Process Development and Control with Recent New FBRM, PVM, and IR

Abstract

Process analytical technologies (PATs) have played an important role in process development and optimization throughout the pharmaceutical industry. Recent new PATs, including in-process video microscopy (PVM), a new generation of focused-beam reflectance measurement (FBRM), miniature process IR spectroscopy, and a flow IR sensor, have been evaluated, demonstrated, and utilized in the process development of many drug substances. First, PVM has filled a technical gap by providing the capability to study morphology for particle engineering by visualizing particles in real time without compromising the integrity of sample. Second, the new FBRM G series has closed gaps associated with the old S series with respect to probe fouling, bearing reliability, data analysis, and software integration. Third, a miniaturized process IR analyzer has brought forth the benefits of increased robustness, enhanced performance, improved usability, and ease of use, especially at scale-up. Finally, a miniaturized flow IR sensor has provided process flow chemistry development with a smaller, faster-performing, less expensive analytical tool.

Process analytical approaches for the coil-to-globule transition of poly(N-isopropylacrylamide) in a concentrated aqueous suspension

“…Such methods would also be applicable to the synthesis process itself [37]. In this study, the probe-based (fiber)optical technologies Photon Density Wave (PDW) spectroscopy [38–41], Focused Beam Reflectance Measurement (FBRM) [42–45], Particle Vision Microscope (PVM) measurement [46–48], and turbidity measurement [49–51] are applied to study the LCST of aqueous PNIPAM suspensions and additionally its heating and cooling rate dependency.…”

Effective sapphire repellency treatment to reduce fouling of a focused beam reflectance measurement (FBRM) probe in bituminous systems

“…[18] This method is not recommended as it increased fouling in the bitumen system, which is thought to be due to more hydrocarbon material coating the window. Hommema [18] suggested that other treatments that are optically transparent may be suitable as well, such as TEFLON 1 . Treatments are best removed with physical polishing using a fine polishing paste.…”

“…F ocused beam reflectance measurement (FBRM) is a measurement technique that allows for in-situ dynamic measurements of particle or drop sizes in a process. The FBRM probe is used extensively in crystallization processes and a number of processes with a solid dispersed phase, [1][2][3][4][5][6][7] as well as in the study of liquid/liquid dispersions [7][8][9][10][11][12] and more recently it has been applied to crude oil systems. [13][14][15][16][17][18] The FBRM probe directs a laser beam through a sapphire window into the fluid and collects backscattered light.…”

Application of PAT-Based Feedback Control Approaches in Pharmaceutical Crystallization

“…Nucleation and its mechanism are largely studied to get a further understanding of this key stage, mainly focusing on the qualitative and quantitative interactions between the solute, solvent, and external additives, and how the solute molecules self-assemble into different crystal forms, and what the exact mechanism and kinetics of nucleation is [3][4][5][6][7][8][9]. For growing crystals into the desired size and shape in the manufacturing process, a large portion of the literature is also reported to investigate the crystal growth process and its possible mechanisms [10][11][12][13][14][15]. Based on modeling and experimental techniques, many works are presently being performed on growth and shape control [10,12,[15][16][17][18].…”

“…FBRM can track the number of particles and chord length distribution in real-time, providing a quantitative calculation method for crystallization process modeling. The latest generation of FBRM overcomes the problem of probe contamination [11]. As a mature technology, Raman spectroscopy has been used to identify differences in polymorphisms, and it can perform qualitative and quantitative studies on solvent-mediated transformation, solution concentration, and the ratio of different crystal forms in solid mixtures [12].…”