Sustained release pharmaceutical composition

1. A sustained-release pharmaceutical composition, which contains tamsulosin or a pharmaceutically acceptable salt thereof and a carrier for a sustained-release pharmaceutical composition, when a test is carried out according to Japanese Pharmacopoeia Dissolution Test Method 2 (paddle method: 200 rpm), tamsulosin release after 7 hours from the start of the dissolution is about 20% to about 85%, wherein said carrier is a member selected from the group consisting of (B) a preparation of an osmotic pump formulation comprising a two-layered compressed core containing tamsulosin or a pharmaceutically acceptable salt thereof containing a poly(alkylene oxide) polymer with a number average molecular weight of 100,000 to 750,000 and a push layer containing a poly(alkylene oxide) polymer with a number average molecular weight of 1,000,000 to 15,000,000 coated with a semipermeable membrane containing a member selected from the group consisting of a cellulose ester, a cellulose ether and a cellulose ester-ether; (C) a gel preparation in which a plurality of gums are combined comprising a hetero polysaccharide gum selected from the group consisting of xanthan gum and a xanthan gum derivative selected from a deacylated xanthan gum, a carboxymethyl ether and propylene glycol ester and a homo polysaccharide gum, which is locust bean, a water-soluble cationic cross-linking agent, an inert diluent, and ethyl cellulose; (D) a multi-layered tablet preparation comprising 3 layers,

i) a first layer comprising a mixture or granules containing 5 to 90 w/w % of a water-soluble polymer in the first layer and having a property of being swollen by contact to environmental fluids and ethyl cellulose;

ii) a second layer comprising a water-soluble polymer of hydroxymethylcellulose, auxiliary substances of microcrystalline cellulose and polyvinylpyrrolidone and containing tamsulosin or a pharmaceutically acceptable salt thereof which is adjacent to the first layer and;

iii) a third layer being adhered to the second layer which comprises ethyl cellulose and a water-soluble polymer which is gelled and/or swollen followed by free disintegration, wherein said water-soluble polymer in the first, second and third layers can be the same or different and is a member selected from the group consisting of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl cellulose;

wherein when said composition selected from the group consisting of B, C, and D is administered before ingestion of food or after ingestion of food, there is no significant difference of C max obtained from plasma tamsulosin concentrations.

2. The sustained-release pharmaceutical composition according to claim 1 , wherein the tamsulosin release after 7 hours from the start of the dissolution is about 20 to about 75%.

3. The sustained-release pharmaceutical composition according to claim 1 , wherein the tamsulosin release after 7 hours from the start of the dissolution is about 25 to about 65%.

4. A sustained-release pharmaceutical composition, which contains tamsulosin or a pharmaceutically acceptable salt thereof and a carrier for a sustained-release pharmaceutical composition, when a test is carried out according to Japanese Pharmacopoeia Dissolution Test Method 2 (paddle method: 200 rpm), tamsulosin release after 3 hours from the start of the dissolution is about 5 to about 45% wherein said carrier is a member selected from the group consisting of

(B) a preparation of an osmotic pump formulation comprising a two-layered compressed core containing tamsulosin or a pharmaceutically acceptable salt thereof containing a poly(alkylene oxide) polymer with a number average molecular weight of 100,000 to 750,000 and a push layer containing a poly(alkylene oxide) polymer with a number average molecular weight of 1,000,000 to 15,000,000 coated with a semipermeable membrane containing a member selected from the group consisting of a cellulose ester, a cellulose ether and a cellulose ester-ether; (C) a gel preparation in which a plurality of gums are combined comprising a hetero polysaccharide gum selected from the group consisting of xanthan gum and a xanthan gum derivative selected from a deacylated xanthan gum, a carboxymethyl ether and propylene glycol ester and a homo polysaccharide gum, which is locust bean, a water-soluble cationic cross-linking agent, an inert diluent, and ethyl cellulose; (D) a multi-layered tablet preparation comprising 3 layers,

i) a first layer comprising a mixture or granules containing 5 to 90 w/w % of a water-soluble polymer in the first layer and having a property of being swollen by contact to environmental fluids and ethyl cellulose;

ii) a second layer comprising a water-soluble polymer of hydroxymethylcellulose, auxiliary substances of microcrystalline cellulose and polyvinylpyrrolidone and containing tamsulosin or a pharmaceutically acceptable salt thereof which is adjacent to the first layer and,

iii) a third layer being adhered to the second layer which comprises ethyl cellulose and a water-soluble polymer which is gelled and/or swollen followed by free disintegration, wherein said water-soluble polymer in the first, second and third layers can be the same or different and is a member selected from the group consisting of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl cellulose;

and wherein when said composition selected from the group consisting of B, C, and D is administered before ingestion of food or after ingestion of food, there is no significant difference of C max obtained from plasma tamsulosin concentrations.

5. The sustained-release pharmaceutical composition according to claim 4 , wherein the tamsulosin release after 3 hours from the start of the dissolution is about 5 to about 40%.

6. The sustained-release pharmaceutical composition according to claim 4 , wherein the tamsulosin release after 3 hours from the start of the dissolution is about 5 to about 35%.

7. The sustained-release pharmaceutical composition according to claim 1 , wherein the tamsulosin release after 12 hours from the start of the dissolution is about 40% or more.

8. The sustained-release pharmaceutical composition according to claim 1 , wherein the tamsulosin release after 12 hours from the start of the dissolution is about 50% or more.

9. The sustained-release pharmaceutical composition according to claim 1 , wherein the time during which 50% of tamsulosin has been released (T50) is about 3 hours to about 15 hours.

10. The sustained-release pharmaceutical composition according to claim 1 , wherein T50 ranges from about 4 hours to about 12 hours.

11. The sustained-release pharmaceutical composition according to claim 1 , wherein its adverse event profile is not significantly different as compared with placebo.

12. The sustained-release pharmaceutical composition according to claim 1 , wherein it is a preparation of an osmotic pump comprising a two-layered compressed core containing tamsulosin or a pharmaceutically acceptable salt thereof containing a poly(alkylene oxide) polymer with a number average molecular weight of 100,000 to 750,000 and a push layer containing a poly(alkylene oxide) polymer with a number average molecular weight of 1,000,000 to 15,000,000 coated with a semipermeable membrane containing a member selected from the group consisting of a cellulose ester, a cellulose ether and a cellulose ester-ether.

13. The sustained-release pharmaceutical composition according to claim 1 , wherein it is said gel preparation where a plurality of gums is combined comprising a hetero polysaccharide gum selected from the group consisting of xanthan gum and a xanthan gum derivative selected from a deacylated xanthan gum, a carboxymethyl ether and propylene glycol ester and a homo polysaccharide gum, which is locust bean, a water-soluble cationic cross-linking agent, an inert diluent, and ethyl cellulose.

14. The sustained-release pharmaceutical composition according to claim 1 , wherein said composition is a multi-layered tablet comprising 3 layers,

i) a first layer comprising a mixture or granules containing 5 to 90 w/w % of a water-soluble polymer in the first layer and having a property of being swollen by contact to environmental fluids and ethyl cellulose;

ii) a second layer comprising a water-soluble polymer of hydroxymethylcellulose, auxiliary substances of microcrystalline cellulose and polyvinylpyrrolidone and containing tamsulosin or a pharmaceutically acceptable salt thereof which is adjacent to the first layer and;

iii) a third layer being adhered to the second layer which comprises ethyl cellulose and a water-soluble polymer which is gelled and/or swollen followed by free disintegration, wherein said water-soluble polymer in the first, second and third layers can be the same or different and is a member selected from the group consisting of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl cellulose.

15. A method for administering tamsulosin or a pharmaceutically acceptable salt thereof, which reduces adverse reactions, said method comprising:

administering a sustained-release pharmaceutical composition which contains tamsulosin or a pharmaceutically acceptable salt thereof, wherein said carrier is a member selected from the group consisting of (B) a preparation of an osmotic pump formulation comprising a two-layered compressed core containing tamsulosin or a pharmaceutically acceptable salt thereof containing a poly(alkylene oxide) polymer with a number average molecular weight of 100,000 to 750,000 and a push layer containing a poly(alkylene oxide) polymer with a number average molecular weight of 1,000,000 to 15,000,000 coated with a semipermeable membrane containing a member selected from the group consisting of a cellulose ester, a cellulose ether and a cellulose ester-ether; (C) a gel preparation in which a plurality of gums are combined comprising a hetero polysaccharide gum selected from the group consisting of xanthan gum and a xanthan gum derivative selected from a deacylated xanthan gum, a carboxymethyl ether and propylene glycol ester and a homo polysaccharide gum, which is locust bean, a water-soluble cationic cross-linking agent, an inert diluent, and ethyl cellulose; (D) a multi-layered tablet preparation comprising 3 layers,

i) a first layer comprising a mixture or granules containing 5 to 90 w/w % of a water-soluble polymer in the first layer and having a property of being swollen by contact to environmental fluids and ethyl cellulose;

ii) a second layer comprising a water-soluble polymer of hydroxymethylcellulose, auxiliary substances of microcrystalline cellulose and polyvinylpyrrolidone and containing tamsulosin or a pharmaceutically acceptable salt thereof which is adjacent to the first layer and;

iii) a third layer being adhered to the second layer which comprises ethyl cellulose and a water-soluble polymer which is gelled and/or swollen followed by free disintegration, wherein said water-soluble polymer in the first, second and third layers can be the same or different and is a member selected from the group consisting of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl cellulose; and

wherein when said composition selected from the group consisting of B, C, and D; when an in vitro test is carried out according to Japanese Pharmacopoeia Dissolution Test Method 2 (paddle method: 200 rpm), tamsulosin release after 7 hours from the start of the dissolution is about 20% to about 85%, with said pharmaceutical composition; thereby reducing adverse reactions.

16. The method according to claim 15 , wherein it is a preparation of an osmotic pump comprising a two-layered compressed core containing tamsulosin or a pharmaceutically acceptable salt thereof containing a poly(alkylene oxide) polymer with a number average molecular weight of 100,000 to 750,000 and a push layer containing a poly(alkylene oxide) polymer with a number average molecular weight of 1,000,000 to 15,000,000 coated with a semipermeable membrane containing a member selected from the group consisting of a cellulose ester, a cellulose ether and a cellulose ester-ether.

17. The method according to claim 15 , wherein it is a gel preparation where said plurality of gums is combined comprising a hetero polysaccharide gum selected from the group consisting of xanthan gum and a xanthan gum derivative selected from a deacylated xanthan gum, a carboxymethyl ether and propylene glycol ester and a homo polysaccharide gum, which is locust bean, a water-soluble cationic cross-linking agent, an inert diluent, and ethyl cellulose.

18. The method according to claim 15 , wherein said composition is a multi-layered tablet comprising 3 layers,

i) a first layer comprising a mixture or granules containing 5 to 90 w/w % of a water-soluble polymer in the first layer and having a property of being swollen by contact to environmental fluids and ethyl cellulose;

ii) a second layer comprising a water-soluble polymer of hydroxymethylcellulose, auxiliary substances of microcrystalline cellulose and polyvinylpyrrolidone and containing tamsulosin or a pharmaceutically acceptable salt thereof which is adjacent to the first layer and;

iii) a third layer being adhered to the second layer which comprises ethyl cellulose and a water-soluble polymer which is gelled and/or swollen followed by free disintegration, wherein said water-soluble polymer in the first, second and third layers can be the same or different and is a member selected from the group consisting of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl cellulose.