Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy

Crean, Barry; Parker, Andrew P.; Roux, Delphine Le; Perkins, Mark C.; Luk, Shen Y.; Banks, Simon R.; Melia, Colin D.; Roberts, Clive J.

doi:10.1016/j.ejpb.2010.08.006

Cited by 36 publications

(17 citation statements)

References 34 publications

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“…It is then evidenced that the degree of porosity is influenced by the drug content within the extruded material and this is the first report of non-homogeneity in extruded materials at a micro-structural level. This is similar to reported micro-structure variations for tablets (Sinka et al, 2004), granules (Crean et al, 2010) and calendered tablets (Vynckier et al, 2015) where it was observed the influence of pores formed during coextrusion into tablet adhesion degree between core and coat. Such studies indicate that despite the known mixing ability of twin-screw processing (Crowley et al, 2007) standard techniques for assessing homogeneity may not be adequate.…”

Section: Computed Tomography (µ-Ct)supporting

confidence: 91%

“…Extruded materials were scanned using a µ-CT instrument in order to show at a micromolecular level the homogeneity properties and suitability of HME technique to obtain a high mixing degree product. Previous studies to assess drug content uniformity within HME systems incorporated a fluorescent dye (Park et al, 2013) however characterisation of materials internal structure by computed tomography (CT) has gained popularity as a useful tool to examine solid dosage forms such as tablets (Sinka et al, 2004) or granule intermediates (Crean et al, 2010) and more recently co-extruded materials (Vynckier et al, 2015). This technique offers the possibility to analyse the material's internal structure through X-rays scans and visualise density and porosity characteristics.…”

Section: Computed Tomography (µ-Ct)mentioning

confidence: 99%

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A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

Martinez-Marcos

Lamprou

McBurney

et al. 2016

International Journal of Pharmaceutics

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The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect.

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Section: Computed Tomography (µ-Ct)supporting

confidence: 91%

Section: Computed Tomography (µ-Ct)mentioning

confidence: 99%

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

Martinez-Marcos

Lamprou

McBurney

et al. 2016

International Journal of Pharmaceutics

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“…By use of X-ray μCT, pores smaller than the resolution of the measurement (approximately 6 µm in this study) could not be detected. In addition, Farber et al 16) mentioned in their report that in samples with high porosity, the original cross-sectional images have relatively low signal-to-noise ratio, which results in an uncertainty of up to 10% in porosity calculation. Since bulk sample is measured using mercury porosimetry, it is said that it cannot distinguish inter-granule voids from inner-granule voids.…”

Section: Experimental Materialsmentioning

confidence: 99%

“…Some examples of the application of X-ray μCT to the analysis of internal microstructure of granules have been reported. For example, Farber et al 16) studied porosity, pore size distribution, and geometric structure of pores in granules produced using different conditions and materials. Crean et al 17) elucidated the internal physical and chemical microstructure of pharmaceutical granules in conjunction with spectroscopic methods.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Microstructure of Granules Prepared by Continuous Twin Screw Granulator Using X-Ray Micro-computed Tomography

Matsui

Ando

Yamamoto

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Granules prepared by a continuous twin screw granulator (TSG) were analyzed by X-ray micro-computed tomography (X-ray μCT) and the relationships between porosity of granules and granule properties were investigated. A model formulation containing ibuprofen, lactose monohydrate, microcrystalline cellulose, and hydroxypropyl cellulose was used. The porosity of granules was measured by X-ray μCT and mercury porosimetry. The data sets obtained by both methods showed linear correlation despite different values, which were attributed to the resolution of X-ray μCT and a low-signal-to-noise ratio of the original cross-sectional images. The porosity of granules measured by X-ray μCT decreased from 11-14 to 6-7% as liquid-to-solid ratio (L/S) increased, while the standard deviation (S.D.) of the porosity of individual granules decreased from 4-5 to 2%. L/S affected the porosity of granules. By contrast, the effect of screw speed was not significant. Pressure transmission, G, which indicates the liquid dispersion in wet kneaded masses, increased as the porosity of granules and the S.D. decreased. The cross-sectional images showed that granules were densified as L/S increased. Based on these results, the effect of L/S on the porosity of granules can be explained by liquid dispersion and densification of the wet granules. The porosity of granules measured by X-ray μCT showed good linear correlation with friability and drug dissolution rate (R 2 0.9107 and 0.8834, respectively). This study revealed that the drug dissolution rate was regulated by a disintegration step in which the porosity of granules plays an important role.

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“…To avoid this limitation, it is possible to use correlative microscopy. Crean et al [15] and Van Dalen et al [16] have shown that using 2-D imaging methods, such as SEM-EDX, Raman microscopy, and infrared microscopy, in combination with XRμT results can improve the phase resolution. Another limitation in using XRμT is that quantitative image analysis is limited by the resolution of the instrument and the resulting quality of the obtained images.…”

Section: Introductionmentioning

confidence: 98%

Measuring granule phase volume distributions using X-ray microtomography

2014

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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

Cited by 36 publications

References 34 publications

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

Analysis of Microstructure of Granules Prepared by Continuous Twin Screw Granulator Using X-Ray Micro-computed Tomography

Measuring granule phase volume distributions using X-ray microtomography

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