Patent EA-002482-B1 (EA)
Title: Sertraline salts and sustained-release dosage forms of sertraline
Inventor: AMENDE MARY TANYA
IPC: A61K9/26
Filed: 1998-06-15
Abstract: 1. A sustained-release dosage form suitable for oral administration to a mammal, comprising sertraline, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier  which dosage form releases sertraline into a use environment at a rate not exceeding 0.8 mgA/hr/kg,  provided said dosage form (1) releases not more than 70% of the sertraline contained therein within the first hour following entry into said use environment and (2) releases sertraline at a rate of at least 0.02 mgA/hr/kg. 2. A dosage form as defined in claim 1, wherein said sertraline is present as sertraline free base, sertraline hydrochloride, sertraline aspartate, sertraline acetate or sertraline lactate. 3. A dosage form as defined in claim 1, wherein said mammal is a human. 4. A dosage form as defined in claim 1, in the form of a matrix tablet which remains substantially intact during the period of sustained release. 5. A dosage form as defined in claim 1, in the form of a disintegrating matrix tablet. 6. A dosage form as defined in claim 1, in the form of a matrix tablet partially coated with a polymer which impedes the release of sertraline. 7. A dosage form as defined in claim 1, in the form of an osmotic tablet. 8. A dosage form as defined in claim 1, in the form of a membranecoated hydrogel tablet. 9. A dosage form as defined in claim 1, which is multiparticulate. 10. A dosage form as defined in claim 1, in the form of a membranecoated diffusion-based, capsule, tablet or multiparticulate. 11. A sustained-release dosage form suitable for administration to a mammal, comprising sertraline, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, which dosage form releases sertraline into a use environment at a rate not exceeding 40 mgA/hr,  provided said dosage form (1) releases not more than 70% of the sertraline contained therein within the first hour following entry into said use environment and (2) releases sertraline at a rate of at least 1 mgA/hr. 12. A dosage form as defined in claim 11 wherein said sertraline is present as sertraline free base, sertraline hydrochloride, sertraline aspartate, sertraline acetate or sertraline lactate. 13. A dosage form as defined in claim 11, wherein said mammal is a human. 14. A dosage form as defined in claim 11, in the form of a matrix tablet which remains substantially intact during the period of sustained release. 15. A dosage form as defined in claim 11, in the form of a disintegrating matrix tablet. 16. A dosage form as defined in claim 11, in the form of a matrix tablet partially coated with a polymer which impedes the release of sertraline. 17. A dosage form as defined in claim 11, in the form of an osmotic tablet. 18. A dosage form as defined in claim 11, in the form of a membranecoated hydrogel tablet. 19. A dosage form as defined in claim It, which is multiparticulate. 20. A dosage form as defined in claim 11, in the form of a membranecoated fiffusion-based tablet or multiparticulate. 21. A sustained release dosage form suitable for oral administration to a mammal, comprising sertraline or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, which dosage form releases sertraline at a rate less than 40 mgA/hr in vitro when dissolution tested in a USP-2 apparatus containing 900 ml of acetate buffer, pH 4.0, which is 0.075 M in NaCI, as follows: (1) if said dosage form is a sustained release tablet or a nontisintegrating sustained release capsule, said USP-2 apparatus is equipped with a paddle stirring at 50 rpm; (2) if said dosage form is a multiparticulate, said USP-2 apparatus is equipped with a paddle stirring at 100 rpm; provided said dosage form (a) releases not more than 70% of the sertraline contained therein within the first hour following initiation of testing and (b) releases sertraline at a rate of at least 1 mgA/hr. 22. A dosage form as defined in claim 21, wherein said sertraline is present as sertraline free base, sertraline hydrochloride, sertraline aspartate, sertraline acetate or sertraline lactate. 23. A dosage form as defined in claim 21, wherein said mammal is a human. 24. A dosage form as defined in claim 21, in the form of a matrix tablet which remains substantially intact during the period of sustained release. 25. A dosage form as defined in claim 21, in the form of a disintegrating matrix tablet. 26. A dosage form as defined in claim 21, in the form of a matrix tablet partially coated with a polymer which impedes the release of sertraline. 27. A dosage form as defined in claim 21, in the form of an osmotic tablet. 28. A dosage form as defined in claim 21, in the form of a membranecoated hydrogel tablet. 29. A dosage form as defined in claim 21, which is multiparticulate. 30. A dosage form as defined in claim 21, in the form of a membranecoated diffusion-based tablet or multiparticulate. 31. A temporally delayed plus sustained release dosage form suitable for oral administration to a mammal, comprising sertraline or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, which dosage form, following ingestion by said mammal, releases sertraline into said mammal's Gl tract at a rate less than 1 mgA/hr for an initial delay period of up to 3 hours, and which thereafter releases sertraline at a rate of from 1 mgA/hr to 40 mgA/hr, provided said dosage form releases not more than 70 % of the sertraline contained therein within the first hour after said delay period. 32. A dosage form as defined in claim 31, wherein said delay period is up to two hours. 33. A dosage form as defined in claim 31, wherein the rate of release following said delay period is from 1 mgA/hr to 30 mgA/hr. 34. A dosage form as defined in claim 31, wherein said sertraline is present as sertraline free base, sertraline hydrochloride, sertraline aspartate, sertraline acetate or sertraline lactate. 35. A dosage form as defined in claim 31, wherein said mammal is a human. 36. A temporally delayed plus sustained release dosage form suitable for administration to a mammal, said dosage form having an initial temporal delay period of up to 3 hours, comprising sertraline or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, which dosage form, when dissolution tested in vitro in a USP-2 apparatus containing 900 ml of acetate buffer, pH 4.0, which is 0.075 M in NaCI, releases sertraline at a rate less than 1 mgA/hr for a period corresponding to said delay period and, thereafter, releases sertraline at a rate of from 1 mgA/hr to 40 mgA/hr, provided the dosage form releases not more than 70 % of the remaining sertraline contained therein within the first hour following said delay. 37. A dosage form as defined in claim 36, wherein said delay period is up to two hours. 38. A dosage form as defined in claim 36, wherein the rate of release following said delay period is from 1 mgA/hr to 30 mgA/hr. 39. A dosage form as defined in claim 36, wherein said sertraline is present as sertraline free base, sertraline hydrochloride, sertraline aspartate, sertraline acetate or sertraline lactate. 40. A dosage form as defined in claim 36, wherein said mammal is a human. 41. A dosage form as defined in claim 36, in the form of a tablet. 42. A dosage form as defined in claim 36, which is multiparticulate. 43. A spatially delayed plus sustained release dosage form suitable for oral administration to a mammal, comprising sertraline or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier,  which dosage form, following ingestion by said mammal, releases sertraline into said mammal's stomach at a rate less than 1 mgAlhr, and which, after having passed into said mammal's small intestine, effects sustained release at a rate of from 1 mgA/hr to 40 mgA/hr, provided said dosage form releases not more than 70 % of the sertraline contained therein within the first hour after passing into said mammal's small intestine. 44. A dosage form as defined in claim 43, wherein the onset of sustained release is pH-triggered. 45. A dosage form as defined in claim 44, comprising a sustained release dosage form coated with a polymer that prevents release of sertraline at the pH of the stomach, but which is permeable to sertraline at the pH of the small intestine. 46. A dosage form as defined in claim 44, wherein said sustained release dosage form is multiparticulate. 47. A dosage form as defined in claim 44 wherein said sustained release dosage form is a tablet. 48. A dosage form as defined in claim 43, which is enzyme-triggered. 49. A dosage form as defined in claim 48, comprising a sustained release dosage form coated with a membrane having a hydrophobic liquid entrained within the pores thereof, said hydrophobic liquid being substantially impermeable to water and sertraline, but capable of changing, through enzymatic degradation, so that said membrane becomes substantially permeable to water and sertraline when said dosage form moves into the environment of the small intestinal lumen. 50. A dosage form as defined in claim 48, wherein said sustained release dosage form is multiparticulate. 51. A dosage form as defined in claim 48, wherein said sustained release dosage form is a matrix. 52. A dosage form as defined in claim 43, wherein said sertraline is present as sertraline free base, sertraline hydrochloride, sertraline aspartate, sertraline acetate or sertraline lactate. 53. A dosage form as defined in claim 43, wherein said mammal is a human. 54. A sustained release pH-triggered dosage form suitable for oral administration to a mammal, said dosage form having an initial delay period prior to the onset of sustained release, comprising sertraline or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, which dosage form, when tested in vitro in a USP-2 apparatus, releases sertraline into 0.1 N HCI at a rate less than 1 mgA/hr for 1 hou