High-volume on-line spectroscopic composition testing of manufactured pharmaceutical dosage units

• US 6,690,464 B1
• Filed: 02/18/2000
• Issued: 02/10/2004
• Est. Priority Date: 02/19/1999
• Status: Expired due to Fees

• Current Assignee: Malvern Instruments, Inc, Department of Health and Human Services (State of Victoria)
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America), Spectral Dimensions, Inc. (Spectris PLC)
• Inventors: Lewis, E. Neil, Strachan, David J., Kidder, Linda H.
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): LAUCHMAN, LAYLA G
• Application Number:
  US09/507,293
• Time in Patent Office: 1,453 Days
• Field of Search: 356/326, 356/416, 250/339-2-3, 250/332
• US Class Current: 356/326
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence

Abstract

Disclosed are pharmaceutical dosage unit manufacturing process control apparatus and methods. These can include acquiring a plurality of multi-pixel images of a flow of pharmaceutical dosage units at different wavelengths along an axis that is perpendicular to a direction of the flow of pharmaceutical dosage units, processing the images acquired in the step of acquiring, and providing an indication about the flow of pharmaceutical dosage units based on the step of processing.

Claims

1. A pharmaceutical dosage unit manufacturing process control apparatus, comprising:

an image sensor including an array of detector elements located generally along an axis that is perpendicular to a direction of a flow of pharmaceutical dosage units,

a spectrally selective element located in an optical path between a radiation source, the flow of pharmaceutical dosage units, and the image sensor, and

a spectral processor responsive to an output of the array sensor and having an output port, wherein the spectral processor includes a color mapping module operative to map spectral information into a color image including differently colored areas that correspond to different parts of the flow of pharmaceutical dosage units having differing responses to different wavelengths.

2. The apparatus of claim 1 further including an additional processor operative to evaluate the differently colored areas, the additional processor having an input responsive to the mapping module and an output for providing information about the areas.

3. The apparatus of claim 1 wherein the mapping module is operative to shift a plurality of the wavelengths in a similar manner.

4. The apparatus of claim 1 wherein the spectral processor includes a spectral comparison module operative to compare spectral signatures from a library of known spectral signatures with spectral information acquired from the image sensor.

5. The apparatus of claim 4 wherein the spectral comparison module is operative to perform spectral comparisons between the spectral information acquired from the image sensor and spectral signatures for known ingredients in a pharmaceutical composition of the dosage units.

6. The apparatus of claim 4 wherein the processor is operative to receive, identify, and store newly detected spectral signatures reported by the spectral comparison module.

7. The apparatus of claim 4 wherein the library of known spectral signatures includes a plurality of spectral signatures for known defects.

8. The apparatus of claim 7 wherein the processor is operative to receive, identify, and store spectral signatures for newly detected defects reported by the spectral comparison module.

9. The apparatus of claim 1 wherein the image sensor is a two-dimensional array sensor that further includes detectors located generally along an axis that is parallel to the direction of the flow of pharmaceutical dosage units.

10. The apparatus of claim 9 wherein the spectrally selective element includes a diffraction grating.

12. The apparatus of claim 1 wherein the image sensor is an infrared image sensor.

13. The apparatus of claim 1 wherein the image sensor is a near infrared image sensor.

14. The apparatus of claim 1 further including the radiation source directed at the flow of pharmaceutical dosage units at a position to which the array sensor is responsive.

15. The apparatus of claim 14 wherein the radiation source is an infrared radiation source.

22. The apparatus of claim 1 wherein the spectral processor is operative to receive image data from the image sensor at a rate that is independent of a rate of advance of the flow of pharmaceutical dosage units.

23. The apparatus of claim 1 wherein the spectral processor is operative to perform univariate spectral manipulations on a spectral data set acquired from the image sensor.

24. The apparatus of claim 1 wherein the spectral processor is operative to perform multivariate spectral manipulations on a spectral data set acquired from the image sensor.

25. The apparatus of claim 1 wherein the spectrally selective element is a filter having filter characteristics that vary along the direction of flow of pharmaceutical dosage units.

26. The apparatus of claim 25 wherein the spectrally selective element is a continuously gradeable filter.

27. The apparatus of claim 1 wherein the spectrally selective element includes a system that simultaneously projects a plurality of spectrally-discrete versions of a same image onto the image sensor.

11. A pharmaceutical dosage unit manufacturing process control apparatus, comprising:

an image sensor including an array of detector elements located generally along an axis that is perpendicular to a direction of a flow of pharmaceutical dosage units, wherein the image sensor is a two-dimensional array sensor that further includes detectors located generally along an axis that is parallel to the direction of the flow of pharmaceutical dosage units,

a spectrally selective element located in an optical path between a radiation source, the flow of pharmaceutical dosage units, and the image sensor, and

a spectral processor responsive to an output of the array sensor and having an output port, wherein the spectral processor includes a color mapping module operative to map spectral information into a color image including differently colored areas that correspond to different parts of the flow of pharmaceutical dosage units having differing responses to different wavelengths.

16. A pharmaceutical dosage unit manufacturing process control apparatus, comprising:

an image sensor including an array of detector elements located generally along an axis that is perpendicular to a direction of a flow of pharmaceutical dosage units, wherein the flow of pharmaceutical dosage units includes a series of dosage units located in rows generally perpendicular to the direction of the flow of pharmaceutical dosage units and wherein the image sensor includes, for each of the dosage units in a row, a plurality of detectors along the axis that is perpendicular to the direction of the flow of pharmaceutical dosage units,

a spectrally selective element located in an optical path between a radiation source, the flow of pharmaceutical dosage units, and the image sensor, and

a spectral processor responsive to an output of the array sensor and having an output port.

17. A pharmaceutical dosage unit manufacturing process control apparatus, comprising:

an image sensor including an array of detector elements located generally along an axis that is perpendicular to a direction of a flow of pharmaceutical dosage units,

a spectrally selective element located in an optical path between a radiation source, the flow of pharmaceutical dosage units, and the image sensor, and

a spectral processor responsive to an output of the array sensor and having an output port, wherein the spectral processor is a real-time processor operative to process the images at a rate that is at least equal to a rate at which images are acquired by the image sensor.

18. The apparatus of claim 17 wherein the spectral processor includes a spectral comparison module operative to compare spectral information received by the image sensor from a reference sample located proximate the flow of pharmaceutical dosage units with spectral information received by the image sensor from the flow of pharmaceutical dosage units.

19. The apparatus of claim 17 further including an image processor responsive to the output port of the spectral processor and operative to evaluate information from the spectral processor.

20. The apparatus of claim 17 wherein the spectral processor is operative to sequentially process spectral data for each line image acquired by the image sensor.

21. The apparatus of claim 20 wherein the spectral processor is operative to receive image data from the image sensor at a rate that is independent of a rate of advance of the flow of pharmaceutical dosage units.

28. A pharmaceutical dosage unit manufacturing process control apparatus, comprising:

means for acquiring a plurality of multi-pixel images of a flow of pharmaceutical dosage units at different wavelengths along an axis that is perpendicular to a direction of the flow of pharmaceutical dosage units, and

means for processing the images acquired by the means for acquiring.

29. A pharmaceutical dosage unit manufacturing process control method, comprising:

acquiring a plurality of multi-pixel images of a flow of pharmaceutical dosage units at different wavelengths along an axis that is perpendicular to a direction of the flow of pharmaceutical dosage units,

processing the images acquired in the step of acquiring, and

providing an indication about the flow of pharmaceutical dosage units based on the step of processing.

30. A pharmaceutical dosage unit manufacturing process control apparatus, comprising:

means for acquiring a plurality of multi-pixel line images of a flow of pharmaceutical dosage units along an axis that is perpendicular to a direction of the flow of pharmaceutical dosage units, and

means for processing the images acquired in the step of acquiring as they are received.

31. The apparatus of claim 30 wherein the means for acquiring is operative to acquire the multi-pixel line images at a rate that is independent of a rate of advance of the flow of pharmaceutical dosage units.

32. A pharmaceutical dosage unit manufacturing process control method, comprising:

acquiring a plurality of multi-pixel line images of a flow of pharmaceutical dosage units along an axis that is perpendicular to a direction of the flow of pharmaceutical dosage units,

processing the images acquired in the step of acquiring as they are received, and

providing an indication about the flow of pharmaceutical dosage units based on the step of processing.

33. The method of claim 32 wherein the step of acquiring is operative to acquire the multi-pixel line images at a rate that is independent of a rate of advance of the flow of pharmaceutical dosage units.

34. The method of claim 32 wherein the step of acquiring takes place through individual packaging cells for the dosage units.

35. A process control apparatus, comprising:

means for acquiring a spectral data set from a process flow, the spectral data set expressing the response of areas of a surface of the process flow to different wavelengths of radiation, and

means for mapping the spectral data set to a color image including differently colored areas that correspond to different ones of the parts of the process flow having differing responses to the different wavelengths.

36. The apparatus of claim 35 further including means for evaluating the differently colored areas, having an input responsive to the means for mapping and an output for providing information about the areas.

37. A process control method, comprising:

acquiring a spectral data set from a process flow, the spectral data set expressing the response of areas of a surface of the process flow to different wavelengths of radiation, and

mapping the spectral data set to a color image including differently colored areas that correspond to different ones of the parts of the process flow having differing responses to the different wavelengths.

38. A process control apparatus, comprising:

means for acquiring a plurality of multi-pixel images of a process flow at different wavelengths along an axis that is perpendicular to a direction of the process flow, and

means for comparing spectral signatures from a library of known spectral signatures with spectral information acquired in the step of acquiring.

39. The apparatus of claim 38 wherein the means for comparing is operative to receive, identify, and store spectral signatures for new defects detected by the means for comparing.

40. The apparatus of claim 38 wherein the means for comparing is operative to compare spectral signatures for known defects with the spectral information acquired in by the means for acquiring.

41. A process control method, comprising:

acquiring a plurality of multi-pixel images of a process flow at different wavelengths along an axis that is perpendicular to a direction of the process flow,

comparing spectral signatures from a library of known spectral signatures, including a plurality of spectral signatures for known defects, with spectral information acquired in the step of acquiring, and

providing an indication about the flow of pharmaceutical dosage units based on the step of processing.

42. The method of claim 41 further including the steps of automatically identifying and storing spectral signatures for new defects detected in the step of comparing.

43. The apparatus of claim 41 wherein the step of comparing is operative to compare spectral signatures for known defects with the spectral information acquired in the step of acquiring.

44. A quality control apparatus for a pharmaceutical composition, comprising:

a two-dimensional array sensor including a two-dimensional array of detector elements,

a spectrally selective element located in an optical path between a radiation source, the flow of pharmaceutical dosage units, and the two-dimensional array sensor, and

a spectral processor responsive to an output of the array sensor and having an output port, wherein the spectral processor includes a mapping module operative to map spectral information into an image including different areas corresponding to different components of the pharmaceutical composition having differing responses to different wavelengths.

45. The apparatus of claim 44 wherein the spectral processor includes a spectral comparison module operative to compare one or more known spectral signatures with spectral information acquired from the array sensor.

46. The apparatus of claim 45 wherein the spectral comparison module is operative to perform spectral comparisons between the spectral information acquired from the array sensor and spectral signatures for at least one known ingredient in the pharmaceutical composition.

47. The apparatus of claim 45 wherein the spectral comparison module is operative to perform spectral comparisons between the spectral information acquired from the array sensor and spectral signatures for a plurality of known ingredients in the pharmaceutical composition.

48. The apparatus of claim 44 wherein the spectral processor includes a spectral comparison module operative to compare spectral information received by the array sensor from a reference sample with spectral information received by the array sensor.

49. The apparatus of claim 44 wherein the spectrally selective element includes a diffraction grating.

50. The apparatus of claim 44 further including an image processor responsive to the output port of the spectral processor and operative to evaluate information from the spectral processor.

51. The apparatus of claim 44 wherein the array sensor is an infrared image sensor.

52. The apparatus of claim 44 wherein the array sensor is a near infrared image sensor.

53. The apparatus of claim 44 further including the radiation source directed at the pharmaceutical composition at a position to which the array sensor is responsive.

54. The apparatus of claim 53 wherein the radiation source is an infrared radiation source.

55. The apparatus of claim 44 wherein the spectral processor is operative to perform spectral manipulations on a spectral data set that includes image values at different wavelengths for each of a plurality of pixels corresponding to ones of the detector elements in the detector array.

56. The apparatus of claim 44 wherein the quality control apparatus is part of an on-line monitoring apparatus that continuously monitors a moving process web.

57. The apparatus of claim 56 wherein the quality control apparatus is operative to detect product defects that include non-uniformity of a size of capsules transported by the web.

58. The apparatus of claim 44 wherein the quality control apparatus is operative to detect product defects that include contamination or damage.

59. The apparatus of claim 44 wherein the quality control apparatus is operative to detect product defects that include product non-uniformity.

60. The apparatus of claim 44 wherein the mapping module is a color mapping module.

61. The apparatus of claim 44 further including an additional processor operative to evaluate the different areas, the additional processor having an input responsive to the mapping module and an output for providing information about the areas.

62. The apparatus of claim 44 wherein the spectral processor is operative to perform univariate spectral manipulations on a spectral data set acquired from the array sensor.

63. The apparatus of claim 44 wherein the spectral processor is operative to perform multivariate spectral manipulations on a spectral data set acquired from the array sensor.

64. The apparatus of claim 44 wherein the spectrally selective element includes a system that simultaneously projects a plurality of spectrally-discrete versions of a same image onto the array sensor.

65. A quality control apparatus for a pharmaceutical composition, comprising:

means for acquiring a two-dimensional spectral data set expressing the response of areas of a surface to different wavelengths of radiation, and

means for mapping the spectral data set to an image including different areas that correspond to different components of the pharmaceutical composition having differing responses to different wavelengths.

66. The apparatus of claim 65 wherein the means for acquiring includes means for selecting spectral components of radiation received from ingredients of the pharmaceutical composition.

67. The apparatus of claim 65 wherein the means for processing includes means for comparing spectral signatures from a library of known spectral signatures with spectral information acquired in the step of acquiring.

68. A quality control method for a pharmaceutical composition, comprising:

acquiring a spectral data set expressing the response of areas of a surface to different wavelengths of radiation, and

mapping the spectral data set to a color image including differently colored areas that correspond to different ones of the parts of surface having differing responses to the different wavelengths.

69. The method of claim 68 further including the step of comparing spectral signatures from a library of known spectral signatures including signatures for one or more components of the pharmaceutical composition.