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

Abstract

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.

Traceability of Active Compounds of Essential Oils in Antimicrobial Food Packaging Using a Chemometric Method by ATR-FTIR

“…analyze the spectra is an important step in spectroscopy. The most commonly used multivariate calibration methods are partial least squares (PLS) [29] [30] [31] and principal components (PCA) [32]. The success of these methods depends upon the choice of proper spectral data and the number of variables employed in the calibration model.…”

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

“…Several studies have investigated the particle size in various processes (6,8,28,(30)(31)(32)(33) and the moisture content of lyophilized sugars and proteins by NIR (7,8,30,(34)(35)(36). However, NIR has seldom been applied to monitor the spray-drying process, and has rarely been used when proteins are the model system (37). In addition, NIR has so far not been correlated with aerodynamic particle size; however, this should be possible as both NIR scattering and aerodynamic particle size are related to geometric particle size, density and morphology.…”

Quality by Design for Biopharmaceutical Drug Product Development

“…c. Bai et al (2005) used PLS to compare NIR and Fourier transform infrared (FTIR) spectroscopy for monitoring structural changes in lyophilized protein formulations. d. Maltesen et al (2011) used multivariate analysis 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. PCA and PLS projections were used to analyze spectral data.…”