WO2009156468A1 - Procédé d’analyse d’un échantillon pharmaceutique - Google Patents

Procédé d’analyse d’un échantillon pharmaceutique Download PDF

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Publication number
WO2009156468A1
WO2009156468A1 PCT/EP2009/057963 EP2009057963W WO2009156468A1 WO 2009156468 A1 WO2009156468 A1 WO 2009156468A1 EP 2009057963 W EP2009057963 W EP 2009057963W WO 2009156468 A1 WO2009156468 A1 WO 2009156468A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical
sample
pharmaceutical sample
production line
samples
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Application number
PCT/EP2009/057963
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English (en)
Inventor
Roger Stuart Hutton
Original Assignee
Glaxo Group Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited
Publication of WO2009156468A1 publication Critical patent/WO2009156468A1/fr

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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
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/88—Investigating the presence of flaws or contamination
    • G01N21/95—Investigating the presence of flaws or contamination characterised by the material or shape of the object to be examined
    • G01N21/9508—Capsules; Tablets
    • 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
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
    • 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
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3581—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation

Definitions

  • the present invention relates to a method for determining characteristics of a pharmaceutical sample by means of a pulse of illumination addressed thereat
  • the method is suitable for determining the dimensions, density and/or content uniformity of a pharmaceutical sample.
  • NIR near infrared
  • io Raman spectroscopy Known chemical analysis methods including near infrared (NIR) spectroscopy and io Raman spectroscopy have been described for use in the imaging of pharmaceutical solid dosage forms.
  • NIR near infrared
  • io Raman spectroscopy is for example, described in G.
  • the Applicant has now devised a new method for investigating and analysing the properties, particularly the uniformity of a pharmaceutical sample.
  • the present method can be used to rapidly determine the dimensions, density and/or the content uniformity of a pharmaceutical sample and can be used to analyse materials on a continuous production line.
  • the present method is particularly applicable to determinations involving pharmaceutical solid dosage forms (e.g. tablets and powder-filled blisters and capsules)
  • the present method enables analysis measurements to be made very rapidly such that potentially 100 % of all pharmaceutical samples can be analysed on a production line.
  • the method herein may also be used in measuring and controlling pharmaceutical powder dispensing (e.g. loading powder into a blister pack or capsule), where accuracy of dispensing can be a particular problem.
  • the present method involves illuminating the pharmaceutical sample within an optical cavity with a pulse of a beam (e.g. a broad beam) of electromagnetic radiation which could be in the THz part of the spectrum and measuring the transmission and/or reflection characteristics of the beam For an optical cavity of known dimensions, such measurement can then be used to obtain the thickness and/or weight of the pharmaceutical sample.
  • a pulse of a beam e.g. a broad beam
  • electromagnetic radiation which could be in the THz part of the spectrum
  • the use of an electromagnetic beam provides a simple and convenient method to illuminate a pharmaceutical sample.
  • the present method measurement is inherently fast (e.g. of the order of femto seconds) and may therefore be used for continuous monitoring of a production line.
  • Advantages of the present method include its suitability for use in the inspection and analysis of potentially 100% of pharmaceutical materials on a production line without the need for any sample removal or any robotics sampling associated therewith.
  • the present method incorporates short illumination pulse, and additional illumination is not required.
  • the present method is conducted using electromagnetic radiation in other parts of the spectrum (e.g. visible, NIR or microwave).
  • electromagnetic radiation in other parts of the spectrum
  • light scattering dominates and it is not possible to measure the dimensions of the pharmaceutical sample.
  • For a powder form pharmaceutical sample light scattering is affected by the particle size distribution.
  • measurements in the visible, NIR and microwave parts of the spectrum can be used as a measure of the particle size distribution of the pharmaceutical powder sample.
  • the method in particular enables the analysis of the thickness, weight, density and content uniformity of the pharmaceutical sample.
  • the pharmaceutical sample is a pharmaceutical solid dosage form such as a tablet or a capsule form.
  • the pharmaceutical sample is in the form of a powder or suspension.
  • the pharmaceutical sample is a pharmaceutical dosage form within packaging (e.g. powdered medicament in a capsule or a blister pack).
  • the method can be used to analyse the thickness and/or density and/or content uniformity of powders or suspensions (e.g. of medicament products, such as inhalable medicament products).
  • the present method may be conducted using electromagnetic radiation in non-THz parts of the spectrum (e.g. visible, NIR or microwave).
  • electromagnetic radiation in non-THz parts of the spectrum
  • NIR near-IR
  • microwave microwave
  • light scattering dominates and it is not possible to measure the dimensions of the pharmaceutical sample.
  • light scattering is affected by the particle size distribution and such measurements in the visible, NIR and microwave parts of the spectrum can therefore be used as a measure of the particle size distribution of the pharmaceutical powder sample.
  • the method involves the step of identifying a pharmaceutical sample for analysis.
  • the identification of the pharmaceutical sample is required only in order that the sample may be placed within an optical cavity and that a pulse of a beam of electromagnetic radiation may be suitably directed or aligned with the pharmaceutical sample.
  • the identification may involve identifying the pharmaceutical sample pathway on the production line, again for suitable direction or aligning of the beam.
  • the identifying step may involve the identification of a particular point of interest on the pharmaceutical sample, which point of interest may in embodiments, comprise all of the pharmaceutical sample (i e. the whole pharmaceutical sample)
  • the method then involves placing said pharmaceutical sample within an optical cavity of known cavity width.
  • the optical cavity is established between a source of the electromagnetic beam and an optical mirror.
  • the pharmaceutical sample is then placed between that source and optical mirror.
  • the optical mirror is defined by a mirrored surface of a packaging container (e.g. a wall of a blister pack) into which the pharmaceutical sample is introduced. Where the pharmaceutical sample is one of many on a production line, the optical cavity is therefore established at a suitable point on the production line.
  • the method involves the step of illuminating the pharmaceutical sample with a pulse (that is to say, at least one pulse) of a beam of electromagnetic radiation.
  • the width of the beam is selected in part by reference to the pharmaceutical sample and of any point of interest thereon.
  • the beam width is comparable to one or more dimensions of the pharmaceutical sample itself.
  • the optimal beam width will be determined by what features are to be measured and the effect of surface curvature Beam width may be controlled by optical set-up of the detecting apparatus including for example, focus point, and optical F-number etc.
  • the exact beam width for a particular pharmaceutical sample type would be determined by investigation.
  • the width of the broad beam is comparable (e.g. approximately equal to) to that of a dimension of interest (e.g. width, length, diameter) of the pharmaceutical sample, which may in embodiments be the maximum dimension thereof.
  • the width of the broad beam is typically from 0 to 200%, particularly from 10 to 150%, such as from 80 to 120% of the relevant dimension (e g the maximum dimension) of the pharmaceutical sample.
  • the beam may itself have a beam width of from 1 mm to up to 20mm, particularly from 3mm to 15mm, such as from 8 to 12mm
  • Such broad beam width compares to the narrow beams used in 3D-mapp ⁇ ng methods, in which narrowly-focused beams are employed. In other embodiments herein, a more narrowly-focused beam is employed.
  • the width of the broad beam is selected such that the whole of a position of interest on the pharmaceutical sample is illuminated thereby.
  • that position of interest corresponds to the whole area of the pharmaceutical sample that is accessible to illumination, that is to say the whole of an area of a pharmaceutical sample that may be illuminated by addressing a broad beam of electromagnetic radiation thereat, and which thus, does not lie in the shadow of that broad beam.
  • a narrower beam is employed such that only part of a position of interest on the pharmaceutical sample is illuminated.
  • the pulse is of electromagnetic radiation.
  • the properties of the pulse including pulse width and pulse intensity may be selected by reference to the pharmaceutical sample to be analysed.
  • the electromagnetic radiation is selected to have a suitable wavelength.
  • the wavelength is in the visible, near infra red (NIR), microwave or Terahertz (THz) part of the spectrum.
  • NIR near infra red
  • THz microwave radiation
  • THz microwave radiation
  • THz microwave radiation
  • the beam of electromagnetic radiation is an infrared pulse at 800 nm of pulse width 100 fs such as with a repetition rate of 80 MHz.
  • the method involves detecting at least one property of the beam subsequent to illuminating the pharmaceutical sample.
  • the property of the beam may be selected according to the analytical detail required. Suitable examples of properties that may be detected (i.e. measured) include beam reflectance, transmission and scattering.
  • One particular property that may be detected is the time delay of the reflected, transmitted or scattered beam.
  • the source of illumination of the pharmaceutical sample is generally a point source.
  • the detector may in embodiments, be either a point source detector or an array detector (e.g. an array of detectors).
  • the present method can involve detection of reflected and transmitted light.
  • an image of the surface is not generated.
  • Source and detector need therefore not be collinear relative to each other, and the position of each will determine whether information on scattering, reflectance and transmission is obtained.
  • the method involves referencing the measured at least one property (e.g. time delay) of the beam subsequent to illumination of the pharmaceutical sample and also the known cavity width of the optical cavity to derive structural information relating to that pharmaceutical sample.
  • this reference involves computerised analysis (e.g. by graphical representation or by reference to look-up tables) of the measured at least one property of the beam.
  • the pharmaceutical sample is illuminated with the electromagnetic beam and the transmission and/or reflection of that beam is monitored.
  • the reflected and/or transmitted beam contains information on variations in refractive index of the pharmaceutical sample and/or of the thickness of the pharmaceutical sample.
  • measurement of the speed of light in the pharmaceutical sample may be employed to derive information relating to that pharmaceutical sample.
  • the measurable time delay is given by the expression:
  • d is the thickness of the pharmaceutical sample and ⁇ the refractive index thereof
  • ⁇ is linked to changes in sample density and is also related as follows:
  • the method herein employs the use of an optical cavity to independently measure ⁇ and d for the pharmaceutical sample.
  • the thickness of the pharmaceutical sample can be independently determined wherein:
  • Thickness of pharmaceutical sample cavity width - (time for light transit through air x speed of light).
  • the refractive index and thickness of the pharmaceutical sample can be independently determined
  • the refractive index and thickness of the pharmaceutical sample is used to determine the content uniformity (CU) and/or the density of the pharmaceutical sample.
  • this is a rapid non destructive measurement that can in embodiments be used for real time analysis of pharmaceutical products (e.g. tablets and powder-filled blisters and capsules).
  • the method herein can be used to measure the Content Uniformity (CU) of the pharmaceutical sample.
  • the pharmaceutical sample is comprised of both active pharmaceutical ingredient (API) and excipient and the Content Uniformity relates principally to the uniformity of the ratio of API: excipient throughout the pharmaceutical sample. It will be appreciated that the density of such a pharmaceutical sample will also be indicative of the ratio of API. excipient.
  • the method provides the means to rapidly determine tablet CU and could be used for 100% tablet inspection
  • active pharmaceutical ingredient (API) powder is placed into a capsule or blister pack, optionally also with excipient
  • the method herein could be used to measure the powder density and dimensions.
  • the powder density and dimensions can be used to measure the amount of API in the capsule or blister pack.
  • Measurements in the THz part of the spectrum are not significantly affected by scattering effects.
  • such THz measurements can be used to measure the depth/thickness of powders and the density variations related to their packing.
  • measurements of depth and density can be used to measure content uniformity within dry powder inhalers (DPI).
  • a broad beam of electromagnetic radiation may be employed.
  • the use of a broad beam of electromagnetic radiation for analysis of the structure of the pharmaceutical sample means that mapping of the pharmaceutical sample ( ⁇ e using multiple point readings using a narrowly focused beam) is not required.
  • mapping of the pharmaceutical sample ⁇ e using multiple point readings using a narrowly focused beam
  • the present method is inherently fast and may therefore be used for continuous monitoring of a production line such as in the context of 'on production line' analysis for real time release of products.
  • each pharmaceutical sample of the plural pharmaceutical samples on the production line is presented in series and hence, the method is applied sequentially (i.e. along the series) to each pharmaceutical sample of the plural pharmaceutical samples. In embodiments, the method is repeated for each pharmaceutical sample (e g. at a particular point on the production line). In another aspect, the method is applied to two or more of said pharmaceutical samples of the plural pharmaceutical samples at a time.
  • the illuminating step is synchronised with the movement (e.g. speed of presentation) of pharmaceutical samples (at an illuminating station) on a production line. That is to say, in embodiments the step of illuminating each pharmaceutical sample of the plural pharmaceutical samples is synchronised with the movement of the plural pharmaceutical samples on the production line.
  • the method herein is conducted in situ as the pharmaceutical samples move on the production line itself ('on line analysis'). That is to say, a measuring station necessary for carrying out the method is located for analysis of the pharmaceutical samples as they pass along the production itself.
  • the pharmaceutical samples are diverted from the production line to a measuring station spaced therefrom, but typically at a convenient position local thereto ('at line analysis'). That is to say, the apparatus necessary for carrying out the method is arranged for analysis of at least some of the pharmaceutical samples at a position diverted from the production line, but typically local thereto.
  • the measuring station e.g. an analyser
  • the measuring station locates adjacent to a tablet press.
  • Figure 1 a shows a schematic representation of an instrumental set-up suitable for carrying out a method of the present invention in calibration mode
  • Figure 1 b shows a schematic representation of the instrumental set-up of Figure 1 a now in sample analysis mode
  • Figure 2a shows typical reflected traces obtained for a pulse of a beam of electromagnetic radiation during calibration using the instrumentation set-up of Figure 1a;
  • Figure 2b shows typical reflected traces obtained for a pulse of a beam of electromagnetic radiation applied to a tablet pharmaceutical sample using the instrumentation set-up of Figure 1 b;
  • Figure 3a shows a representative instrumentation set up for transmission measurements
  • Figure 3b shows a representative instrumentation set up for scattering measurements
  • Figure 4 shows a schematic representation of a production line set-up arranged for carrying out the method of the present invention
  • Figure 5 shows a perspective view of the form of a drug pack of a form suitable for containing powder medicament for analysis in accord with the present invention
  • Figure 6 shows a top view of the form of the drug pack of Figure 4.
  • Figure 7 shows a representative instrumentation set for conducting analysis of the filling of a blister pack with a pharmaceutical powder
  • Figure 8 shows typical reflected traces obtained for a pulse of a beam of electromagnetic radiation applied to a blister pack with a pharmaceutical powder using the instrumentation set-up of Figure 7.
  • Figures 1a and 1 b show a schematic representation of an instrumental set-up suitable for carrying out a reflectance-based method herein, as shown respectively in calibration and sample analysis modes.
  • Figures 2a and 2b show representative traces of time delay (in mm) versus THz waveform obtainable using the respective instrumentation set ups of Figures 1a and 1 b.
  • both Figures 1 a and 1 b shows an experimental configuration, in which THZ generator 10 is employed to generate at least one THz pulse 12 that is arranged for reflectance by mirror 30 and later for detection by THz detector 20.
  • the THz generator 10 and reflector 20 are housed within the same body.
  • the space between THz generator 10, THz detector 20 and mirror 30 may be understood to comprise an optical cavity, the optical width of which may be readily determined.
  • an ultra short pulse laser may be provided to the THz generator 10 to allow for generation of a THz pulse 12.
  • the ultra short pulse laser apparatus may for example comprise a Ti: sapphire, Yb: Er doped fibre, Cr: LiSAF, Yb: silica, Nd : YLF, Nd: Glass, Nd : YAG or Alexandrite type of laser.
  • the physical width of the beam may be varied according to the size characteristics of the pharmaceutical sample, but typically comprises from 0 to 100% of the maximum dimension of the pharmaceutical sample. The beam width determines the area (and hence volume) of pharmaceutical sample 50 that is interrogated. In the case that the complete pharmaceutical sample 50 is illuminated and information on the entire pharmaceutical sample is obtainable.
  • Beam 1 which reflects off the leading face 52 of the sample 50
  • Beam 2 which reflects off the trailing face 54 of the sample 50
  • Beam 3 which reflects from the mirror 30
  • Structural information is obtainable by measuring t-i , t 2 and t 3 and using the expressions:
  • c va cuum speed of light in vacuum
  • c sa mpie speed of light in sample
  • d caV ⁇ ty cavity length
  • d sa m P ⁇ e sample length
  • t cav ⁇ ty time to traverse cavity.
  • dsampie and Csampie can be experimentally determined and also: Csampie ⁇ refractive index sa mpie ⁇ density sa mpie
  • FIG. 3a shows a representative instrumentation set up for transmission measurements
  • Figure 3b shows a representative instrumentation set up for scattering measurements.
  • THZ generator 10 is employed to generate at least one THz pulse 12 that is arranged for detection by THz detector 20 after transmission/scattering by a pharmaceutical sample 50.
  • FIG. 4 shows a representative production line set up arranged for this purpose.
  • Belt 105 carries pharmaceutical samples 150 (e.g. tablet pharmaceutical samples) along a forward direction 107.
  • pharmaceutical samples 150 e.g. tablet pharmaceutical samples
  • an optical cavity is established in the space defined between THz generator 1 10, THz detector 120 and mirror 130.
  • the pharmaceutical sample 150 is subjected at the measuring station 155 to a pulse of a beam of THz electromagnetic radiation 112 originating from THz generator 1 10.
  • Reflected THz radiation is detected by the detector 120, which sends reflectance data to computer 160 for analysis.
  • the computer 160 typically includes a monitor and graphical user interface for display and monitoring of the data by an operative.
  • the computer 160 might also be configured to monitor and analyse the data and then automatically produce control signals (e.g. error signals or production line control signals) based on such analysis.
  • control signals e.g. error signals or production line control signals
  • the computer might make reference to look-up tables or other data analysis algorithms, and such analysis may involve minimal or no user intervention.
  • the THz generator 110 and detector 120 are both also controllable by the computer to enable different variations of the method and hence, different sets of data (e.g. repeat data) to be collected.
  • the method herein is suitable for use in analysing the filling of a blister pack form drug carrier with a powder form medicament.
  • Figure 5 shows a representative blister form drug pack 270 comprising a flexible strip 271 defining a plurality of pockets 273, 275, 277 each of which would contain a portion of a dose of 5 drug in the form of powder, which can be inhaled.
  • the strip 270 comprises a base sheet 279 in which blisters are formed to define the pockets 273, 275, 277 and a lid sheet 281 which is hermetically sealed to the base sheet except in the region of the blisters in such a manner that the lid sheet 281 and the base sheet 279 can be peeled apart.
  • the sheets 279, 281 are sealed to one another over their whole width io except for the leading end portions 283, 285 where they are preferably not sealed to one another at all.
  • the lid 281 and base 279 sheets are formed of a laminate and are suitably adhered to one another by heat sealing.
  • the strip 271 is shown as having elongate pockets 273, 275, and 277 that run transversely with respect to the length of the strip 271. This is convenient in that it enables a large number of pockets 273,
  • the strip 271 may, for example, be provided with sixty or one hundred pockets but it will be understood that the strip 271 may have any suitable number of pockets.
  • Each blister 273, 275, 277 may be seen to have a length h that is preferably from 1.5 to 15.0 mm, more preferably, from 1.5 to 8.0 mm, and in an actual embodiment is equal to 7.5 mm, measured along its longer axis, and a width I 2 that is preferably from 1.5 to 10.0 mm, more preferably, from 1.5 to 8.0 mm, and in an actual embodiment is equal to 4.0 mm, measured along its shorter axis.
  • 25 blisters 273, 275, 277 are typically at 7.5 mm spacing along the blister strip 270.
  • Each blister 273, 275, 277 contains an effective dosage of powder, preferably less than 30 mg of powder, more preferably, between 5 - 25 mg of powder, and most preferably, approximately 12.5 mg of powder.
  • the powder is suitably an inhalable drug composition comprising at least one drug active.
  • Filling of a drug pack of the type shown in Figures 5 and 6 may be carried out by any suitable process including those described in US Patent No. 5,187,921 ; PCT Patent Application No. WO 00/71419; and US Patent Application No. US2005/ 118,260, the contents of all of which are incorporated herein by reference.
  • the method herein is used to determine the weight of powder filled into each blister pocket 273, 275, 277 during filling thereof on a production line.
  • medicament powder filled into the blister strip 270 is typically approx. 99% inhalation grade lactose, blended with the active pharmaceutical ingredient (API).
  • Standard dose is 13mg.
  • Environmental conditions during manufacture and filling are maintained at 18 - 22 0 C, 35 - 60% RH.
  • the target mean fill weight is 13 mg and the target standard deviation is less than 0.3 mg.
  • Difference in fill weight may arise from dispensing variations due to losses in transfer process and from variations in powder properties, density and flowability.
  • the method herein enables the powder density and dimensions to be determined, this in turn can and hence, Content Uniformity. Use of the method herein can be used to provide 100% testing of pockets on-line.
  • Figure 7 show a schematic representation of an instrumental set-up suitable for carrying out a reflectance-based method herein, for analysis of the filling of a pocket 273 of a blister pack 270 with pharmaceutical powder 250.
  • Figure 8 shows a representative trace of time delay (in mm) versus THz waveform obtainable using the instrumentation set up of Figure 8.
  • Figure 7 shows an experimental configuration, in which THZ generator 210 is employed to generate at least one THz pulse 212 that is arranged for reflectance by a mirror surface provided by the inner wall 230 of the blister pocket 273 of a blister pack 270 and later for detection by THz detector 220.
  • the THz generator 210 and reflector 220 are housed within the same body.
  • the space between THz generator 210, THz detector 220 and the reflecting inner wall 230 of the blister pocket 273 may be understood to comprise an optical cavity, the optical width of which may be readily determined.
  • a pharmaceutical powder sample 250 defining a top surface 252 has now been introduced into the blister pocket 273.
  • Beam 1 which reflects off the top surface 252 of the powder sample 250 2.
  • Beam 2 which reflects from the inner wall 230 of the blister pocket 273
  • Structural information is obtainable by measuring ti and t 2 and using the expressions:

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  • Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
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  • Toxicology (AREA)
  • Investigating Materials By The Use Of Optical Means Adapted For Particular Applications (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

La présente invention concerne un procédé d’analyse d’un échantillon pharmaceutique (150) qui comprend l’identification d’un échantillon pharmaceutique (150) ; le positionnement de l’échantillon pharmaceutique (150) à l’intérieur d’une cavité optique (155) ayant une largeur de cavité connue ; l’illumination de l’échantillon pharmaceutique (150) avec une impulsion d’un faisceau (112) de rayonnement électromagnétique ; la détection (120) d’au moins une propriété dudit faisceau (112) après l’illumination de l’échantillon pharmaceutique (150) ; et le référencement de la ou des propriétés du faisceau (112) et de ladite largeur de cavité connue pour dériver des informations structurelles relatives à l’échantillon pharmaceutique (150). Le procédé est adapté pour être utilisé dans l’analyse continue des échantillons pharmaceutiques (150) sur une ligne de production (105).
PCT/EP2009/057963 2008-06-26 2009-06-25 Procédé d’analyse d’un échantillon pharmaceutique WO2009156468A1 (fr)

Applications Claiming Priority (2)

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GB0811742A GB0811742D0 (en) 2008-06-26 2008-06-26 Method for analysis of a pharmaceutical sample
GB0811742.6 2008-06-26

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WO2010133335A1 (fr) * 2009-05-19 2010-11-25 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Procédé pour déterminer une quantité d'une substance fluide qui est ajoutée de façon dosée dans un corps à remplir
WO2014078290A3 (fr) * 2012-11-13 2014-07-10 R. J. Reynolds Tobacco Company Système d'analyse d'un filtre d'article à fumer associé à un article à fumer et procédé associé
GB2527416A (en) * 2014-05-08 2015-12-23 Advantest Corp Dynamic Measurement of density using terahertz radiation with real-time thickness measurement for process control
EP2863211A4 (fr) * 2012-06-18 2016-06-15 Nipro Corp Dispositif de détection d'impuretés dans une poudre utilisant des ondes pulsées térahertz et procédé de détection d'impuretés
US9606054B2 (en) 2013-09-30 2017-03-28 Advantest Corporation Methods, sampling device and apparatus for terahertz imaging and spectroscopy of coated beads, particles and/or microparticles
WO2020104011A1 (fr) 2018-11-19 2020-05-28 Tera Group Ag Procédé et dispositif de classification d'un échantillon au moyen d'une spectroscopie térahertz
CN111868506A (zh) * 2018-03-14 2020-10-30 Ckd株式会社 检查装置、ptp包装机与检查方法

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