Maury White - Academia.edu (original) (raw)

Papers by Maury White

Research paper thumbnail of Quality-by-Design (QbD): An integrated multivariate approach for the component quantification in powder blends

International Journal of Pharmaceutics, May 8, 2009

The objective of this study was to develop an integrated multivariate approach to quantify the co... more The objective of this study was to develop an integrated multivariate approach to quantify the constituent concentrations of both drug and excipients of powder blends. A mixture design was created to include 26 powder formulations consisting of ibuprofen as the model drug and three excipients (HPMC, MCC, and Eudragit L100-55). The mixer was stopped at various time points to enable nearinfrared (NIR) scan of the powder mixture and sampling for UV assay. Partial least square (PLS), principal component regression (PCR), and multiple linear regression (MLR) models were established to link the formulation concentrations with the Savitzky-Golay 1st derivative NIR spectral data at various characteristic wavelengths of each component. PLS models based on the NIR data and UV data were calibrated and validated. They predicted the main components' concentrations well in the powder blends, although prediction errors were larger for minor components. As expected from the completerandom-mixture (CRM) model, the measurement uncertainties were higher for minor components in the powder formulations. The prediction performance differences between the NIR model and UV model were explained in the context of scale of scrutiny and model applicability. The importance of understanding excipient variability in powder blending and its implication for blending homogeneity assessment is highlighted.

Research paper thumbnail of Quality-by-Design (QbD): Examining the Impact of Process Variables On Particle Size Distribution for a Pharmaceutical Co-Precipitation Process Using Real-Time Lasentec FBRM and PVM Process Monitoring and Design of Experiments (DoE) Approach

Particle size distribution (PSD) is a critical quality attribute for many pharmaceutical unit ope... more Particle size distribution (PSD) is a critical quality attribute for many pharmaceutical unit operations, such as crystallization, granulation, mixing, and tabletting. Various formulation and process factors could impact PSD to different extents of a particular unit operation. Therefore, it is important to know how those variables impact the PSD and how to optimize various variables to achieve a desired PSD. These two aspects constitute an essential element of pharmaceutical process Quality-by-Design (QbD). In this work, a pharmaceutical (naproxen) and a polymer (eudragit) co-precipitation process was monitored in real-time by using Lasentec FBRM and PVM technologies. The impact of various process variables such as co-precipitation slurry temperature, non solvent addition rate, and stirring rate on the PSD of the co-precipiate were examined systematically, using a design of experiments (DoE) approach. The results were interpreted and discussed in the context of particulate process e...

Research paper thumbnail of Integrated Process Analytical Technology Approach for Nucleation Induction Time Measurement and Nucleation Mechanism Assessment for a Dynamic Multicomponent Pharmaceutical Antisolvent Crystallization System

Industrial & Engineering Chemistry Research

A comprehensive, real-time PAT process monitoring scheme of using near-infrared (NIR) spectroscop... more A comprehensive, real-time PAT process monitoring scheme of using near-infrared (NIR) spectroscopy, focused beam reflectance measurement (FBRM), and particle vision microscopy (PVM) was established for process characterization and process understanding of a model dynamic multicomponent pharmaceutical antisolvent crystallization system. The NIR spectra were subjected to principal component analysis (PCA) to construct the process trajectory; and the final products were characterized by X-ray powder diffraction (XRPD), raman spectrometry, and microscopy. Regardless of the PAT technique (i.e., the NIR–PCA method, the FBRM method, and the PVM method) used, this study shows that the nucleation induction time (tind) increases with temperature. In addition, correlations were observed with R2 of 0.70–0.98 between PVM method and FBRM method and of 0.58–0.84 between NIR–PCA method and FBRM method. Accounting for the dynamic nature of the experiments and changes in the liquid volume (V) as a fu...

Research paper thumbnail of Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for real-time monitoring and mapping the state of a pharmaceutical coprecipitation process

In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen)... more In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen) and a polymer (eudragit) coprecipitation process: real-time in-line near-infrared (NIR) absorbance monitoring, real-time on-line turbidity monitoring, and in situ crystal size monitoring. The data and information obtained through these three monitoring techniques confirmed the observation of the onsets of three distinct stages: incubation, nucleation, and crystal growth. The process trajectory constructed based on results of applying principal component analysis (PCA) to either process NIR spectra data or process turbidity profile, clearly demonstrated that various distinguishable process events, including incubation, nucleation, and crystal growth, could be accurately tracked and differentiated. These findings were further supported by process knowledge and information, such as process design, process sequence, thermodynamic and mass-transfer analysis. Therefore, this work provides a case study that illustrated a rational approach to develop a science-based and knowledge-based process monitoring strategy, which is essential for establishing both a suitable process control strategy and an operational process space for a pharmaceutical unit operation.

Research paper thumbnail of Real time monitoring of bioreactor mAb IgG3 cell culture process dynamics via Fourier transform infrared spectroscopy: Implications for enabling cell culture process analytical technology

AbstractCompared to small molecule process analytical technology (PAT) applications, biotechnolog... more AbstractCompared to small molecule process analytical technology (PAT) applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufacturing biotechnology drug products. However, the use of inline Fourier transform infrared (FTIR) spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites (including glucose, glutamine, ...

Research paper thumbnail of Quality-by-Design (QbD): An integrated multivariate approach for the component quantification in powder blends

International Journal of Pharmaceutics, May 8, 2009

The objective of this study was to develop an integrated multivariate approach to quantify the co... more The objective of this study was to develop an integrated multivariate approach to quantify the constituent concentrations of both drug and excipients of powder blends. A mixture design was created to include 26 powder formulations consisting of ibuprofen as the model drug and three excipients (HPMC, MCC, and Eudragit L100-55). The mixer was stopped at various time points to enable nearinfrared (NIR) scan of the powder mixture and sampling for UV assay. Partial least square (PLS), principal component regression (PCR), and multiple linear regression (MLR) models were established to link the formulation concentrations with the Savitzky-Golay 1st derivative NIR spectral data at various characteristic wavelengths of each component. PLS models based on the NIR data and UV data were calibrated and validated. They predicted the main components' concentrations well in the powder blends, although prediction errors were larger for minor components. As expected from the completerandom-mixture (CRM) model, the measurement uncertainties were higher for minor components in the powder formulations. The prediction performance differences between the NIR model and UV model were explained in the context of scale of scrutiny and model applicability. The importance of understanding excipient variability in powder blending and its implication for blending homogeneity assessment is highlighted.

Research paper thumbnail of Quality-by-Design (QbD): Examining the Impact of Process Variables On Particle Size Distribution for a Pharmaceutical Co-Precipitation Process Using Real-Time Lasentec FBRM and PVM Process Monitoring and Design of Experiments (DoE) Approach

Particle size distribution (PSD) is a critical quality attribute for many pharmaceutical unit ope... more Particle size distribution (PSD) is a critical quality attribute for many pharmaceutical unit operations, such as crystallization, granulation, mixing, and tabletting. Various formulation and process factors could impact PSD to different extents of a particular unit operation. Therefore, it is important to know how those variables impact the PSD and how to optimize various variables to achieve a desired PSD. These two aspects constitute an essential element of pharmaceutical process Quality-by-Design (QbD). In this work, a pharmaceutical (naproxen) and a polymer (eudragit) co-precipitation process was monitored in real-time by using Lasentec FBRM and PVM technologies. The impact of various process variables such as co-precipitation slurry temperature, non solvent addition rate, and stirring rate on the PSD of the co-precipiate were examined systematically, using a design of experiments (DoE) approach. The results were interpreted and discussed in the context of particulate process e...

Research paper thumbnail of Integrated Process Analytical Technology Approach for Nucleation Induction Time Measurement and Nucleation Mechanism Assessment for a Dynamic Multicomponent Pharmaceutical Antisolvent Crystallization System

Industrial & Engineering Chemistry Research

A comprehensive, real-time PAT process monitoring scheme of using near-infrared (NIR) spectroscop... more A comprehensive, real-time PAT process monitoring scheme of using near-infrared (NIR) spectroscopy, focused beam reflectance measurement (FBRM), and particle vision microscopy (PVM) was established for process characterization and process understanding of a model dynamic multicomponent pharmaceutical antisolvent crystallization system. The NIR spectra were subjected to principal component analysis (PCA) to construct the process trajectory; and the final products were characterized by X-ray powder diffraction (XRPD), raman spectrometry, and microscopy. Regardless of the PAT technique (i.e., the NIR–PCA method, the FBRM method, and the PVM method) used, this study shows that the nucleation induction time (tind) increases with temperature. In addition, correlations were observed with R2 of 0.70–0.98 between PVM method and FBRM method and of 0.58–0.84 between NIR–PCA method and FBRM method. Accounting for the dynamic nature of the experiments and changes in the liquid volume (V) as a fu...

Research paper thumbnail of Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for real-time monitoring and mapping the state of a pharmaceutical coprecipitation process

In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen)... more In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen) and a polymer (eudragit) coprecipitation process: real-time in-line near-infrared (NIR) absorbance monitoring, real-time on-line turbidity monitoring, and in situ crystal size monitoring. The data and information obtained through these three monitoring techniques confirmed the observation of the onsets of three distinct stages: incubation, nucleation, and crystal growth. The process trajectory constructed based on results of applying principal component analysis (PCA) to either process NIR spectra data or process turbidity profile, clearly demonstrated that various distinguishable process events, including incubation, nucleation, and crystal growth, could be accurately tracked and differentiated. These findings were further supported by process knowledge and information, such as process design, process sequence, thermodynamic and mass-transfer analysis. Therefore, this work provides a case study that illustrated a rational approach to develop a science-based and knowledge-based process monitoring strategy, which is essential for establishing both a suitable process control strategy and an operational process space for a pharmaceutical unit operation.

Research paper thumbnail of Real time monitoring of bioreactor mAb IgG3 cell culture process dynamics via Fourier transform infrared spectroscopy: Implications for enabling cell culture process analytical technology

AbstractCompared to small molecule process analytical technology (PAT) applications, biotechnolog... more AbstractCompared to small molecule process analytical technology (PAT) applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufacturing biotechnology drug products. However, the use of inline Fourier transform infrared (FTIR) spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites (including glucose, glutamine, ...