Patent EA-003943-B1 (EA)
Title: Microgranules protected from solution in gastric fluid, method for obtaining and pharmaceutical preparations
Inventor: CRIERE BRUNO
IPC: A61P35/00
Filed: 2000-05-19
Abstract: 1. Microgranules, comprising a gastric proton pump inhibitor, with the exception of omeprazole, each comprising an active layer comprising the active principle and an outer layer for protection in gastric fluid, characterized in that the active layer and the layer for protection in gastric fluid each comprises at least one hydrophobic substance. 2. The microgranules as claimed in claim 1, characterized in the hydrophobic substance present in the active layer represents 5 to 40% by weight of the active principle. 3. The microgranules as claimed in either of claims 1 and 2, characterized in that the hydrophobic substance present in the active layer is chosen from silicone oils. 4. The microgranules as claimed in one of claims 1 to 3, characterized in that the active layer comprises 5 to 15%, with respect to the weight of active principle, of a nonionic surfactant, for example a polysorbate. 5. The microgranules as claimed in one of claims 1 to 4, characterized in that the active layer comprises a binder, such as hydroxypropylmethyl-cellulose. 6. The microgranules as claimed in one of the preceding claims, characterized in that the layer for protection in gastric fluid is composed of 90 to 95% of film-forming agent and of an equal amount of plasticizer and of hydrophobia substance. 7. The microgranules as claimed in one of the preceding claims, characterized in that the hydrophobic substance present in the layer for protection in gastric fluid is chosen from the glycerides. 8. The microgranules as claimed in either of claims 6 and 7, characterized in that the plasticizer represents 5 to 20% by weight of the dry glaze of the film-forming agent. 9. The microgranules as claimed in one of claims 6 to 8, characterized in that the film-forming agent representing from 15 to 60% of the dry polymer deposit with respect to the mass of the microgranule. 10. The microgranules as claimed in one of claims 6 to 9, characterized in that the film-forming agent is a copolymer of methacrylic acid, such as Eudragit L30D(RTM). 11. The microgranules as claimed in one of the preceding claims, characterized in that at least one intermediate layer is inserted between the active layer and the layer for protection in gastric fluid. 12. The microgranules as claimed in claim 11, characterized in that each microgranule comprises: - a layer of active principle comprising an active principle, a binder chosen from pharmaceutically acceptable binders, a hydrophobic substance and a nonionic surfactant, - a first protective layer comprising one or more pharmaceutically acceptable hydrophobia diluent substances and a binder, - a second hydrophobic protective layer comprising a coating agent and a hydrophobic plasticizer, - a layer for protection in gastric fluid comprising an enteric film-forming agent, a hydrophilic plasticizer and a hydrophobic substance. 13. The microgranules as claimed in claim 12, characterized in that the first protective layer comprises mannitol as diluent substance. 14. The microgranules as claimed in either of claims 12 and 13, characterized in that the second protective layer is composed of a water-soluble coating agent, such as hydroxypropylmethyl-cellulose, and of a hydrophobic plasticizer, such as Myvacet(RTM). 15. The microgranules as claimed in one of the preceding claims, characterized in that the active layer is applied to a neutral nucleus and in that the particle size of the microgranule is between 0.3 and 3 mm. 16. The microgranules as claimed in one of the preceding claims, characterized in that it comprises: - 35 to 45% of neutral materials, - 15 to 25% of mannitol, - 5 to 15% of active principle, - 8 to 15% of hydroxypropylmethylcellulose, - 15 to 33% of a copolymer of methacrylic acid, - 0.5 to 1.5% of a silicone oil, - 0.5 to 1.5% of a nonionic surfactant, - 1 to 6% of a plasticizer, - 1 to 6% of a glyceride, - 1 to 2% of talc, the percentages being expressed by mass in ratio to the mass of microgranules. 17. A process for the preparation of the microgranules as claimed in one of the preceding claims, characterized in that it is carried out in aqueous medium. 18. The process as claimed in claim 17, characterized in that application is carried out in a fluidized air bed. 19. A pharmaceutical preparation comprising the microgranule as claimed in one of claims 1 to 16 or obtained according to the process of either of claims 17 and 18, comprising 5 to 60 mg approximately of active principle.