Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
  • G01N21/47—Scattering, i.e. diffuse reflection
  • G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
  • G01N21/51—Scattering, i.e. diffuse reflection within a body or fluid inside a container, e.g. in an ampoule
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
  • G01N15/02—Investigating particle size or size distribution
  • G01N15/0205—Investigating particle size or size distribution by optical means
  • G01N15/0211—Investigating a scatter or diffraction pattern
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
  • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
  • G01J3/28—Investigating the spectrum
  • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
  • G01J3/4412—Scattering spectrometry
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
  • G01N2015/0096—Investigating consistence of powders, dustability, dustiness
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
  • G01N15/02—Investigating particle size or size distribution
  • G01N15/0205—Investigating particle size or size distribution by optical means
  • G01N15/0211—Investigating a scatter or diffraction pattern
  • G01N2015/0216—Investigating a scatter or diffraction pattern from fluctuations of diffraction pattern
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
  • G01N15/02—Investigating particle size or size distribution
  • G01N15/0205—Investigating particle size or size distribution by optical means
  • G01N15/0211—Investigating a scatter or diffraction pattern
  • G01N2015/0222—Investigating a scatter or diffraction pattern from dynamic light scattering, e.g. photon correlation spectroscopy
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
  • G01N21/47—Scattering, i.e. diffuse reflection
  • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
  • G01N2021/4797—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium time resolved, e.g. analysis of ballistic photons
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/84—Systems specially adapted for particular applications
  • G01N21/85—Investigating moving fluids or granular solids
  • G01N2021/8592—Grain or other flowing solid samples

Definitions

• the amplitude of scattered light 4 may be attenuated relative to incident light 3.
• An amplitude attenuation module 12 of measurement module 6 measures the amplitude attenuation of scattered light 4.
• the average intensity of the modulated signal module 12b of measurement module 6 measures the average intensity DC d of the modulated signal.
• Optical property module 8 determines optical properties of powder bed P according to the phase shift, amplitude attenuation, and average intensity of the modulated signal using a model of light propagation within the powder. Optical properties may include an absorption coefficient, powder anisotropy, and scattering coefficient.
• An absorption coefficient module 13 determines the absorption coefficient
• a scattering coefficient module 14a determines the scattering coefficient
• a scattering anisotropy module 14b determines the mean cosine of scattering from the powder.
• FDPM frequency- domain photon migration
• FIGURE 4 is a block diagram illustrating another embodiment of light source 530.
• Light source 530 may comprise a continuous wave (CW) laser 537 that generates a beam 538.
• Beam 538 is focused into an acousto-optic modulator 539 that is driven by a radio frequency (RF) signal at frequency ⁇ produced by a frequency synthesizer 534.
• the RF signal results in an intensity modulated beam 536 from acousto-optic modulator 539 at the same frequency.
• CW continuous wave
• RF radio frequency
• Processor 562 receives signals from reference detector 549 and sample detector 554 via an analog-to-digital converter 570.
• Analog-to-digital converter 570 may comprise a data acquisition module suitable for digitizing output from reference detector 549 and sample detector 554.
• Processor 562 may send a control signal to frequency synthesizers 534 and 563 to change the values of ⁇ and ⁇ + ⁇ in tandem.
• processor 562 may provide output to change the position of detector fiber 552 relative to the position of source fiber 546, or accept signals from one of a number of sample detectors 554 replicated to measure FDPM parameters as a function of distance 2p, away from the incident point source of light.
• Controller 116 may be implemented using Schmitt triggers.
• a Schmitt trigger may be used as an oscillator to generate a calibration time base.
• One-shot circuits use Schmitt triggers to generate two consecutive pulses in accordance with the calibration time base, which are used to calibrate bias and write pulse signals.
• Controller 116 supplies the modulation signal to laser source 112 in accordance with the write pulse signal. The modulation signal is not supplied while the bias and write calibration is taking place, so a circuit may be used to insert the proper levels to the modulation signal during the calibration.
• Laser source module 110 and laser source 112 operate as a source that provides photons that interact with a powder.
• An interface 140 comprising analog-to-digital converters 142 converts analog signals from detector module 130 to digital signals.
• a processor 150 processes information from the signals to determine characteristics of powder bed P. Processor 150 may determine the characteristics according to the methods described with reference to FIGURES 12 and 13.
• the measurements may be analyzed using fast Fourier transforms to recover the phase delay and amplitude attenuation of the modulation at each light source wavelength.
• the phase shift ⁇ , amplitude attenuation I AC , and average intensity of the modulated signal DC are measured at each location i at step 308.
• the measurements may be made as a function of the separation p between the source fiber and detector fiber, the modulation frequency ⁇ , or both.
• Optical properties such as abso ⁇ tion coefficient ⁇ a and isotropic scattering coefficient ⁇ ' s are determined from phase shift ⁇ , amplitude attenuation I AC , and average intensity DC at step 310.
• Abso ⁇ tion coefficient ⁇ ⁇ indicates the ability of a substance to absorb light of a particular wavelength
• the isotropic scattering coefficient ⁇ ' s indicates the ability of a substance to scatter light of a particular wavelength.
• FIGURE 13 is a flowchart illustrating one embodiment of a method for computing powder characteristics.
• the method may be used to calculate characteristics such as the uniformity of an ingredient, the uniformity of particle size, the volume of powder sampled, or any combination of the preceding.
• the method begins at step 700, where abso ⁇ tion coefficient ⁇ a and isotropic scattering coefficient ⁇ ' s are determined from the diffusion approximation or another approximation to the radiative transport equation.
• Equation (13) The relationship defining the cumulative probability at a prolate spherical radius ⁇ within the powder bed is given by Equations (13):
• FIGURE 14 is a diagram 800 describing example measurements of dimensionless absorbance [ ⁇ ⁇ ( ⁇ ) - ⁇ ° ( ⁇ )]/ ⁇ ° ( ⁇ ) versus active pharmaceutical ingredient (API) concentration by percent weight of a Terazosin powder mixture at wavelengths of 514 nm ( ⁇ ), 650 nm ( ⁇ ), 687 nm ( ⁇ ), and 785 nm (0).
• the components of the excipient powder are assumed to be well mixed and may be represented by a constant absorbance.
• Symbols 802 ⁇ , ⁇ , *- , and 0 denote experimental measurements
• lines 804 denote the linear fit.
• the slope of each line 804 provides an extinction coefficient associated with the wavelength of the line 804.
• the wavelength of light that is absorbed maximally by the active pharmaceutical ingredient possesses the highest extinction coefficient and gives rise to the highest sensitivity to changes in the active pharmaceutical ingredients.
• FIGURE 17 is a diagram 830 illustrating example FDPM measurements of the scattering coefficient of a powder bed as a function of particle size.
• Diagram 830 provides an example of the relationship between measurements of isotropic scattering performed by the method of FIGURE 13 and the reciprocal of the mean powder particle size at 828, 785, and 650 nanometers. At 650 nanometers, the wavelength of light becomes comparable to the particle sizes interrogated and exhibits a different constant factor ⁇ .
• the relative standard deviation of concentration describes the standard deviation normalized against a nominal target dose concentration.
• the sampled volume may be used to determine if measurement variances are sufficiently small to assess content uniformity.
• CCM complete- random-mixture
• the complete- random-mixture (CRM) model used to describe powder blends shows that the variance associated with measurement of discretely sampled powders is inversely proportional to the sampled volume in the case of a completely mixed sample. Consequently, the amount of sampled volume dictates the smallest measurement variance for a statistical evaluation of blend uniformity.
• NIR Near infrared

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• Chemical & Material Sciences (AREA)
• Physics & Mathematics (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Analytical Chemistry (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Dispersion Chemistry (AREA)
• Investigating Or Analysing Materials By Optical Means (AREA)

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• 2002
  • 2002-10-21 US US10/274,790 patent/US6771370B2/en not_active Expired - Lifetime
  • 2002-10-22 WO PCT/US2002/033900 patent/WO2003036275A2/en not_active Ceased
  • 2002-10-22 EP EP02791188A patent/EP1438569A2/en not_active Withdrawn
  • 2002-10-22 JP JP2003538724A patent/JP2005519261A/ja active Pending
  • 2002-10-22 AU AU2002363068A patent/AU2002363068A1/en not_active Abandoned

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