Coherent anti-Stokes Raman scattering microscopy for pharmaceutics: a shift in the right direction

A.L. Fussell

Research output: ThesisPhD Thesis - Research UT, graduation UT

Abstract

This dissertation demonstrates coherent anti-Stokes Raman scattering (CARS) microscopy as a tool in pharmaceutical solid state development. CARS microscopy is a nonlinear optical imaging technique that uses inelastic scattering of light to provide chemically specific imaging. CARS microscopy is suitable for early stage pharmaceutical development, analyzing pure API powders as well as late stage analysis of more complex dosage forms. The strengths and weaknesses of CARS microscopy are explored in the context of pharmaceutical analysis over a wide range of samples covering a number of commonly used pharmaceutical formulation strategies. Chapter one is an introduction to the area of traditional pharmaceutical solid state analysis and provides a background to the area of CARS microscopy. Chapter two introduces and discusses hyperspectral CARS microscopy as a tool for determining pharmaceutical solid state form capable of distinguishing between hydrous and anhydrous polymorphic forms as well as between crystalline and amorphous forms. Chapter three presents CARS and hyperspectral CARS as a tool for dissolution analysis capable of correlating visualized changes on the surface of a dosage form with changes observed in the dissolution rate. Chapter three begins with details about the design and building of the dissolution setup and is followed by results obtained from a number of theophylline containing oral dosage forms. Chapter four introduces the area of inhalation medicine and looks at the capabilities of CARS microscopy to provide useful information about the formulation strategy known as adhesive mixtures. The chapter begins with analyzing drug distribution followed by particle size calculations and ends with correlative imaging combining CARS with scanning electron microscopy (SEM). Chapter five looks at a drug loaded mesoporous silica particles, which is a formulation strategy aimed at stabilizing the amorphous form of poorly water soluble drugs. CARS and hyperspectral CARS were utilized to firstly identify the three dimensional drug distribution of the loaded silica particles and secondly to confirm the amorphous nature of the loaded drug. Finally more correlative CARS and SEM imaging was performed to confirm that the loaded drug was contained within the pores of the silica.
LanguageEnglish
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • Herek, Jennifer Lynn, Supervisor
  • Offerhaus, Herman L., Advisor
  • Strachan, C.J., Advisor
Award date4 Jul 2014
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-3671-4
DOIs
StatePublished - 4 Jul 2014

Fingerprint

Raman scattering
Microscopic examination
Pharmaceutical Preparations
Dosage Forms
Silicon Dioxide
Imaging techniques
Dissolution
Direction compound
Scanning electron microscopy
Inelastic scattering
Theophylline
Application programming interfaces (API)
Powders
Medicine
Adhesives
Particle size
Crystalline materials
Water

Keywords

  • METIS-304138
  • IR-91338

Cite this

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abstract = "This dissertation demonstrates coherent anti-Stokes Raman scattering (CARS) microscopy as a tool in pharmaceutical solid state development. CARS microscopy is a nonlinear optical imaging technique that uses inelastic scattering of light to provide chemically specific imaging. CARS microscopy is suitable for early stage pharmaceutical development, analyzing pure API powders as well as late stage analysis of more complex dosage forms. The strengths and weaknesses of CARS microscopy are explored in the context of pharmaceutical analysis over a wide range of samples covering a number of commonly used pharmaceutical formulation strategies. Chapter one is an introduction to the area of traditional pharmaceutical solid state analysis and provides a background to the area of CARS microscopy. Chapter two introduces and discusses hyperspectral CARS microscopy as a tool for determining pharmaceutical solid state form capable of distinguishing between hydrous and anhydrous polymorphic forms as well as between crystalline and amorphous forms. Chapter three presents CARS and hyperspectral CARS as a tool for dissolution analysis capable of correlating visualized changes on the surface of a dosage form with changes observed in the dissolution rate. Chapter three begins with details about the design and building of the dissolution setup and is followed by results obtained from a number of theophylline containing oral dosage forms. Chapter four introduces the area of inhalation medicine and looks at the capabilities of CARS microscopy to provide useful information about the formulation strategy known as adhesive mixtures. The chapter begins with analyzing drug distribution followed by particle size calculations and ends with correlative imaging combining CARS with scanning electron microscopy (SEM). Chapter five looks at a drug loaded mesoporous silica particles, which is a formulation strategy aimed at stabilizing the amorphous form of poorly water soluble drugs. CARS and hyperspectral CARS were utilized to firstly identify the three dimensional drug distribution of the loaded silica particles and secondly to confirm the amorphous nature of the loaded drug. Finally more correlative CARS and SEM imaging was performed to confirm that the loaded drug was contained within the pores of the silica.",
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Coherent anti-Stokes Raman scattering microscopy for pharmaceutics: a shift in the right direction. / Fussell, A.L.

Enschede : Universiteit Twente, 2014. 124 p.

Research output: ThesisPhD Thesis - Research UT, graduation UT

TY - THES

T1 - Coherent anti-Stokes Raman scattering microscopy for pharmaceutics: a shift in the right direction

AU - Fussell,A.L.

PY - 2014/7/4

Y1 - 2014/7/4

N2 - This dissertation demonstrates coherent anti-Stokes Raman scattering (CARS) microscopy as a tool in pharmaceutical solid state development. CARS microscopy is a nonlinear optical imaging technique that uses inelastic scattering of light to provide chemically specific imaging. CARS microscopy is suitable for early stage pharmaceutical development, analyzing pure API powders as well as late stage analysis of more complex dosage forms. The strengths and weaknesses of CARS microscopy are explored in the context of pharmaceutical analysis over a wide range of samples covering a number of commonly used pharmaceutical formulation strategies. Chapter one is an introduction to the area of traditional pharmaceutical solid state analysis and provides a background to the area of CARS microscopy. Chapter two introduces and discusses hyperspectral CARS microscopy as a tool for determining pharmaceutical solid state form capable of distinguishing between hydrous and anhydrous polymorphic forms as well as between crystalline and amorphous forms. Chapter three presents CARS and hyperspectral CARS as a tool for dissolution analysis capable of correlating visualized changes on the surface of a dosage form with changes observed in the dissolution rate. Chapter three begins with details about the design and building of the dissolution setup and is followed by results obtained from a number of theophylline containing oral dosage forms. Chapter four introduces the area of inhalation medicine and looks at the capabilities of CARS microscopy to provide useful information about the formulation strategy known as adhesive mixtures. The chapter begins with analyzing drug distribution followed by particle size calculations and ends with correlative imaging combining CARS with scanning electron microscopy (SEM). Chapter five looks at a drug loaded mesoporous silica particles, which is a formulation strategy aimed at stabilizing the amorphous form of poorly water soluble drugs. CARS and hyperspectral CARS were utilized to firstly identify the three dimensional drug distribution of the loaded silica particles and secondly to confirm the amorphous nature of the loaded drug. Finally more correlative CARS and SEM imaging was performed to confirm that the loaded drug was contained within the pores of the silica.

AB - This dissertation demonstrates coherent anti-Stokes Raman scattering (CARS) microscopy as a tool in pharmaceutical solid state development. CARS microscopy is a nonlinear optical imaging technique that uses inelastic scattering of light to provide chemically specific imaging. CARS microscopy is suitable for early stage pharmaceutical development, analyzing pure API powders as well as late stage analysis of more complex dosage forms. The strengths and weaknesses of CARS microscopy are explored in the context of pharmaceutical analysis over a wide range of samples covering a number of commonly used pharmaceutical formulation strategies. Chapter one is an introduction to the area of traditional pharmaceutical solid state analysis and provides a background to the area of CARS microscopy. Chapter two introduces and discusses hyperspectral CARS microscopy as a tool for determining pharmaceutical solid state form capable of distinguishing between hydrous and anhydrous polymorphic forms as well as between crystalline and amorphous forms. Chapter three presents CARS and hyperspectral CARS as a tool for dissolution analysis capable of correlating visualized changes on the surface of a dosage form with changes observed in the dissolution rate. Chapter three begins with details about the design and building of the dissolution setup and is followed by results obtained from a number of theophylline containing oral dosage forms. Chapter four introduces the area of inhalation medicine and looks at the capabilities of CARS microscopy to provide useful information about the formulation strategy known as adhesive mixtures. The chapter begins with analyzing drug distribution followed by particle size calculations and ends with correlative imaging combining CARS with scanning electron microscopy (SEM). Chapter five looks at a drug loaded mesoporous silica particles, which is a formulation strategy aimed at stabilizing the amorphous form of poorly water soluble drugs. CARS and hyperspectral CARS were utilized to firstly identify the three dimensional drug distribution of the loaded silica particles and secondly to confirm the amorphous nature of the loaded drug. Finally more correlative CARS and SEM imaging was performed to confirm that the loaded drug was contained within the pores of the silica.

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KW - IR-91338

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M3 - PhD Thesis - Research UT, graduation UT

SN - 978-90-365-3671-4

PB - Universiteit Twente

CY - Enschede

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