Raman spectroscopy and multivariate analysis for the rapid discrimination between native-like and non-native states in freeze-dried protein formulations

As the number of applications for polymers in pharmaceutical development is increasing, there is need for fundamental understanding on how such compounds behave during tableting. This research is focussed on the tableting behaviour of amorphous polymers, their solid dispersions and the impact of hot-melt extrusion on the compaction properties of these materials. Soluplus, Kollidon VA 64 and Eudragit EPO were selected as amorphous polymers since these are widely studied carriers for solid dispersions, while Celecoxib was chosen as BCS class II model drug. Neat polymers and physical mixtures (up to 35% drug load) were processed by hot-melt extrusion (HME), milled and sieved to obtain powders with comparable particle sizes as the neat polymer. A novel approach was used for in-line analysis of the compaction properties on a rotary tablet press (Modul P, GEA) using complementary sensors and software (CDAAS, GEA). By combining 'in-die' and 'out-of-die' techniques, it was possible to investigate in a comprehensive way the impact of HME on the tableting behaviour of amorphous polymers and their formulations. The formation of stable glassy solutions altered the formulations towards more fragmentary behaviour under compression which was beneficial for the tabletability.Principal component analysis (PCA) was applied to summarize the behaviour during compaction of the formulations, enabling the selection of Soluplus and Kollidon VA 64 as the most favourable polymers for compaction of glassy solutions.

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“…PCA is a multivariate projection method which extracts and displays the variation in the data set (Pieters et al, 2013). …”

Section: Multivariate Data Analysismentioning

confidence: 99%

In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions

Grymonpré

Verstraete

Bockstal

et al. 2017

International Journal of Pharmaceutics

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“…As a result, an increment was observed for the Raman intensity of b-sheet structures in the amide III region, while the intensities decreased for helical structures. 27 Deamidation of proteins is another process which can be easily followed by using Raman spectroscopy. Amide bands and amino acid residue bands were monitored to detect the changes.…”

Section: Proteinsmentioning

confidence: 99%

Dispersive and FT-Raman spectroscopic methods in food analysis

et al. 2015

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Raman spectroscopy is a powerful technique for molecular analysis of food samples. A fingerprint spectrum can be obtained for a target molecule by using Raman technology, as specific signals are obtained for chemical bonds in the target. In this way, food components, additives, processes and changes during shelf life, adulterations and numerous contaminants such as microorganisms, chemicals and toxins, can also be determined with or without the help of chemometric methods. The studies included in this review show that Raman spectroscopy has great potential for food analyses. In this review, we aim to bring together Raman studies on components, contaminants, raw materials, and adulterations of various food, and attempt to prepare a database of Raman bands obtained from food samples.

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“…50 It aims to maximize the ratio of between-class variance to within-class variance. [51][52][53][54] A five-class LDA model was chosen. Four classes assigned to specific tissue structures (i.e., [1] normal glomeruli and tubular sections, [2] constitutive collagen, [3] fibrosis, and [4] inflammation) were retained.…”

Section: Spectral Data Processingmentioning

confidence: 99%

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

Vuiblet

Fere

Gobinet

et al. 2015

JASN

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Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier-transform infrared (FTIR) imaging-based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with .90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIRbased analysis of renal graft biopsy specimens is a reproducible and reliable label-free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.

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Raman spectroscopy and multivariate analysis for the rapid discrimination between native-like and non-native states in freeze-dried protein formulations

Cited by 38 publications

References 41 publications

In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions

In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions

Dispersive and FT-Raman spectroscopic methods in food analysis

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

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