Confocal Raman Microscopy in Pharmaceutical Development

Haefele, Thomas; Paulus, Kurt

doi:10.1007/978-3-642-12522-5_8

Cited by 4 publications

(2 citation statements)

References 105 publications

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“…Raman spectroscopy is a cost-effective, label free and non-destructive analytical tool [ 1 ] that delivers specific molecular information to enable the determination of the chemical composition of samples within seconds, with minimum or no requirements for sample preparation. The technique is based on the illumination of samples with a monochromatic laser source, resulting in a fraction of the light being inelastically scattered (the Raman effect) which can be collected as spectral signatures [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

In Situ Water Quantification in Natural Deep Eutectic Solvents Using Portable Raman Spectroscopy

et al. 2021

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Raman spectroscopy is a label-free, non-destructive, non-invasive analytical tool that provides insight into the molecular composition of samples with minimum or no sample preparation. The increased availability of commercial portable Raman devices presents a potentially easy and convenient analytical solution for day-to-day analysis in laboratories and production lines. However, their performance for highly specific and sensitive analysis applications has not been extensively evaluated. This study performs a direct comparison of such a commercially available, portable Raman system, with a research grade Raman microscope system for the analysis of water content of Natural Deep Eutectic Solvents (NADES). NADES are renewable, biodegradable and easily tunable “green” solvents, outcompeting existing organic solvents for applications in extraction from biomass, biocatalysis, and nanoparticle synthesis. Water content in NADES is, however, a critical parameter, affecting their properties, optimal use and extraction efficiency. In the present study, portable Raman spectroscopy coupled with Partial Least Squares Regression (PLSR) is investigated for rapid determination of water content in NADES samples in situ, i.e., directly in glassware. Three NADES systems, namely Betaine Glycerol (BG), Choline Chloride Glycerol (CCG) and Glucose Glycerol (GG), containing a range of water concentrations between 0% (w/w) and 28.5% (w/w), were studied. The results are directly compared with previously published studies of the same systems, using a research grade Raman microscope. PLSR results demonstrate the reliability of the analysis, surrendering R2 values above 0.99. Root Mean Square Errors Prediction (RMSEP) of 0.6805%, 0.9859% and 1.2907% w/w were found for respectively unknown CCG, BG and GG samples using the portable device compared to 0.4715%, 0.3437% and 0.7409% w/w previously obtained by analysis in quartz cuvettes with a Raman confocal microscope. Despite the relatively higher values of RMSEP observed, the comparison of the percentage of relative errors in the predicted concentration highlights that, overall, the portable device delivers accuracy below 5%. Ultimately, it has been demonstrated that portable Raman spectroscopy enables accurate quantification of water in NADES directly through glass vials without the requirement for sample withdrawal. Such compact instruments provide solvent and consumable free analysis for rapid analysis directly in laboratories and for non-expert users. Portable Raman is a promising approach for high throughput monitoring of water content in NADES that can support the development of new analytical protocols in the field of green chemistry in research and development laboratories but also in the industry as a routine quality control tool.

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Section: Introductionmentioning

confidence: 99%

In Situ Water Quantification in Natural Deep Eutectic Solvents Using Portable Raman Spectroscopy

et al. 2021

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“…Raman spectroscopy has been extensively utilized in the pharmaceutical industry to quantify drug polymorphism. 19–27 It has been demonstrated that the interactions between excipients and drug molecules can be investigated using Raman spectroscopy. 21,22,24,28,29 Raman spectroscopy is also highly amenable to high-throughput implementation, 30–32 and when used in combination with various chemometric methods and proper calibration procedures can yield accurate quantitation of various properties of interest.…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Raman Spectroscopy Screening of Excipients for the Stabilization of Amorphous Drugs

et al. 2015

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Low aqueous solubility of active pharmaceutical ingredients (APIs) is an enduring problem in pharmaceutical development, and it is becoming increasingly prevalent among new drug candidates. It is estimated that about 40% of drugs in the development pipeline and approximately 60% of the drugs coming directly from discovery suffer from poor aqueous solubility and slow dissolution, thereby reducing their bioavailability and efficacy and thus preventing their commercialization. It is well known that utilizing the amorphous form of a drug can be a useful approach to improve the dissolution rate and solubility of poorly water-soluble APIs. Amorphous compounds are thermodynamically unstable, but they can be stabilized by combining them with a carrier polymer (excipient) to form a solid dispersion. High-throughput Raman spectroscopy was used in this study to identify excipients that promote formation and stabilization of the amorphous drug form in solid dispersions. Four model APIs were used as poorly soluble drug candidates: ketoprofen, danazol, griseofulvin, and probucol. The Raman signals of excipients were generally negligible, and therefore Raman bands from the drugs were used with minimal spectral pre-processing. By comparing Raman spectra collected from the APIs in the crystalline and molten state, appropriate spectral features and regions were identified for the development of semi-quantitative methods to determine the amorphous content for each API. It is demonstrated that methods based on peak intensity ratio, peak width, peak distance, and classical least squares can all be effective methods for the screening of excipients. Interesting excipient-dependent phase transformation behavior was also observed for probucol.

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The Impact of Solid Dispersion on Formulation, Using Confocal Micro Raman Spectroscopy as Tool to Probe Distribution of Components

et al. 2017

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Confocal Raman Microscopy in Pharmaceutical Development

Cited by 4 publications

References 105 publications

In Situ Water Quantification in Natural Deep Eutectic Solvents Using Portable Raman Spectroscopy

In Situ Water Quantification in Natural Deep Eutectic Solvents Using Portable Raman Spectroscopy

High-Throughput Raman Spectroscopy Screening of Excipients for the Stabilization of Amorphous Drugs

The Impact of Solid Dispersion on Formulation, Using Confocal Micro Raman Spectroscopy as Tool to Probe Distribution of Components

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