The application of multiple linear regression to the measurement of the median particle size of drugs and pharmaceutical excipients by near-infrared spectroscopy

O’Neil, Andrew J.; Jee, Roger D.; Moffat, A.C.

doi:10.1039/a806001k

Cited by 60 publications

(45 citation statements)

References 19 publications

(22 reference statements)

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“…NIRS has also been successfully used in a variety of other analytical chemistry applications such as the detection of degradation products in tablets (7); studying drug moisture content over time and water mobility within the drug crystal lattice (8,9); real-time monitoring of moisture during processing using fluidized bed granulation (10,11) or roller compaction (12), measurement of particle size, and size distribution (13)(14)(15); and determining the tablet drug content and content uniformity (16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

NIR Spectroscopy Applications in the Development of a Compacted Multiparticulate System for Modified Release

et al. 2011

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Abstract. The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to characterize extrusion-spheronized drug beads, lipid-based placebo beads, and modified release tablets prepared from blends of these beads. The tablet drug load (10.5-19.5 mg) of theophylline (2.25 mg increments) and cimetidine (3 mg increments) could easily be differentiated using univariate analyses. To evaluate other tablet attributes (i.e., compression force, crushing force, content uniformity), multivariate analyses were used. Partial least squares (PLS) models were used for prediction and principal component analysis (PCA) was used for classification. The PLS prediction models (R 2 >0.98) for content uniformity of uncoated compacted theophylline and cimetidine beads produced the most robust models. Content uniformity data for tablets with drug content ranging between 10.5 and 19.5 mg showed standard error of calibration (SEC), standard error of cross-validation, and standard error of prediction (SEP) values as 0.31, 0.43, and 0.37 mg, and 0.47, 0.59, and 0.49 mg, for theophylline and cimetidine, respectively, with SEP/SEC ratios less than 1.3. PCA could detect blend segregation during tableting for preparations using different ratios of uncoated cimetidine beads to placebo beads (20:80, 50:50, and 80:20). Using NIR chemical imaging, the 80:20 formulations showed the most pronounced blend segregation during the tableting process. Furthermore, imaging was capable of quantitating the cimetidine bead content among the different blend ratios. Segregation testing (ASTM D6940-04 method) indicated that blends of coated cimetidine beads and placebo beads (50:50 ratio) also tended to segregate.

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Section: Introductionmentioning

confidence: 99%

NIR Spectroscopy Applications in the Development of a Compacted Multiparticulate System for Modified Release

et al. 2011

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“…Vice versa, absorbance bands constitute a complicating factor for the determination of physical properties of the solid. 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).…”

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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“…Then, in Equation (5), PCA scores are calculated using the loading vectors p pca_c calculated in Equation (2). The desired number of PCA components are removed in Equations 5±6.…”

Section: Correction Of New Samplesmentioning

confidence: 99%

An investigation of orthogonal signal correction algorithms and their characteristics

Svensson

Kourti

MacGregor

2002

Journal of Chemometrics

152

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Six different algorithms for orthogonal signal correction (OSC) are studied and compared both from an algorithmic point of view and from a prediction and analysis point of view. The algorithms have appeared under the names OSC (three alternative algorithms), direct orthogonalization (DO) and orthogonal projection to latent structures (OPLS). These algorithms can be divided into two groups. The first group has the ability to reduce the number of PLS components in the calibration models significantly by removing only one orthogonal component. The second group reduces the complexity of the calibration model by one PLS component for each orthogonal component removed. The methods are evaluated and compared using both simulated and real calibration data sets. In some cases the OSC algorithms can have quite different behaviors, such as when non-linearities are present. However, in all cases we have studied, none of the OSC algorithms provided a significant improvement in the calibration models over using PLS on the raw data. The main advantage with OSC may lie in the possibly easier interpretation and understanding from the analysis of corrected data. Analysis of the orthogonal information removed with OSC might also be beneficial.

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The application of multiple linear regression to the measurement of the median particle size of drugs and pharmaceutical excipients by near-infrared spectroscopy

Cited by 60 publications

References 19 publications

NIR Spectroscopy Applications in the Development of a Compacted Multiparticulate System for Modified Release

NIR Spectroscopy Applications in the Development of a Compacted Multiparticulate System for Modified Release

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

An investigation of orthogonal signal correction algorithms and their characteristics

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