Raman analysis

• US 8,085,396 B2
• Filed: 04/05/2007
• Issued: 12/27/2011
• Est. Priority Date: 04/05/2006
• Status: Active Grant

• Current Assignee: Agilent Technologies Lda Uk Limited (Agilent Technologies, Inc.)
• Original Assignee: Science and Technology Facilities Council
• Inventors: Matousek, Pavel, Parker, Anthony William
• Primary Examiner(s): Toatley, Gregory J
• Assistant Examiner(s): ALLI, IYABO
• Application Number:
  US12/083,073
• Publication Number:
  US 20090244533A1
• Time in Patent Office: 1,727 Days
• Field of Search: 250/341.2, 250/338.1, 250/215, 250/221, 250/573, 250/339.07, 250/339.11, 356/300, 356/301, 356/326, 356/328, 3562371-2374, 359/613, 359/539, 359/296
• US Class Current: 356/301
• CPC Class Codes: A61B 5/417 the bone marrow
• CPC Class Codes: G01N 2021/656 Raman microprobe
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G07D 7/1205 Testing spectral properties

Abstract

Properties of turbid or scattering samples are determined using Raman spectroscopy with probe light delivered to and subsequently collected from the sample using a transmission geometry. The technique may be applied to pharmaceutical products such as tablets, diagnostic tests such as lateral flow diagnostic strips, and elsewhere.

Claims

1. A method of determining one or more properties of a pharmaceutical dosage formulation, the method comprising:

exposing a first surface of said formulation to incident radiation;

receiving, from a second surface of said formulation spaced from said first surface, elements of said incident radiation forward scattered through said formulation from said first surface to said second surface;

detecting Raman scattered spectral elements in said received radiation; and

determining one or more of said properties from said detected Raman scattered elements,

wherein said pharmaceutical dosage formulation is diffusely scattering of said incident radiation between said first and second surfaces.

2. The method of claim 1 wherein said second surface is on an opposite side of said dosage formulation to said first surface.

3. The method of claim 1 further comprising collecting backscattered elements of said incident radiation, and detecting Raman scattered spectral elements in said backscattered element.

4. The method of claim 1 wherein said dosage formulation is retained in a carrier having one or more inner surfaces facing said dosage formulation, at least a portion of the inner surfaces being mirrored so as to reflect escaping radiation back into said dosage formulation.

5. The method of claim 4 wherein said carrier comprises a first aperture through which the first surface of said dosage formulation is exposed to said incident radiation, and a second aperture through which the forward scattered elements are received from the second surface of said dosage formulation.

6. The method of claim 5 wherein said incident radiation is generated using one or more lasers.

7. A method of testing a plurality of pharmaceutical dosage formulations comprising applying the steps of claim 1 to each of the dosage formulations.

8. The method of claim 1 wherein said pharmaceutical dosage formulation is selected from a list comprising:

a tablet;

a capsule;

a coated tablet;

a gelcap; and

a packaged pharmaceutical product .

9. The method of claim 1 wherein the pharmaceutical dosage formulation comprises a turbid solid object .

10. The method of claim 1 wherein said one or more properties include one or more of a polymorph form property, a hydrated form property, a solvate form property, a salt form property, and a degree of crystallinity property.

11. The method of claim 1 wherein said one or more properties include one or more indications of starting materials used in chemical reactions to form a component of said dosage formulation.

25. The method of claim 1, wherein the pharmaceutical dosage formulation is a coated tablet, a capsule or a gelcap, and the one or more properties are properties of an interior portion of the coated tablet, capsule or gelcap.

26. The method of claim 1, wherein the pharmaceutical dosage formulation is a tablet or capsule in a blister pack.

29. The method of claim 1, wherein the method is a method of analysing the bulk of a pharmaceutical dosage formulation.

32. A method of production of a plurality of pharmaceutical dosage formulations, the method comprising:

carrying out the steps of claim 1 on each formulation; and

for each formulation, analysing the detected Raman radiation to determine one or more characteristics of each formulation.

33. The method of claim 32, further comprising rejecting one or more of the formulations on the basis of the one or more determined characteristics.

12. A method of analysing the bulk of a pharmaceutical dosage formulation comprising

directing incident radiation at said dosage formulation and

detecting Raman radiation scattered in the dosage formulation using a transmission geometry,

wherein said pharmaceutical dosage formulation is diffusely scattering of said incident radiation.

13. Apparatus for analysing a pharmaceutical dosage formulation, comprising:

a carrier for retaining a dosage formulation;

illumination optics arranged to direct incident radiation to a first surface of a said formulation;

reception optics arranged to receive, from a second surface of said formulation spaced from said first surface, elements of said incident radiation forward scattered from said first surface through said formulation to said second surface, and to detect Raman scattered spectral elements in said received radiation,

wherein said dosage formulation is diffusely scattering of said incident radiation between said first and second surfaces.

14. The apparatus of claim 13 wherein said reception optics comprise a spectral analyser arranged to detect one or more of said Raman spectral elements of said received elements of radiation.

15. The apparatus of claim 13 wherein said reception optics comprises one or more spectral filters arranged to isolate one or more of said Raman spectral elements of said received elements of radiation for detection.

16. The apparatus of claims 13 further comprising an analyser arranged to derive one or more properties of said dosage formulation from said Raman scattered spectral elements.

17. The apparatus of claim 16 wherein the one or more properties which the analyser is arranged to derive include one or more of a polymorph form property, a hydrated form property, a solvate form property, a salt form property, and a degree of crystallinity property.

18. The apparatus of claim 16 wherein said one or more properties which the analyser is arranged to derive include one or more indications of starting materials used in chemical reactions to form a component of said dosage formulation.

19. The apparatus of claim 13 wherein said second surface is on an opposite side of said dosage formulation to said first surface.

20. The apparatus of claim 13 wherein said carrier has one or more inner surfaces facing said dosage formulation and at least a portion of the inner surfaces is mirrored so as to reflect radiation back into said dosage formulation.

21. The apparatus of claim 13 wherein said carrier comprises a first aperture through which the first surface of said dosage formulation is exposed to said incident radiation, and a second aperture through which forward scattered elements of the incident radiation are received from the second surface of said dosage formulation.

22. The apparatus of claim 13 further comprising a laser source arranged to generate said incident radiation.

23. A facility for testing a plurality of pharmaceutical dosage formulations comprising the apparatus of claim 13.

24. The apparatus of claim 13 wherein said pharmaceutical dosage formulation is selected from a list comprising:

a tablet;

a capsule;

a coated tablet;

a gelcap; and

a packaged pharmaceutical product.

27. The apparatus of claim 13, wherein the pharmaceutical dosage formulation is a coated tablet, a capsule or a gelcap, and the one or more properties are properties of an interior portion of the coated tablet, capsule or gelcap.

28. The apparatus of claim 13, wherein the pharmaceutical dosage formulation is a tablet or capsule in a blister pack.

30. The apparatus of claim 13, wherein the apparatus is an apparatus for analysing the hulk of a pharmaceutical dosage formulation.

31. The apparatus of claim 13, further comprising at least one of said pharmaceutical dosage formulation arranged for analysis.