초록 ▼

The present invention relates to a spray-dried powder and method for its manufacture. A spray dried powder containing a pharmaceutical active substance and one or more 1,4 O-linked saccharose derivatives chosen from the compounds: 1,4 O-linked D-gal-saccharose (lactosucrose), 1,4 O-linked D-glu-sacc

The present invention relates to a spray-dried powder and method for its manufacture. A spray dried powder containing a pharmaceutical active substance and one or more 1,4 O-linked saccharose derivatives chosen from the compounds: 1,4 O-linked D-gal-saccharose (lactosucrose), 1,4 O-linked D-glu-saccharose (glucosyl sucrose) or 1,4 O-linked glu-glu-saccharose (maltosyl sucrose). Preferred combinations are such that they contain glucosyl and maltosyl sucrose.

대표청구항 ▼

The invention claimed is: 1. A powder comprising particles of a pharmaceutical active substance, and one or more 1,4 O-linked saccharose derivatives chosen from the compounds: 1,4 O-linked D-gal-saccharose (lactosucrose), 1,4 O-linked D-glu-saccharose (glucosyl sucrose) and 1,4 O-linked glu-glu-sac

The invention claimed is: 1. A powder comprising particles of a pharmaceutical active substance, and one or more 1,4 O-linked saccharose derivatives chosen from the compounds: 1,4 O-linked D-gal-saccharose (lactosucrose), 1,4 O-linked D-glu-saccharose (glucosyl sucrose) and 1,4 O-linked glu-glu-saccharose (maltosyl sucrose), wherein the powder is a spray-dried powder, and wherein the particles in the spray-dried powder have a mass median aerodynamic diameter (MMAD) of between 1 and 7.5 μm. 2. The spray dried powder according to claim 1, wherein the saccharose derivative is lactosucrose. 3. The spray dried powder according to claim 2, wherein the spray dried powder in addition comprises one or more mono-, di- and/or polysaccharides. 4. The spray dried powder according to claim 3, wherein the spray-dried powder comprises in addition lactose and saccharose. 5. The spray dried powder according to any one of claims 2 to 4, wherein lactosucrose comprises at least 55% (w/w) by weight of the total sugar content contained in the powder. 6. The spray dried powder according to claim 1, comprising glucosyl sucrose and maltosyl sucrose. 7. The spray dried powder according to claim 6, wherein the spray dried powder in addition comprises one or more mono-, di- and/or polysaccharides. 8. The spray dried powder according to claim 7, wherein the spray-dried powder comprises in addition fructose, glucose and/or saccharose. 9. The spray dried powder according to any one of claims 6 to 8, wherein glucosyl sucrose and maltosyl sucrose comprise at least 25% (w/w) by weight of the total sugar content contained in the powder. 10. The spray dried powder according to claim 9, wherein maltosyl sucrose and glucosyl sucrose comprise at least 18% (w/w) by weight of the total sugar content contained in the powder. 11. The spray dried powder according to claim 1, wherein the spray dried powder comprises a sugar mixture comprising at least one 1,4 O-linked saccharose derivative, wherein the sugar mixture is between 25 and 99.99% (w/w) of the dry mass of the powder. 12. The spray dried powder according to claim 11, wherein the proportion of the pharmaceutical active substance is between 0.01 and 75% (w/w) of the dry mass of the powder. 13. The spray dried powder according to claim 12, wherein the pharmaceutical active substance is a biological macromolecule. 14. The spray dried powder according to claim 13, wherein the dry mass of the spray-dried powder comprises between 25 and 90% (w/w) of at least one 1,4 O-linked saccharose derivative or a sugar mixture comprising at least one 1,4 O-linked saccharose derivative and up to 75% (w/w) of a pharmaceutical active substance, wherein the proportion of lactosucrose, maltosyl sucrose and/or glycosyl sucrose comprise at least 20% (w/w) of the dry mass of the powder and the total of the weight percents relative to the powder is a maximum of 100% (w/w). 15. The spray dried powder according to claim 14, wherein the spray dried powder comprises one or more other pharmaceutically compatible excipients and/or one or more salts. 16. The spray dried powder according to claim 15, wherein the excipient is isoleucine. 17. The spray dried powder according to claim 15, wherein the excipient is a peptide. 18. The spray dried powder according to claim 17, wherein the excipient is a tri-peptide. 19. The spray dried powder according to claim 18, wherein the tri-peptide is tri-leucine. 20. The spray dried powder according to claim 16, wherein the dry mass of the spray-dried powder comprises between 25 and 90% (w/w) of at least one 1,4 O-linked saccharose derivative or a sugar mixture comprising at least one 1,4 O-linked saccharose derivative and between 1 and 19.99% (w/w) isoleucine, wherein the total of the weight percentages does not exceed 100% (w/w). 21. The spray dried powder according to claim 18, wherein the dry mass of the spray-dried powder comprises between 25 and 90% (w/w) of at least one 1,4 O-linked saccharose derivative or a sugar mixture comprising at least one 1,4 O-linked saccharose derivative and between 1 and 39% (w/w) of a tri-peptide. 22. The spray dried powder according to claim 1, wherein the particles in the powder have a mass median diameter (MMD) of between 1 and 10 μm. 23. A pharmaceutical composition comprising a spray-dried powder according to claim 1. 24. A process for manufacturing the spray-dried powder according to claim 1, comprising a) dissolving or suspending the pharmaceutical active substance in an aqueous solution/suspension; b) dissolving or suspending one or more 1,4 O-linked saccharose derivatives chosen from the group comprising the compounds lactosucrose, glucosyl sucrose or maltosyl sucrose or a sugar mixture comprising at least one of these 1,4 O-linked saccharose derivatives in an aqueous solution/suspension; c) mixing the solutions/suspensions to a combined solution/suspension; d) spraying the combined solution/suspension at a temperature of less than 200/120° C. (inflow/outflow temperature) to a dried mass. 25. The process according to claim 24, wherein the pharmaceutical active substance is a biological macro-molecule. 26. The process according to claim 24, wherein the saccharose derivative is lactosucrose. 27. The process according to claim 26, wherein the combined solution/suspension comprises one or more mono-, di- or polysaccharides. 28. The process according to claim 27, wherein the combined solution/suspension in addition comprises lactose and saccharose. 29. The process according to claim 28, wherein lactosucrose comprises at least 55% (w/w) of the total sugar content present in the combined solution/suspension. 30. The process according to claim 24, wherein the saccharose derivative is a mixture of glucosyl sucrose and maltosyl sucrose. 31. The process according to claim 30, wherein the combined solution/suspension comprises one or more mono-, di- or polysaccharides. 32. The process according to claim 31, wherein the combined solution/suspension comprises fructose, saccharose and/or glucose. 33. The process according to claim 32, wherein glucosyl-sucrose and maltosyl-sucrose comprise at least 25% (w/w) by weight of the total sugar content present in the combined solution/suspension. 34. The process according to claim 33, wherein maltosyl-sucrose and glycosyl sucrose comprise at least 18% (w/w) by weight of the total sugar content present in the combined solution/suspension. 35. The process according to claim 34, wherein the 1,4 O-linked saccharose derivative or a sugar mixture comprising at least one 1,4 O-linked saccharose derivative comprises between 25 and 99.99% (w/w) of the dry mass of the combined solution/suspension. 36. The process according to claim 35, wherein the pharmaceutical active substance comprises between 0.01 and 75% (w/w) of the dry mass of the combined solution/suspension. 37. The process according to claim 36, wherein the combined solution/suspension comprises one or more other pharmaceutically acceptable excipients and/or one or more salts. 38. The process according to claim 37, wherein the excipient is an amino acid. 39. The process according to claim 38, wherein the amino acid is isoleucine. 40. The process according to claim 37, wherein the excipient is a peptide. 41. The process according to claim 40, wherein the excipient is a tri-peptide. 42. The process according to claim 41, wherein the tri-peptide is tri-isoleucine. 43. The process according to claim 39, wherein the dry mass of the combined solution/suspension comprises between 25 and 90% (w/w) of at least one 1,4 O-linked saccharose derivative or a sugar mixture comprising at least one 1,4 O-linked saccharose derivative and between 1 and 19.99% (w/w) isoleucine. 44. The process according to claim 41, wherein the dry mass of the combined solution/suspension comprises between 60 and 90% (w/w) of at least one 1,4 O-linked saccharose derivative or a sugar mixture comprising at least one 1,4 O-linked saccharose derivative and between 1 and 39% (w/w) of a tri-peptide. 45. The process according to claim 24, wherein the temperature is less than 186/96° C. (inflow/outflow temperature).