Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy. Part I. System development and control.

An automated system for the on-line monitoring of powder blending processes is described. The system employs near-infrared (NIR) spectroscopy using fibre-optics and a graphical user interface (GUI) developed in the LabVIEW environment. The complete supervisory control and data analysis (SCADA) software controls blender and spectrophotometer operation and performs statistical spectral data analysis in real time. A data analysis routine using standard deviation is described to demonstrate an approach to the real-time determination of blend homogeneity.

On-line monitoring of powder blend homogeneity by near-infrared spectroscopy.

Near-infrared spectroscopy is evaluated as an on-line technique for monitoring the homogeneity of a pharmaceutical blend during the blending process. Blends containing 10% sodium benzoate (model active), which provided an aromatic functionality typical of many pharmaceutical compounds, 39% microcrystalline cellulose (Avicel PH102), 50% lactose, and 1% magnesium stearate were developed to mimic the properties of an actual pharmaceutical blend. A twin-shell V-blender was modified to allow installation of a diffuse reflectance fiber-optic probe at the axis of rotation, and spectra were collected during three experiments using a commercially available near-infrared spectrophotometer. In each experiment, blender control and spectral data collection were controlled by a compilation of software packages. The experiments detected spectral changes which eventually converged to a point of constant variance. Further analysis of the spectral data showed the blend is homogeneous long before a typical blending period is complete. Near-infrared spectroscopy has proven to be a feasible and effective method for the "real time" noninvasive determination of homogeneity in a pharmaceutical blend.

Appearance of discontinuities in spectra transformed by the piecewise direct instrument standardization procedure.

Several years ago, we noted that spectra transformed by the piecewise direct standardization (PDS) method may contain discontinuities. Having noticed that the problem was a recurring one, we studied it and recently diagnosed its source. Our investigations suggest that this problem also occurs in applications of window factor analysis, evolving factor analysis, and any other procedure that uses piecewise principal component models. In this work, we report the source of the problem and illustrate it with one example. A procedure is presented for eliminating the problem that is effective in PDS pattern recognition applications. Further work is needed to develop modified algorithms suitable for calibration applications.

A robotic dissolution system with on-line fiber-optic UV analysis.

An automated, robotic system has been developed with on-line UV fiber optics for real time dissolution analysis of solid dosage forms. The system is comprised of "off-the-shelf" hardware including a UV-Vis diode array spectrophotometer, fiber optic coupler, immersion probe, robot, and dissolution apparatus. The software system is modular with the functionalities of control, data acquisition, and spectral analysis separated into three Windows applications with communications performed via Dynamic Data Exchange (DDE). The fiber optic spectrophotometer collects a full spectrum over the range of 190-810 nm. Single wavelength UV analysis is performed on dosage forms in six dissolution vessels. The robotic system automates all facets of the analyses: measuring, degassing, and dispensing of the media; thermostating the media to physiologic temperature; dropping the dosage forms into the vessels; immersing the fiber optic probe at the appropriate time intervals; initiating the data acquisition, analyses, and reporting; and emptying and washing of the vessels prior to the next automated run. As a representative dosage form, 10 mg active tablets were selected and analyzed by this method. This fiber optic system has significantly improved the throughput of the robotic systems by eliminating the need for time consuming off-line HPLC or UV analyses. In addition, with the exception of system calibration, it is no longer necessary for laboratory personnel to come in contact with samples.

Observation of individual DNA molecules undergoing gel electrophoresis.

Individual DNA molecules undergoing agarose gel electrophoresis were viewed with the aid of a fluorescence microscope. Molecular shape and orientation were studied in both steady and pulsed electric fields. It was observed that (i) DNA macromolecules advanced lengthwise through the gel in an extended configuration, (ii) the molecules alternately contracted and lengthened as they moved, (iii) the molecules often became hooked around obstacles in a U-shape for extended periods, and (iv) the molecules displayed elasticity as they extended from both ends at once. A computer model has been developed that simulates the migration of the molecules in a rotating-field gel electrophoresis experiment.