Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer.

Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulation's resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing.

Real-time assessment of granule densification in high shear wet granulation and application to scale-up of a placebo and a brivanib alaninate formulation.

Real-time monitoring and control of high shear wet granulation (HSWG) using process analytical technologies is crucial to process design, scale-up, and reproducible manufacture. Although significant progress has been made in real-time measurement of granule size distribution using focused beam reflectance measurement (FBRM), real-time in-line assessment of granule densification remains challenging. In this study, a drag force flow (DFF) sensor was developed and used to probe wet mass consistency in real-time. In addition, responses from FBRM and DFF sensors were compared to assess complementarity of information on granulation progress from the two probes. A placebo and a brivanib alaninate formulation were granulated with different concentrations of binder or water, respectively, while measuring granule size growth, densification, and DFF sensor response. The DFF sensor was able to quantitatively characterize with high resolution a response of wet mass consistency distinct from granule size distribution. The wet mass consistency parameter correlated well with granule densification, which was shown as a critical material attribute that correlated with tablet dissolution. In addition, application of DFF sensor to scale-up of granulation was demonstrated. These results showed the value of wet mass consistency measurement using DFF for WG monitoring and control.

Use of Penning ionization electron spectroscopy in plasma for measurements of environmental gas constituents.

A breadboard GC detector based on Penning ionization electron spectroscopy in plasma (PIES) was investigated. The PIES detector was set up in series with a gas chromatograph and a thermal conductivity detector. Two-dimensional PIES chromatograms were recorded for carbon monoxide, carbon dioxide, and methane. The analytes were identified independently of the GC retention time, and their concentrations were measured in a range between 1 and 100 ppm. PIES spectra for methane were observed for the first time and displayed two characteristic peaks with electron energies of 7.1 and 5.4 eV. Rate coefficients for Penning ionization due to collisions between 2(3)S helium metastable atoms and analyte molecules under study were found to be k*(CO) = (0.7 +/- 0.2) x 10(-10), k*(CO2) = (1.8 +/- 0.7) x 10(-10), k*(7.1 CH4) = (4.7 +/- 0.6) x 10(-10), and k*(5.4 CH4) = (8 +/- 2) x 10(-10) cm(3)/s. The work provides the basis for the development of a portable and robust analytical platform capable of in situ real-time monitoring of greenhouse gases, with a perspective toward laboratory-on-chip realization.

Micro-optical force sensor concept based on whispering gallery mode resonators.

A micro-optical force sensor concept based on the morphology-dependent shifts of optical modes of dielectric microspheres is investigated. The optical resonances, commonly referred to as the whispering gallery modes (WGM), were excited by evanescently coupling light from a tunable diode laser using a tapered single-mode fiber. A compressive force applied to the sphere induces a change in both the shape and the index of refraction of the sphere leading to a shift in WGM. By tracking the shifts, the force magnitude is determined using solid silica as well as solid and hollow Polymethyl-methacrylate (PMMA) microsphere resonators. A measurement sensitivity as high as dlambda/dF=7.664 nm/N was demonstrated with a 960 mum hollow PMMA sphere.

Ionization processes in fluorescent lamps: evaluation of the Hg chemi-ionization rate coefficients.

Chemi-ionization by two mercury atoms to produce mercury atomic and molecular ions has been considered an important process in fluorescent lamps (FLs) for a quarter of a century. Despite the absence of reliable data, these processes have been included in a number of numerical models to help explain some of the experimental observations. These models have shown that the most important process is the Penning ionization of two Hg metastable atoms Hg(6(3)P2)+Hg(6(3)P2) --> Hg(+)+Hg(6(1)S0)+e. Although there is no experimental measurement of this cross section, modelers have typically used values implied from measurements of other chemi-ionization cross sections, or values obtained by fitting parameters to numerical models to obtain agreement with experiment. Recent theoretical investigations have indicated that the cross sections for the important processes may not be as large as previously thought. The aim of the present paper is to critically review the historical development of studies of chemi-ionization in fluorescent lamps and to present new experimental evidence which is consistent with the theoretical calculations and contradicts the conclusions from previously published experiments.