In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy

A. L. Fussell, E. T. Garbacik, K. Löbmann, H. L. Offerhaus, P. Kleinebudde, Clare J. Strachan

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

Abstract

A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compacts surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compacts surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.

Original languageEnglish
Title of host publicationMultiphoton Microscopy in the Biomedical Sciences XIV
PublisherSPIE
Volume8948
ISBN (Print)9780819498618
DOIs
Publication statusPublished - 28 Feb 2014
EventSPIE BiOS 2014: International Biomedical Optics and Biophotonics Conference - San Francisco, United States
Duration: 2 Feb 20144 Feb 2014

Conference

ConferenceSPIE BiOS 2014
Abbreviated titleBiOS
CountryUnited States
CitySan Francisco
Period2/02/144/02/14
OtherPart of SPIE Photonics West 2014

Fingerprint

Raman Spectrum Analysis
Dosage Forms
Drug products
Theophylline
Raman scattering
Microscopy
Microscopic examination
dissolving
Dissolution
Raman spectra
microscopy
dosage
Pharmaceutical Preparations
Crystallization
Optical parametric oscillators
Naproxen
Cimetidine
parametric amplifiers
solid state
Crystal growth

Keywords

  • carbamazepine
  • cimetidine
  • Coherent anti-Stokes Raman scattering
  • dissolution
  • hyperspectral imaging
  • microscopy
  • naproxen
  • pharmaceutics
  • theophylline

Cite this

Fussell, A. L., Garbacik, E. T., Löbmann, K., Offerhaus, H. L., Kleinebudde, P., & Strachan, C. J. (2014). In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy. In Multiphoton Microscopy in the Biomedical Sciences XIV (Vol. 8948). [89482J] SPIE. https://doi.org/10.1117/12.2038933
Fussell, A. L. ; Garbacik, E. T. ; Löbmann, K. ; Offerhaus, H. L. ; Kleinebudde, P. ; Strachan, Clare J. / In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy. Multiphoton Microscopy in the Biomedical Sciences XIV. Vol. 8948 SPIE, 2014.
@inproceedings{14cba1528cd644bc9ead81681b0fe792,
title = "In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy",
abstract = "A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compacts surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compacts surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.",
keywords = "carbamazepine, cimetidine, Coherent anti-Stokes Raman scattering, dissolution, hyperspectral imaging, microscopy, naproxen, pharmaceutics, theophylline",
author = "Fussell, {A. L.} and Garbacik, {E. T.} and K. L{\"o}bmann and Offerhaus, {H. L.} and P. Kleinebudde and Strachan, {Clare J.}",
year = "2014",
month = "2",
day = "28",
doi = "10.1117/12.2038933",
language = "English",
isbn = "9780819498618",
volume = "8948",
booktitle = "Multiphoton Microscopy in the Biomedical Sciences XIV",
publisher = "SPIE",
address = "United States",

}

Fussell, AL, Garbacik, ET, Löbmann, K, Offerhaus, HL, Kleinebudde, P & Strachan, CJ 2014, In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy. in Multiphoton Microscopy in the Biomedical Sciences XIV. vol. 8948, 89482J, SPIE, SPIE BiOS 2014, San Francisco, United States, 2/02/14. https://doi.org/10.1117/12.2038933

In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy. / Fussell, A. L.; Garbacik, E. T.; Löbmann, K.; Offerhaus, H. L.; Kleinebudde, P.; Strachan, Clare J.

Multiphoton Microscopy in the Biomedical Sciences XIV. Vol. 8948 SPIE, 2014. 89482J.

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

TY - GEN

T1 - In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy

AU - Fussell, A. L.

AU - Garbacik, E. T.

AU - Löbmann, K.

AU - Offerhaus, H. L.

AU - Kleinebudde, P.

AU - Strachan, Clare J.

PY - 2014/2/28

Y1 - 2014/2/28

N2 - A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compacts surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compacts surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.

AB - A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compacts surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compacts surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.

KW - carbamazepine

KW - cimetidine

KW - Coherent anti-Stokes Raman scattering

KW - dissolution

KW - hyperspectral imaging

KW - microscopy

KW - naproxen

KW - pharmaceutics

KW - theophylline

UR - http://www.scopus.com/inward/record.url?scp=84898047937&partnerID=8YFLogxK

U2 - 10.1117/12.2038933

DO - 10.1117/12.2038933

M3 - Conference contribution

SN - 9780819498618

VL - 8948

BT - Multiphoton Microscopy in the Biomedical Sciences XIV

PB - SPIE

ER -

Fussell AL, Garbacik ET, Löbmann K, Offerhaus HL, Kleinebudde P, Strachan CJ. In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy. In Multiphoton Microscopy in the Biomedical Sciences XIV. Vol. 8948. SPIE. 2014. 89482J https://doi.org/10.1117/12.2038933