Claims for Patent: 6,884,433

Summary for Patent: 6,884,433

Title:	Sustained release formulation containing tacrolimus
Abstract:	Sustained release formulation containing tacrolimus or its hydrate is provided. The time (T63.2%) required for 63.2% of the maximum amount of tacrolimus or its hydrate to be dissolved is 0.7 to 15 hours. The time is measured in accordance to the Japanes Pharmacopocia, the 13-th edition, Dissolution Test, No. 2 (Puddles method, 50 rpm) using an aqueous 0.005% hydroxypropyl cellulose solution. This aqueous test solution is adjusted to pH 4.5, accordingly. The formulation further comprises a solid base which is a water-soluble or water-insoluble polymer. The formulation is in the form of a powder, fine powder, granule, tablet or capsule. The formulation is administered to a patient once a day for preventing organ or tissue rejection by transplantation or autoimmune disease. In addition, a solid dispersion composition is provided. The solid dispersion comprises tacrolimus or its hydrate in a mixture containing water-soluble or water-insoluble polymer and an excipient.
Inventor(s):	Yamashita; Kazunari (Kyoto, JP), Hashimoto; Eiji (Wakayama, JP), Nomura; Yukihiro (Osaka, JP), Shimojo; Fumio (Hyogo, JP), Tamura; Shigeki (Osaka, JP), Hirose; Takeo (Kyoto, JP), Ueda; Satoshi (Hyogo, JP), Saitoh; Takashi (Osaka, JP), Ibuki; Rinta (Kyoto, JP), Ideno; Toshio (Osaka, JP)
Assignee:	Fujisawa Pharmaceutical Co., Ltd. (Osaka, JP)
Application Number:	10/412,281
Patent Claims:	1. A sustained-release formulation comprising a solid dispersion composition, wherein the solid dispersion composition comprises tacrolimus or its hydrate, in a mixture comprising a water-soluble polymer and a water-insoluble polymer, and an excipient. 2. The sustained-release formulation of claim 1, wherein the solid dispersion composition has a particle size equal to or smaller than 250 .mu.m. 3. The sustained-release formulation of claim 1, wherein the weight ratio of the water-soluble polymer to tacrolimus is 0.2-0.4:1, and the weight ratio of the water-insoluble polymer to tacrolimus is 0.1-5:1. 4. The sustained-release formulation of claim 3, wherein the weight ratio of the water-insoluble polymer to tacrolimus is 0.1-1:1. 5. The sustained-release formulation of claim 1, wherein the water-insoluble polymer is ethylcellulose. 6. The sustained-release formulation of claim 1 wherein the water-soluble polymer is hydroxypropylmethyl cellulose. 7. The sustained-release formulation of claim 1, wherein the excipient is lactose. 8. The sustained-release formulation of claim 7, wherein the weight ratio of lactose to tacrolimus is 2, 3 or 5:1. 9. The sustained-release formulation of claim 1, wherein the solid dispersion composition does not substantially contain any disintegrators. 10. The sustained-release formulation of claim 1, wherein tacrolimus or its hydrate is present as an amorphous state. 11. The sustained-release formulation of claim 2, wherein the weight ratio of the water-soluble polymer to tacrolimus is 0.2-0.4:1, and the weight ratio of the water-insoluble polymer to tacrolimus is 0.1-5:1. 12. The sustained-release formulation of claim 11, wherein the weight ratio of the water-insoluble polymer to tacrolimus is 0.1-1:1. 13. The sustained-release formulation of claim 6, wherein the water-insoluble polymer is ethylcellulose. 14. The sustained-release formulation of claim 13, wherein the excipient is lactose. 15. The sustained-release formulation of claim 1, wherein tacrolimus or its hydrate is present as an amorphous state in a mixture of ethylcellulose and hydroxypropylmethyl cellulose. 16. The sustained-release formulation of claim 15, wherein the weight ratio of the ethylcellulose to tacrolimus is 0.3:1, and the weight ratio of the hydroxypropylmethyl cellulose to tacrolimus is 0.3:1. 17. The sustained-release formulation of claim 16, wherein the excipient is lactose. 18. The sustained-release formulation of claim 17, wherein the weight ratio of lactose to tacrolimus is 2:1. 19. The sustained-release formulation of claim 18, wherein the solid dispersion composition has a particle size equal to or smaller than 212 .mu.m. 20. The sustained-release formulation of claim 3, wherein the water-insoluble polymer is ethylcellulose and the water soluble polymer is hydroxypropylmethyl cellulose. 21. The sustained-release formulation of claim 1, in a form of a powder, granule, tablet or capsule.