Role of excipients in the quantification of water in lyophilised mixtures using NIR spectroscopy

Grohganz, Holger; Fonteyne, Margot; Skibsted, Erik; Falck, Thomas; Palmqvist, Bent; Rantanen, Jukka

doi:10.1016/j.jpba.2009.01.021

Cited by 31 publications

(27 citation statements)

References 19 publications

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“…This is the core idea of the PAT framework (3). Near infrared (NIR) spectroscopy has traditionally been used as the preferred analytical method when incorporating the PAT initiative (6)(7)(8). The reasons for the success of NIR spectroscopy include the absence of sample preparation, fast analysis time, as well as noninvasive and nondestructive sample analysis (9,10).…”

Section: Introductionmentioning

confidence: 99%

Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy

Maltesen

Weert

2012

AAPS PharmSciTech

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Abstract. Moisture content and aerodynamic particle size are critical quality attributes for spray-dried protein formulations. In this study, spray-dried insulin powders intended for pulmonary delivery were produced applying design of experiments methodology. Near infrared spectroscopy (NIR) in combination with preprocessing and multivariate analysis in the form of partial least squares projections to latent structures (PLS) were used to correlate the spectral data with moisture content and aerodynamic particle size measured by a time of flight principle. PLS models predicting the moisture content were based on the chemical information of the water molecules in the NIR spectrum. Models yielded prediction errors (RMSEP) between 0.39% and 0.48% with thermal gravimetric analysis used as reference method. The PLS models predicting the aerodynamic particle size were based on baseline offset in the NIR spectra and yielded prediction errors between 0.27 and 0.48 μm. The morphology of the spray-dried particles had a significant impact on the predictive ability of the models. Good predictive models could be obtained for spherical particles with a calibration error (RMSECV) of 0.22 μm, whereas wrinkled particles resulted in much less robust models with a Q 2 of 0.69. Based on the results in this study, NIR is a suitable tool for process analysis of the spray-drying process and for control of moisture content and particle size, in particular for smooth and spherical particles.

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Section: Introductionmentioning

confidence: 99%

Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy

Maltesen

Weert

2012

AAPS PharmSciTech

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“…The PLS provided satisfactory results of linear regression between the NIR and the KF method with   of 0.98 and RMSECV of 0.15 % appropriately. Similarly, Grohganz et al (2009) also demonstrated a NIR technique for quantification of water in freeze-dried lyophilized mixtures and showed good model accuracy with a low error. Muzzio et al (2011) used NIR combined with PCR and PLS analysis for the prediction of water contents in lyophilized mannitol (mannitol was used as an excipient in lyophilized pharmaceutical products).…”

Section: Moisture Contentmentioning

confidence: 88%

“…In this process, the water in the samples is removed by sublimation under vacuum; hence, monitoring the correct moisture content is important during the drying process. Grohganz et al (2009) investigated water content (determined by the KF titration method) of freeze-dried mannitol-sucrose excipients using NIR spectroscopy (1250-2500 nm). The PLS provided satisfactory results of linear regression between the NIR and the KF method with   of 0.98 and RMSECV of 0.15 % appropriately.…”

Section: Moisture Contentmentioning

confidence: 99%

Spectroscopic Techniques for Nondestructive Quality Inspection of Pharmaceutical Products: A Review

Kandpal

Park

Tewari

et al. 2015

Journal of Biosystems Engineering

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Spectroscopy is an emerging technology for the quality assessment of pharmaceutical samples, from tablet manufacturing to final quality assurance. The traditional methods for the quality management of pharmaceutical tablets are time consuming and destructive, while spectroscopic techniques allow rapid analysis in a non-destructive manner. The advantage of spectroscopy is that it collects both spatial and spectral information (called hyperspectral imaging), which is useful for the chemical imaging of pharmaceutical samples. These chemical images provide both qualitative and quantitative information on tablet samples. In the pharmaceutics, spectroscopic techniques are used for a variety of applications, such as analysis of the homogeneity of powder samples as well as determination of particle size, product composition, and the concentration, uniformity, and distribution of the active pharmaceutical ingredient in solid tablets. This review paper presents an introduction to the applications of various spectroscopic techniques such as hyperspectroscopy and vibrational spectroscopies (Raman spectroscopy, FT-NIR, and IR spectroscopy) for the quality and safety assessment of pharmaceutical solid dosage forms. In addition, various chemometric techniques that are highly essential for analyzing the spectroscopic data of pharmaceutical samples are also reviewed.

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“…In the PCA analysis of the NIR spectra, a standard normal variate (SNV) transformation was used to reduce the variation caused by the physical characteristics (29). Based on previous experience, the PLS regression was performed on untreated spectra, standard normal variate spectra and second derivate spectra (30). In all cases, the spectra were centred prior to analysis regardless of the pre-treatment method, while no other scaling (such as univariate scaling) was applied.…”

Section: Multivariate Data Analysismentioning

confidence: 99%

“…To overcome this variation, different transformations of the spectral data set were evaluated. A SNV transformation has been used in NIR spectroscopy to reduce the variation in the baseline offset (25,30). However, for the FTIR spectra, the obtained models contain the same number of principal components and did not explain more of the data compared with models based on raw spectral data.…”

Section: Multivariate Analyses Of Ftir Spectramentioning

confidence: 99%

Multivariate Analysis of Phenol in Freeze-Dried and Spray-Dried Insulin Formulations by NIR and FTIR

et al. 2011

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Dehydration is a commonly used method to stabilise protein formulations. Upon dehydration, there is a significant risk the composition of the formulation will change especially if the protein formulation contains volatile compounds. Phenol is often used as excipient in insulin formulations, stabilising the insulin hexamer by changing the secondary structure. We have previously shown that it is possible to maintain this structural change after drying. The aim of this study was to evaluate the residual phenol content in spray-dried and freeze-dried insulin formulations by Fourier transform infrared (FTIR) spectroscopy and near infrared (NIR) spectroscopy using multivariate data analysis. A principal component analysis (PCA) and partial least squares (PLS) projections were used to analyse spectral data. After drying, there was a difference between the two drying methods in the phenol/insulin ratio and the water content of the dried samples. The spray-dried samples contained more water and less phenol compared with the freeze-dried samples. For the FTIR spectra, the best model used one PLS component to describe the phenol/insulin ratio in the powders, and was based on the second derivative pre-treated spectra in the 850-650 cm −1 region. The best PLS model based on the NIR spectra utilised three PLS components to describe the phenol/insulin ratio and was based on the standard normal variate transformed spectra in the 6,200-5,800 cm −1 region. The root mean square error of cross validation was 0.69% and 0.60% (w/w) for the models based on the FTIR and NIR spectra, respectively. In general, both methods were suitable for phenol quantification in dried phenol/insulin samples.

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Role of excipients in the quantification of water in lyophilised mixtures using NIR spectroscopy

Cited by 31 publications

References 19 publications

Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy

Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy

Spectroscopic Techniques for Nondestructive Quality Inspection of Pharmaceutical Products: A Review

Multivariate Analysis of Phenol in Freeze-Dried and Spray-Dried Insulin Formulations by NIR and FTIR

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