Chemometrics in Process Analytical Technology (PAT)

Miller, Charles E.

doi:10.1002/9780470689592.ch12

Cited by 25 publications

(13 citation statements)

References 106 publications

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“…Out of space (OS, orthogonal distance from sample to PCA plane) and in space (IS, distance from PCA data mean (M) to projection of the sample) are useful statistics that assess general abnormality of a sample, relative to another set of samples. A useful outlier alarm must use both OS and IS, when Hotelling T2 and Qresiduals exceed the predefined limits [50]. The multiple spectra obtained may also be used to develop a criterion of blend uniformity.…”

Section: Obtaining Spectra and Selection Of Samples For The Calibratimentioning

confidence: 99%

A Procedure for Developing Quantitative Near Infrared (NIR) Methods for Pharmaceutical Products

Romañach

Román-Ospino

Alcalà

2016

Methods in Pharmacology and Toxicology

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The pharmaceutical industry uses procedures to describe all the instructions needed to perform a process in a consistent manner. Procedures are based on process knowledge and the desire to consistently meet desired specifications. This chapter proposes a procedure for the development of NIR partial least squares (PLS) calibration models for pharmaceutical applications. The chapter captures the lessons learned for more than a decade in studies where NIR spectroscopy has been used for quantitative determinations of drug concentration, moisture, polymorphs, and other important applications. Two examples of recent initiatives to develop NIR calibration models in a more efficient manner reducing the number of calibration samples are also discussed. The procedure differs from previously published guidelines since it is based on specific examples of method validations for pharmaceutical processes and provides clear instructions for method development and validation. The procedure and tutorial should advance the implementation of near infrared spectroscopic (NIRS) quantitative methods in the pharmaceutical industry.

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Section: Obtaining Spectra and Selection Of Samples For The Calibratimentioning

confidence: 99%

A Procedure for Developing Quantitative Near Infrared (NIR) Methods for Pharmaceutical Products

Romañach

Román-Ospino

Alcalà

2016

Methods in Pharmacology and Toxicology

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“…Spectral variable selection is performed in spectroscopic techniques, because otherwise the model would be affected by unwanted variability in the spectra instead of the analyte of interest [38]. Therefore, quantitative models based on Raman and NIR uses selected spectrum ranges [30][31][32][33], hence the same is performed for UV-Vis in this study.…”

Section: Spectral Variable Selectionmentioning

confidence: 99%

Development and Validation of an in-line API Quantification Method Using AQbD Principles Based on UV-Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process

et al. 2020

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A key principle of developing a new medicine is that quality should be built in, with a thorough understanding of the product and the manufacturing process supported by appropriate process controls. Quality by design principles that have been established for the development of drug products/substances can equally be applied to the development of analytical procedures. This paper presents the development and validation of a quantitative method to predict the concentration of piroxicam in Kollidon® VA 64 during hot melt extrusion using analytical quality by design principles. An analytical target profile was established for the piroxicam content and a novel in-line analytical procedure was developed using predictive models based on UV-Vis absorbance spectra collected during hot melt extrusion. Risks that impact the ability of the analytical procedure to measure piroxicam consistently were assessed using failure mode and effect analysis. The critical analytical attributes measured were colour (L* lightness, b* yellow to blue colour parameters—in-process critical quality attributes) that are linked to the ability to measure the API content and transmittance. The method validation was based on the accuracy profile strategy and ICH Q2(R1) validation criteria. The accuracy profile obtained with two validation sets showed that the 95% β-expectation tolerance limits for all piroxicam concentration levels analysed were within the combined trueness and precision acceptance limits set at ±5%. The method robustness was tested by evaluating the effects of screw speed (150–250 rpm) and feed rate (5–9 g/min) on piroxicam content around 15% w/w. In-line UV-Vis spectroscopy was shown to be a robust and practical PAT tool for monitoring the piroxicam content, a critical quality attribute in a pharmaceutical HME process.

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“…It is beyond the scope of this review to outline details of data preprocessing or multivariate spectroscopic analysis. A good introduction to these topics has already been written, for example, by Miller [60]…”

Section: Real‐time Analysis Of Small‐scale Drug Dissolution and Precimentioning

confidence: 99%

Analytical technologies for real-time drug dissolution and precipitation testing on a small scale

Kuentz

2015

Journal of Pharmacy and Pharmacology

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Objectives This review focuses on real-time analytics of drug dissolution and precipitation testing on a comparatively small scale. Key findings Miniaturisation of test equipment is an important trend in pharmaceutics, and several small-scale experiments have been reported for drug dissolution and precipitation testing. Such tests typically employ analytics in realtime. Fibre optic ultraviolet (UV) analytics has become a well-established method in this field. Novel imaging techniques are emerging that use visible or UV light; also promising is Fourier transform infrared imaging based on attenuated total reflection. More information than just a rate constant is obtained from these methods. The early phase of a dissolution process can be assessed and drug precipitation may eventually be observed. Some real-time techniques are particularly well suited to studying drug precipitation during formulation dispersion; for example, turbidity, focused beam reflectance measurement and Raman spectroscopy. Summary Small-scale dissolution tests equipped with real-time analytics have become important to screen drug candidates as well as to study prototype formulations in early development. Future approaches are likely to combine different analytical techniques including imaging. Miniaturisation started with mini-vessels or small vials and future assays of dissolution research will probably more often reach the level of parallel well plates and microfluidic channels.

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Chemometrics in Process Analytical Technology (PAT)

Cited by 25 publications

References 106 publications

A Procedure for Developing Quantitative Near Infrared (NIR) Methods for Pharmaceutical Products

A Procedure for Developing Quantitative Near Infrared (NIR) Methods for Pharmaceutical Products

Development and Validation of an in-line API Quantification Method Using AQbD Principles Based on UV-Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process

Analytical technologies for real-time drug dissolution and precipitation testing on a small scale

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