial and natural sweeteners, such as a mixture of aspartame and sucrose.
Preferred flavorants include, but are not limited to, cherry, strawberry, fruit punch, grape, cream, vanilla, chocolate, mocha, spearmint, cola and the like.
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Preferred pigments include, but are not limited to, titanium dioxide, iron oxide and vegetable dyes.
The dosage form can be prepared by dry granulation, wet granulation or by direct compression. The preferred dosage form is microtablet. The microtablets may be prepared by wet granulation method. Aqueous solution of tamsulosin hydrochloride was prepared and this solution was layered on microcrystalline cellulose followed by granulating the blend with Eudragit L 30 D 55. Granules were dried and lubricated with magnesium stearate. These granules were compressed into microtablets using multi-tip punches. Further the microtablets were coated using enteric coating solution.
The process of coating may be performed in any suitable equipment such as, in a fluid bed coater, or preferably on a coating pan employing polymer solutions in water or in suitable organic solvents or using latex dispersions of these polymers. The results of the coating procedure may be routinely checked by withdrawing sample of the microtablets. Coating was applied till approximately 3% weight gain was achieved.
The microtablets are enclosed inside a capsule, for example, a gelatin capsule. For this any capsule conventionally employed in the pharmaceutical formulation field can 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.
EXAMPLE
Composition of batches is provided in Table 1.
Table 1 - Tamsulosin hydrochloride 0.4mg enteric-coated micro tablets
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Sr. No. Ingredient Mg/capsule % w/w
CORE
1 Tamsulosin hydrochloride 0.4 0.17
2 Microcrystalline cellulose (Avicel pH 101) 146.9 63.37
3 Magnesium stearate 5.7 2.45
4 Eudragit L 30 D 55 250ml=75 32.25
5 Purified water q.s. -
Total Weight (mg) 228
ENTERIC COAT
1 Eudragit L 30 D 55 20ml=6 2.58
2 Tri ethyl citrate 0.3 0.12
3 Talc 0.48 0.20
4 Purified water q.s. -
Total Fil Weight (mg) 231.78 -
Procedure -
a) Preparation of core-
1) Tamsulosin hydrochloride was dissolved in purified water.
2) Microcrystalline cellulose was sifted through # 60.
3) Drug layering was carried out over microcrystalline cellulose using tamsulosin hydrochloride solution.
4) This blend was dried, sifted and further granulated with Eudragit L 30 D 55.
5) Granules were dried at 60°C and lubricated with 60 # passed magnesium stearate.
6) This blend was further compressed into microtablets using multi-tip punches of desired shape and size.
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b) Enteric coating-
1) Eudragit L 30 D 55 was diluted with purified water.
2) Tri ethyl citrate and talc was further added to this solution.
3) Coating was applied till the desired weight gain is achieved.
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WE CLAIM:
1) A pharmaceutical dosage form for oral administration comprising tamsulosin or
salt thereof wherein a dosage form comprises;
a. a core having diameter within the range of 2.0 mm to 4.0mm along with
pharmaceutically acceptable ingredients; and
b. an outer layer enteric coat surrounding the core, wherein the said dosage form
is present with or without an intermediate layer or seal coat in between the core
and the enteric coat.
2) The dosage form according to claim 1, wherein the tamsulosin is a salt selected from the group consisting of tamsulosin hydrochloride, hydrobromide, sulfate, phosphate, acetate, propionate, maleate, fumarate, malonate, lactate, citrate, tartrate, mesylate, and besylate.
3) The dosage form according to claim 2, wherein the tamsulosin salt is tamsulosin hydrochloride.
4) The dosage form according to claim 1, wherein the enteric coating comprises a pharmaceutically acceptable polymer.
5) The dosage form according to claim 4, wherein the pharmaceutically
acceptable polymer is selected from the group consisting of acrylic polymers,
cellulose derivatives, and combinations thereof.
6) The dosage form according to claim 1, wherein oral dosage form is tablet, capsule, granule, microtablet or pellet.
7) The dosage form according to claim 1, wherein the excipient is selected from the group consisting of binders, diluents, fillers, plasticizers, enteric coating agents, lubricants, glidants and the like.
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8) A dosage form according to claim 1, wherein lubricant may be one or more of magnesium stearate, calcium stearate, polyethylene glycol, hydrogenated vegetable oils, stearic acid, sodium stearyl fumarate and sodium benzoate.
9) A dosage form according to claim 1, wherein the lubricant is magnesium stearate.

Dated this 28th day of June, 2006 For Wockhardt Limited
(Yatendra Kumar) Authorized Signatory
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