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Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy.
Eur J Pharm Biopharm. 2010 Nov; 76(3):498-506.EJ

Abstract

X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in α-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from α-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 μm and 20 μm in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the α-lactose monohydrate granules formulated with the different grades of PVP.

Authors+Show Affiliations

Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, Nottingham, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20801216

Citation

Crean, Barry, et al. "Elucidation of the Internal Physical and Chemical Microstructure of Pharmaceutical Granules Using X-ray Micro-computed Tomography, Raman Microscopy and Infrared Spectroscopy." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 76, no. 3, 2010, pp. 498-506.
Crean B, Parker A, Roux DL, et al. Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy. Eur J Pharm Biopharm. 2010;76(3):498-506.
Crean, B., Parker, A., Roux, D. L., Perkins, M., Luk, S. Y., Banks, S. R., Melia, C. D., & Roberts, C. J. (2010). Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 76(3), 498-506. https://doi.org/10.1016/j.ejpb.2010.08.006
Crean B, et al. Elucidation of the Internal Physical and Chemical Microstructure of Pharmaceutical Granules Using X-ray Micro-computed Tomography, Raman Microscopy and Infrared Spectroscopy. Eur J Pharm Biopharm. 2010;76(3):498-506. PubMed PMID: 20801216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy. AU - Crean,Barry, AU - Parker,Andrew, AU - Roux,Delphine Le, AU - Perkins,Mark, AU - Luk,Shen Y, AU - Banks,Simon R, AU - Melia,Colin D, AU - Roberts,Clive J, Y1 - 2010/08/27/ PY - 2010/05/03/received PY - 2010/08/05/revised PY - 2010/08/22/accepted PY - 2010/8/31/entrez PY - 2010/8/31/pubmed PY - 2011/5/27/medline SP - 498 EP - 506 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 76 IS - 3 N2 - X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in α-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from α-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 μm and 20 μm in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the α-lactose monohydrate granules formulated with the different grades of PVP. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/20801216/Elucidation_of_the_internal_physical_and_chemical_microstructure_of_pharmaceutical_granules_using_X_ray_micro_computed_tomography_Raman_microscopy_and_infrared_spectroscopy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(10)00216-X DB - PRIME DP - Unbound Medicine ER -