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1. WO2008100106 - PRÉPARATION À LIBÉRATION CONTRÔLÉE CONTENANT DU CILOSTAZOL ET SON PROCÉDÉ DE FABRICATION

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

What is claimed is:

1. A controlled release preparation of cilostazol which comprises:
(A) particles comprising cilostazol or its pharmaceutically acceptable salt uniformly dispersed in a solubilizing agent, and
(B) an erodible material for forming a hydrogel in which said particles are dispersed therein.

2. The controlled release preparation of claim 1, which comprises the cilostazol or its pharmaceutically acceptable salt in an amount ranging from 10 to 80 % by weight; the solubilizing agent in an amount ranging from 0.1 to 50 % by weight; and the erodible material for forming a hydrogel in an amount ranging from 5 to 80 % by weight, based on the total weight of the preparation.

3. The controlled release preparation of claim 1, wherein the solubilizing agent is selected from the group consisting of polyvinylpyrrolidone, copovidone, polyethyleneglycol, hydroxyalkylcellulose, hydroxypropylmethylcellulose, poloxamer, polyvinylalcohol, cyclodextrin, surfactant, and a mixture thereof.

4. The controlled release preparation of claim 3, wherein the surfactant is selected from the group consisting of poly(oxyethylene) sorbitan fatty acid ester, poly(oxyethylene) stearate, poly(oxyethylene) alkylether, polyglycolized glyceride, poly(oxyethylene) castor oil, sorbitan fatty acid ester, poloxamer, fatty acid salt, bile salt, alkylsulfate, lecithin, mixed micelles of bile salt and lecithin, sugar ester vitamin E(polyethylene glycol 1000)succinate (TPGS), sodium lauryl sulfate, and a mixture thereof.

5. The controlled release preparation of claim 1, wherein the erodible material for forming the hydrogel is selected from the group consisting of polyethyleneoxide, hydroxyalkylcellulose, hydroxypropyl alkylcellulose, polyvinylalcohol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, propylene glycol alginate, carbopol, sodium alginate, xanthan gum, locust bean gum, cellulose gum, gellan gum, tragacanth gum, karaya gum, gua gum, acasia gum, and a mixture thereof.

6. The controlled release preparation of claim 1, which further comprises a pharmaceutically acceptable additive.

7. The controlled release preparation of claim 6, wherein the pharmaceutically acceptable additive is selected from the group consisting of a diluent, a binding agent, a swelling agent, a lubricant, and a mixture thereof.

8. The controlled release preparation of claim 7, wherein the diluent is selected from the group consisting of lactose, dextrin, mannitol, sorbitol, starch, microcrystalline cellulose, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, calcium carbonate, sugars, and a mixture thereof.

9. The controlled release preparation of claim 7, wherein the binding agent is selected from the group consisting of polyvinylpyrrolidone, copovidone, gelatin, starch, sucrose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylalkylcellulose, and a mixture thereof.

10. The controlled release preparation of claim 7, wherein the swelling agent is selected from the group consisting of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, cross-linked calcium carboxymethylcellulose, cross-linked carboxymethylcellulose, sodium starch glycolate, carboxymethyl starch, sodium carboxymethyl starch, potassium methacrylate-divinylbenzene copolymer, amylose, cross-linked amylose, a starch derivative, microcrystalline cellulose, a cellulose derivative, cyclodextrin, a dextrin derivative, and a mixture thereof.

11. The controlled release preparation of claim 7, wherein the lubricant is selected from the group consisting of stearic acid, stearate, talc, corn starch, carnauba wax, light anhydrous silicic acid, magnesium silicate, synthetic aluminum silicate, hardened oil, white lead, titanium oxide, microcrystallinecellulose, macrogol 4000 and 6000, isopropyl myristate, calcium hydrogen phosphate, and a mixture thereof.

12. The controlled release preparation of claim 1, which further comprise a coating layer containing a coating agent.

13. The controlled release preparation of claim 12, wherein the coating agent is selected from the group consisting of ethylcellulose, shellac, ammonio methacrylate copolymer, polyvinylacetate, polyvinylpyrrolidone, polyvinylalcohol, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, hydroxypentylcellulose, hydroxypropylmethylcellulose, hydroxypropylbutylcellulose, hydroxypropylpentylcellulose, hydroxyalkylcellulosephthalate, sodium celluloseacetatephthalate, celluloseacetylphthalate, celluloseetherphthalate, anionic copolymer of methacrylic acid and methyl or ethyl ester methacrylate, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetylsuccinate, cellulose acetylphthalate, Opadry, and a mixture thereof.

14. A method for preparing the controlled release preparation of cilostazol of claim 1, which comprises:
(1) mixing cilostazol or its pharmaceutically acceptable salt with a solubilizing agent, and subjecting the resulting mixture to granulation using a solid dispersing method to produce particles; and
(2) adding an erodible material for forming a hydrogel to the particles obtained in step (1), and subjecting the resulting mixture to granulation to produce granules having the particles encased therein.

15. The method of claim 14, wherein the cilostazol or its pharmaceutically acceptable salt is used in an amount ranging from 10 to 80 % by weight based on the total weight of the preparation.

16. The method of claim 14, wherein the solubilizing agent is used in an amount ranging from 0.1 to 50 % by weight based on the total weight of the preparation.

17. The method of claim 14, wherein the erodible material for forming the hydrogel is used in an amount ranging from 5 to 80 % by weight based on the total weight of the preparation.

18. The method of claim 14, which further comprises adding a pharmaceutically acceptable additive to the mixture before performing step (1) or (2), or to the granules obtained in step (2).

19. The method of claim 18, wherein the pharmaceutically acceptable additive is selected from the group consisting of a diluent, a binding agent, a swelling agent, a lubricant, and a mixture thereof.

20. The method of claim 14, which further comprises coating the granules obtained in step (2) with a coating agent.