Quality control of pharmaceuticals with NIR: From lab to process line

This work describes a general framework for assessing the active pharmaceutical ingredient (API) and excipient concentrations simultaneously in pharmaceutical dosage forms based on laboratory-scale measurements. The work explores the comprehensive development of a near infrared (NIR) analytical protocol for the quantification of the API and excipients of a pharmaceutical formulation. The samples were based on a paracetamol (API) formulation with three excipients: microcrystalline cellulose, talc, and magnesium stearate. The developed method was based on laboratory-scale samples as calibration samples and pilot-scale samples (powders and tablets) as model test samples. Both types of samples were produced according to an experimental design. The samples were measured in reflectance mode in a Fourier-transform NIR spectrometer. Additionally, a new method for determining the minimum number of calibration samples was proposed. It was concluded that the use of laboratory-scale samples to construct the calibration set is an effective way to ensure the concentration variability in the development of calibration models for industrial applications. With this method, both API and excipients can be determined in high-throughput applications in the pharmaceutical industry.     

β‐Hydrogen transfer from poly(methyl methacrylate) propagating radicals to the nitroxide SG1: Analysis of the chain‐end and determination of the rate constant

Methyl methacrylate (MMA) was polymerized in bulk at 70 °C in the presence of an alkoxyamine initiator with low dissociation temperature (the so‐called BlocBuilder?) and increasing amounts of free N‐tert‐butyl‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl) nitroxide (SG1). Low final monomer conversions were reached, indicating a loss in radical activity due to side reactions such as irreversible homoterminations between the propagating radicals and β‐hydrogen transfer (also called disproportionation) from a propagating radical to a free‐SG1 nitroxide. Proton NMR and MALDI‐TOF mass spectrometry were used to analyze the polymer chain‐ends and to clearly identify the main mechanism of irreversible termination. In particular, it was shown that all polymer chains were terminated by an alkene function in the presence of a large excess of free SG1, meaning that β‐hydrogen transfer from PMMA propagating radicals to the nitroxide SG1 was the major chain‐stopping event. On the other hand, for a low excess of free SG1, the two termination modes coexisted. Kinetic modeling was then performed using the PREDICI software, and the rate constant of β‐hydrogen transfer, k_βHtr, was estimated to be 1.69 × 10³ L mol^?1 s^?1 at 70 °C. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6333–6345, 2008     

Ternary blends of phenoxy/SAN/poly(-ε-caprolactone)

The compatibilizing effect of poly(ε-caprolactone) (PCL) on the blends of two immiscible polymers, poly(hydroxy ether of bisphenol A) (phenoxy) and poly(styrene-co-acrylonitrile) (SAN) has been investigated. The phase behavior of the ternary blends was affected by the AN content in the SAN copolymers and a maximum miscible region was observed at 19.5 wt % of AN. The effect of AN content on the phase behavior of the ternary blends was interpreted in terms of the relative magnitude of the segmental interaction energy densities, which were obtained by combining a melting point depression and an extended binary interaction model. When a small amount of PCL was added to the phenoxy/SAN blends, the phase morphology showed a finer phase dispersion, indicating that the interfacial tension between the phenoxy and SAN is considerably reduced. However, the improvement in tensile properties was limited despite the morphological change with the PCL content. From the results of the DSC measurements, SEM, and tensile testing, it was understood that the PCL acted as a compatibilizer for the immiscible phenoxy/SAN blends. © 1994 John Wiley & Sons, Inc.     

A New Heuristic Method for the Permutation Flow Shop Scheduling Problem

A new heuristic method for the permutation flow shop scheduling problem is presented and compared with two other heuristics named NEH and SPIRIT. The new heuristic method is based on a property of the scheduling problem that provides an upper bound on the idle time of the last machine between any two adjacent jobs regardless of their position in the sequence of jobs. The results from computational experience have shown that the new heuristic outperforms, in solution quality, all others for problems having up to 50 jobs and 30 machines.     

Dynamic updates of the barrier parameter in primal-dual methods for nonlinear programming

We introduce a framework in which updating rules for the barrier parameter in primal-dual interior-point methods become dynamic. The original primal-dual system is augmented to incorporate explicitly an updating function. A Newton step for the augmented system gives a primal-dual Newton step and also a step in the barrier parameter. Based on local information and a line search, the decrease of the barrier parameter is automatically adjusted. We analyze local convergence properties, report numerical experiments on a standard collection of nonlinear problems and compare our results to a state-of-the-art interior-point implementation. In many instances, the adaptive algorithm reduces the number of iterations and of function evaluations. Its design guarantees a better fit between the magnitudes of the primal-dual residual and of the barrier parameter along the iterations.     

Development of a microfluidic device for simultaneous mixing and pumping

We conducted experimental and numerical studies aimed at developing a microfluidic device capable of simultaneous mixing while pumping. The proposed multifunctional device makes use of alternating current electroosmotic flow and adopts an array of planar asymmetric microelectrodes with a diagonal or herringbone shape. The pumping performance was assessed in terms of the fluid velocity at the center of the microchannel, obtained by micro PIV. To assess the mixing, flow visualizations were carried out over the electrodes to verify the lateral flows. The mixing degree was quantified in terms of a mixing efficiency obtained by three-dimensional numerical simulations. The results showed that simultaneous mixing and pumping was achieved in the channels with diagonal or herringbone electrode configurations. A herringbone electrode configuration showed better pumping compared with a reference, as well as enhanced mixing.