Production of Solid Solutions Based on Poorly-Soluble Active Substances by a Short-Term Heating and Rapid Drying

• US 20080248117A1
• Filed: 05/31/2006
• Published: 10/09/2008
• Est. Priority Date: 06/09/2005
• Status: Abandoned Application

• Current Assignee: BASF AG (BASF SE)
• Original Assignee: BASF AG (BASF SE)
• Inventors: Kolter, Karl, Ascherl, Hermann, Schoenherr, Michael
• Application Number:
  US11/916,074
• Publication Number:
  US 20080248117A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds

Abstract

A process for producing solid solutions in powder or granule form of slightly soluble substances in which the slightly soluble substance is in the form of a molecular dispersion in an excipient matrix, by atomizing a solution of the active ingredient and of the matrix excipients, which comprises heating an aqueous suspension of the slightly soluble substance in the presence of the matrix excipients to temperatures above the boiling point under atmospheric pressure, and dissolving the slightly soluble substance, and subsequently converting the solution of the slightly soluble substance and of the matrix excipients by atomizing and drying into a solid form, where the temperature of the spray solution before feeding into the atomizing apparatus is 90° C. to 350° C.

Claims

1-28. -28. (canceled)

29. A process for producing solid solutions in powder or granule form of slightly soluble substances, wherein said slightly soluble substance is in the form of a molecular dispersion in an excipient matrix, comprising atomizing a solution of the active ingredient and matrix excipients by heating an aqueous suspension of said slightly soluble substance in the presence of the matrix excipients to temperatures above the boiling point under atmospheric pressure, dissolving the slightly soluble substance, and converting said solution of slightly soluble substance and matrix excipients by atomizing and drying into a solid form, wherein the temperature of the spray solution before feeding into the atomizing apparatus is in the range of from 90°

C. to 350°

C.

30. The process of claim 29, wherein the temperature of the spray solution before atomizing is in the range of from 110 to 300°

C. and said active ingredient is in dissolved form.

31. The process of claim 29, wherein the temperature of the spray solution before atomizing is in the range of from 120 to 250°

C. and said active ingredient is in dissolved form.

32. The process of claim 29, wherein the residence time of said active ingredient at temperatures above 90°

C. is less than 180 seconds.

33. The process of claim 29, wherein the residence time of said active ingredient at temperatures above 90°

C. is less than 60 seconds.

34. The process of claim 29, wherein the residence time of said active ingredient at temperatures above 90°

C. is less than 15 seconds.

35. The process of claim 29, wherein the concentration of said slightly soluble substance in the excipient matrix is from 1 to 50% by weight

36. The process of claim 29, wherein the concentration of said slightly soluble substance in the excipient matrix is from 10 to 50% by weight.

37. The process of claim 29, wherein the concentration of said slightly soluble substance in the excipient matrix is from 20 to 50% by weight.

38. The process of claim 29, wherein said matrix excipients comprise amide groups.

39. The process of claim 29, wherein said matrix excipients comprise homo- or copolymers of N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylformamide, or N-vinylacetamide.

40. The process of claim 29, wherein said solid solutions further comprise surfactants having a HLB above 10.

41. The process of claim 29, wherein said solid solutions further comprise cosolubilizers having a HLB below 10.

42. The process of claim 29, wherein said spray solution comprises an adsorbent.

43. The process of claim 29, wherein said suspension of the active ingredient is heated by a heat exchanger.

44. The process of claim 29, wherein heating of said suspension of the active ingredient is achieved by mixing with a hot stream of liquid or a hot stream of vapor.

45. The process of claim 44, wherein the ratio of said suspension of the active ingredient to said hot stream of liquid is from 9:

1 to 1;

9.

46. The process of claim 44, wherein the ratio of said suspension of the active ingredient to said hot stream of liquid is from 7:

3 to 3;

7.

47. The process of claim 44, wherein the temperature of said hot stream of liquid or vapor is in the range of from 110 to 500°

C.

48. The process of claim 44, wherein the temperature of said hot stream of liquid or vapor is in the range of from 150 to 400°

C.

49. The process of claim 48, wherein the temperature of said hot stream of liquid or vapor is in the range of from 180 to 300°

C.

50. The process of claim 29, wherein said drying is achieved by atomizing drying or of by fluidized bed spray granulation.

51. The process of claim 29, wherein an adsorbent or dusting agent is blown into the spray tower during atomizing drying.

52. The process of claim 29, wherein said slightly soluble active ingredients are medicinal substances, vitamins, carotenoids, or nutraceuticals.

53. A solid solution in the form of a powder or granules prepared by the process of claim 29.

54. The powder or granules of claim 53, comprising a) 1 to 50% by weight of active ingredient, b) 10 to 99% by weight of a water-soluble matrix excipient, c) 0 to 30% by weight of solubilizers, d) 0 to 30% by weight of cosolubilizers and e) 0 to 50% by weight of further customary excipients.

55. A pharmaceutical dosage form, food product, or dietary supplement comprising the powder or granules of claim 53.