Examination of Components of Variance for A Production Scale, Low Dose Powder Blend and Resulting Tablets

A study was performed to quantify the contributions of the different components comprising the total variance term observed following the analysis of content uniformity testing of powder blends and tablets. A full scale (400 kg) blend study was performed on a low dose tablet formulation (drug content = 0.13%). Content uniformity samples were pulled from throughout the blender using a pocket type probe thief in a manner which allowed the blend to be assessed for both homogeneity and sample to sample variability at a given location. Tablets were compressed from the batch and assayed for content uniformity. Sampling error accounted for approximately 75% of the variance observed following analysis of drug content in the powder blends. The estimated total variance for the powder blend was approximately twice that observed for tablets compressed from the mixture. The analytical contribution to the total variance term was minor. The difference between the estimated total variance terms for powder blend and tablets was attributed to the superior sampling efficiency of the tablet press versus the sample thief. The results of the study support the use of wider specifications for powder blends than the tablets compressed from the mixture.     

Ignition Mechanisms in Monopropellants

The sensitivity of liquid monopropellants is examined when subjected to compression ignition, including the case of purposeful sensitization with air bubbles; and frictional heating. The monopropellant is a hydroxylammonium nitrate (HAN)-based propellant. Conditions are identified which will likely result in ignition from rapid compression. Ignition from frictional heating associated with hydroynamic flow is less certain, however attempts to model this phenomenon theoretically have been made.     

A WISE method for designing IIR filters

The problem of designing optimal digital IIR filters with frequency responses approximating arbitrarily chosen complex functions is considered. The real-valued coefficients of the filter's transfer function are obtained by numerical minimization of carefully formulated cost, which is referred here to as the weighted integral of the squared error (WISE) criterion. The WISE criterion linearly combines the WLS criterion that is used in the weighted least squares approach toward filter design and some time-domain components. The WLS part of WISE enforces the quality of the frequency response of the designed filter, while the time-domain part of the WISE criterion restricts the positions of the filter's poles to the interior of an origin-centred circle with arbitrary radius. This allows one not only to achieve stability of the filter but also to maintain some safety margins. A great advantage of the proposed approach is that it does not impose any constraints on the optimization problem and the optimal filter can be sought using off-the-shelf optimization procedures. The power of the proposed approach is illustrated with filter design examples that compare favorably with results published in research literature     

Two-minute miniprep method for plasmid DNA isolation

An extremely rapid method, INSTA-PREP, has been developed to prepare plasmid DNA from 1 to 3 mL miniprep Escherichia coli bacterial cultures. Direct extraction of plasmid DNA from E. coli bacterial cells is achieved by a two-phase solution consisting of phenol-chloroform-isoamyl alcohol and water or buffer with efficient separation of the phases by centrifugation in the presence of the INSTA-PREP gel barrier material. Processing time, from E. coli culture to usable plasmid DNA, is two minutes or less per sample. Supercoiled plasmid DNA yields ranged from 3 to 10 micrograms per mL of culture depending on plasmid copy number. Plasmid DNAs prepared by INSTA-PREP were analyzed and are suitable for use in molecular biology procedures including restriction digestion, ligation with T4 DNA ligase, bacterial transformation, PCR, cultured cell transfection and T7 DNA polymerase or thermostable DNA polymerase-mediated dideoxynucleotide sequencing.     

Spectral analysis of randomly sampled signals: suppression of aliasing and sampler jitter

Nonuniform sampling can facilitate digital alias-free signal processing (DASP), i.e., digital signal processing that is not affected by aliasing. This paper presents two DASP approaches for spectrum estimation of continuous-time signals. The proposed algorithms, named the weighted sample (WS) and weighted probability (WP) density functions, respectively, utilize random sampling to suppress aliasing. Both methods produce unbiased estimators of the signal spectrum. To achieve this effect, the computational procedure for each method has been suitably matched with the probability density function characterising the pseudorandom generators of the sampling instants. Both proposed methods are analyzed, and the qualities of the estimators they produce have been compared with each other. Although none of the proposed spectrum estimators is universally better than the other one, it has been shown that in practical cases, the WP estimator produces generally smaller errors than those obtained from WS estimation. A practical limitation of the approaches caused by the sampling-instant jitter is also studied. It has been proven that in the presence of jitter, the theoretically infinite bandwidths of WS and WP signal analyses are limited. The maximum frequency up to which these analyses can be performed is inversely proportional to the size of the jitter.     

Calibration-free estimates of batch process yields and detection of process upsets using in situ spectroscopic measurements and nonisothermal kinetic models: 4-(dimethylamino)pyridine- catalyzed esterification of butanol

In this paper, we report the use of an NIR fiber-optic spectrometer with a high-speed diode array for calibration-free monitoring and modeling of the reaction of acetic anhydride with butanol using the catalyst 4-(dimethylamino)pyridine in a microscale batch reactor. Acquisition of spectra at 5 ms/scan gave information relevant for modeling these fast batch processes with a single multibatch kinetic model. Nonlinear fitting of a first-principles model directly to the reaction spectra gave calibration-free estimates of time-dependent concentration profiles and pure component spectra. The amount of catalyst was varied between different batches to permit accurate estimation of its effect in the multiway model. A wide range of different models with increasing complexity could be fit to each batch individually with low residuals and apparent low lack of fit. However, only one model properly estimated the concentration profiles when all five batches were fitted simultaneously in a multiway kinetic model. Inclusion of on-line temperature measurements and use of an Arrhenius model for the estimated rate constant gave significantly improved model fits compared to an isothermal kinetic model. Augmentation of prerun batches with data from an additional batch permitted model-based forecasts of reaction trajectories, reaction yield, reaction end points, and process upsets. One batch with added water to simulate a process upset was easily detected by the calibration free process model.