# US 7,745,789 B2 · Measuring technique > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,789 B2 - Document ID: US7745789B2 - Status: Granted - Kind: B2 - Application number: 11/457,606 - Filed: 2006-07-14 - Published: 2006-11-02 - Granted: 2010-06-29 - Earliest claimed: 2001-03-21 - Assignees: AstraZeneca AB - Inventors: Christoffer Abrahamsson; Stefan Andersson-Engels; Staffan Folestad; Jonas Johansson; Sune Svanberg - Web page: https://patentgrep.com/patent/US7745789B2 ## CPC - G01N 21/3563: for analysing solids; Preparation of samples therefor - G01N 21/359: using near infrared light - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The present invention relates to apparatuses for use in performing a quantitative analysis of a turbid pharmaceutical sample, e.g. a tablet, a capsule or a similar sample forming a pharmaceutical dose. A pharmaceutical, turbid sample (24, 57, 67) is irradiated with an excitation beam (20, 53, 64) of radiation, e.g. near infrared radiation. The intensity of emitted radiation (30) from the sample (24, 57, 67) is detected as function of both the wavelength of the emitted radiation and the photon propagation time through said sample (24, 57, 67). Optionally, the intensity of the emitted radiation (30) from the sample (24, 57, 67) is also detected in a spatially resolved manner. ## Claims ### Claim 1 An apparatus for quantitative analysis of a turbid pharmaceutical sample, comprising: means for generating an excitation beam of radiation; means for intensity modulating said excitation beam; means for focusing said excitation beam onto said sample, said means being parts of a Fourier spectrometer; and means for detecting all wavelengths simultaneously, and for measuring the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 2 (depends on 1) An apparatus as claimed in claim 1, wherein said means for detecting comprises a time-resolved detection unit. ### Claim 3 (depends on 1) An apparatus as claimed in claim 1, wherein said means for detecting comprises a phase-resolved detection unit. ### Claim 4 (depends on 1) An apparatus as claimed in claim 1, wherein said means for detecting comprises a time-gated system. ### Claim 5 (depends on 1) An apparatus as claimed in claim 1, further comprising means for performing a spatial-resolved detection of said intensity. ### Claim 6 (depends on 1) An apparatus as claimed in claim 1, wherein said pharmaceutical, turbid sample is a solid sample, in particular a tablet, a capsule, a bulk powder or an equivalent pharmaceutical dose. ### Claim 7 (depends on 1) An apparatus as claimed in claim 1, wherein said pharmaceutical, turbid sample is a dispersion. ### Claim 8 (depends on 1) An apparatus as claimed in claim 1, wherein the excitation beam comprises infrared radiation. ### Claim 9 (depends on 8) An apparatus as claimed in claim 8, wherein the infrared radiation is in the near infrared radiation (NIR). ### Claim 10 (depends on 1) An apparatus as claimed in claim 1, wherein the radiation has a frequency in the range corresponding to wavelengths from 700 to 1700 nm. ### Claim 11 (depends on 1) An apparatus as claimed in claim 1, wherein the excitation beam comprises visible light. ### Claim 12 (depends on 1) An apparatus as claimed in claim 1, wherein the excitation beam comprises UV radiation. ### Claim 13 (depends on 1) An apparatus as claimed in claim 1, wherein said means for generating an excitation beam of radiation comprises one or more diode lasers. ### Claim 14 (depends on 1) An apparatus as claimed in claim 1, wherein said means for generating an excitation beam of radiation comprises an intensity modulated lamp. ### Claim 15 (depends on 1) An apparatus as claimed in claim 1, wherein said means for generating an excitation beam of radiation comprises an intensity modulated light emitting diode (LED). ### Claim 16 (depends on 1) An apparatus as claimed in claim 1, wherein said means for intensity modulating said excitation beam is a modulation driver. ### Claim 17 (depends on 16) An apparatus as claimed in claim 16, wherein a phase comparator is arranged to compare signals from the modulation driver and from the detector. ### Claim 18 (depends on 1) An apparatus as claimed in claim 1, comprising means for positioning a turbid pharmaceutical sample. ### Claim 19 An apparatus for quantitative analysis of a turbid pharmaceutical sample, comprising: means for generating an excitation beam of radiation; means for focusing said excitation beam onto said sample; means for splitting said excitation beam into two beams; and means for detecting transmitted light and non-transmitted light respectively, comprising a time-resolved detection unit, and for measuring the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 20 (depends on 19) An apparatus as claimed in claim 19, wherein said means for detecting comprises a phase-resolved detection unit. ### Claim 21 (depends on 19) An apparatus as claimed in claim 19, wherein said means for detecting comprises a time-gated system. ### Claim 22 (depends on 19) An apparatus as claimed in claim 19, further comprising means for performing a spatial-resolved detection of said intensity. ### Claim 23 (depends on 19) An apparatus as claimed in claim 19, wherein said pharmaceutical, turbid sample is a solid sample, in particular a tablet, a capsule, a bulk powder or an equivalent pharmaceutical dose. ### Claim 24 (depends on 19) An apparatus as claimed in claim 19, wherein said pharmaceutical, turbid sample is a dispersion. ### Claim 25 (depends on 19) An apparatus as claimed in claim 19, wherein the excitation beam comprises infrared radiation. ### Claim 26 (depends on 25) An apparatus as claimed in claim 25, wherein the infrared radiation is in the near infrared radiation (NIR). ### Claim 27 (depends on 19) An apparatus as claimed in claim 19, wherein the radiation has a frequency in the range corresponding to wavelengths from 700 to 1700 nm. ### Claim 28 (depends on 19) An apparatus as claimed in claim 19, wherein the excitation beam comprises visible light. ### Claim 29 (depends on 19) An apparatus as claimed in claim 19, wherein the excitation beam comprises UV radiation. ### Claim 30 (depends on 19) An apparatus as claimed in any claim 19, wherein said means for generating an excitation beam of radiation comprises one or more diode lasers. ### Claim 31 (depends on 19) An apparatus as claimed in claim 19, wherein said means for generating an excitation beam of radiation comprises an intensity modulated lamp. ### Claim 32 (depends on 19) An apparatus as claimed in claim 19, wherein said means for generating an excitation beam of radiation comprises an intensity modulated light emitting diode (LED). ### Claim 33 (depends on 19) An apparatus as claimed in claim 19, wherein said means for generating an excitation beam of radiation is an array of diode lasers and a multiplexer. ### Claim 34 (depends on 19) An apparatus as claimed in claim 19, wherein said means for detecting transmitted light and non-transmitted light are photomultipliers. ### Claim 35 (depends on 19) An apparatus as claimed in claim 19, wherein a phase comparator is arranged to compare the signals from said means for detecting transmitted light and non-transmitted light. ### Claim 36 An apparatus for quantitative analysis of a turbid pharmaceutical sample, comprising: means for generating an excitation beam of radiation; means for focusing said excitation beam onto said sample; means for splitting said excitation beam into two beams; and means for detecting transmitted light and non-transmitted light respectively, comprising a phase-resolved detection unit, and for measuring the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 37 A method for quantitative analysis of a turbid pharmaceutical sample, comprising: (a) generating an excitation beam of radiation; (b) intensity modulating the excitation beam; (c) focusing the excitation beam onto the sample; (d) detecting all wavelengths simultaneously; and (e) measuring the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 38 (depends on 37) The method of claim 37 further comprising producing an interferogram containing information about the light transmitted through the sample at all wavelengths. ### Claim 39 A method for quantitative analysis of a turbid pharmaceutical sample, comprising: (a) generating an excitation beam of radiation; (b) focusing the excitation beam onto the sample; (c) splitting the excitation beam into two beams; (d) detecting transmitted light and non-transmitted light respectively; and (e) measuring the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 40 An apparatus for quantitative analysis of a turbid pharmaceutical sample, comprising: (a) a light source configured to emit an excitation beam; (b) a modulation driver configured to intensity modulate the light source; (c) an optical system configured to focus the excitation beam on the sample; and (d) a detector configured to monitor the light transmitted through the sample, and to measure the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 41 (depends on 40) The apparatus of claim 40 further comprising a phase comparator configured to compare a signal from the modulation driver with a signal from the detector. ### Claim 42 An apparatus for quantitative analysis of a turbid pharmaceutical sample, comprising: (a) a light source configured to emit an excitation beam; (b) a beam splitter configured to split the excitation beam into two beams, a first beam being directed towards the sample and a second beam being directed so that it will not pass through the sample; (c) a first detector configured to detect light transmitted through the sample from the first beam; and (d) a second detector configured to detect light from the second beam transmitted directly from the beam splitter to the second detector wherein each detector is also configured to measure the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons. ### Claim 43 (depends on 42) The apparatus of claim 42 further comprising a phase comparator configured to compare a signal from the first detector with a signal from the second detector. ### Claim 44 (depends on 42) The apparatus of claim 42 wherein the first and second detectors comprise photomultipliers. ### Claim 45 An apparatus for quantitative analysis of a turbid pharmaceutical sample, comprising: means for generating an excitation beam of radiation; means for intensity modulating said excitation beam; means for focusing said excitation beam onto said sample, said means being parts of a Fourier spectrometer; means for detecting all wavelengths simultaneously, and for measuring the intensity of radiation emitted from the sample both as a function of the wavelength of the emitted radiation and as a function of photon propagation time through said sample, so as to determine time delay or phase difference of scattered photons; and means for performing a spatial-resolved detection of said intensity, wherein said means for detecting comprises a phase-resolved detection unit, wherein the excitation beam comprises visible light, wherein said means for intensity modulating said excitation beam is a modulation driver.