Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

Context: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release.

Objective: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets.

Materials and methods: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet.

Results: IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol.

Discussion: IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets.

Conclusion: IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.     

Spectral characterization and ASTER-based lithological mapping of an ophiolite complex: A case study from Neyriz ophiolite, SW Iran

The Neyriz ophiolite occurs along the Zagros suture zone in SW Iran, and is part of a 3000-km obduction belt thrusting over the edge of the Arabian continent during the late Cretaceous. This complex typically consists of altered dunites and peridotites, layered and massive gabbros, sheeted dykes and pillow lavas, and a thick sequence of radiolarites. Reflectance and emittance spectra of Neyriz ophiolite rock samples were measured in the laboratory and their spectra were used as endmembers in a spectral feature fitting (SFF) algorithm. Laboratory spectral reflectance measurements of field samples showed that in the visible through shortwave infrared (VNIR-SWIR) wavelength region the ultramafic and gabbroic rocks are characterized by ferrous-iron and Fe, MgOH spectral features, and the pillow lavas and radiolarites are characterized by spectral features of ferric-iron and AlOH. The laboratory spectral emittance spectra also revealed a wide wavelength range of SiO spectral features for the ophiolite rock units. After continuum removal of the spectra, the SFF classification method was applied to the VNIR + SWIR 9-band stack, and to the 11-band data set of SWIR and TIR data sets of the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor, using field spectra as training sets for evaluating the potential of these data sets in discriminating ophiolite rock units. Output results were compared with the geological map of the area and field observations, and were assessed by the use of confusion matrices. The assessment showed, in terms of kappa coefficient, that the SFF classification method with continuum removal applied to the SWIR data achieved excellent results, which were distinctively better than those obtained using VNIR + SWIR data and TIR data alone.     

The Chromatin Architectural Protein CTCF Is Critical for Cell Survival upon Irradiation-Induced DNA Damage

CTCF is a nuclear protein initially discovered for its role in enhancer-promoter insulation. It has been shown to play a role in genome architecture and in fact, its DNA binding sites are enriched at the borders of chromatin domains. Recently, we showed that depletion of CTCF impairs the DNA damage response to ionizing radiation. To investigate the relationship between chromatin domains and DNA damage repair, we present here clonogenic survival assays in different cell lines upon CTCF knockdown and ionizing irradiation. The application of a wide range of ionizing irradiation doses (0–10 Gy) allowed us to investigate the survival response through a biophysical model that accounts for the double-strand breaks’ probability distribution onto chromatin domains. We demonstrate that the radiosensitivity of different cell lines is increased upon lowering the amount of the architectural protein. Our model shows that the deficiency in the DNA repair ability is related to the changes in the size of chromatin domains that occur when different amounts of CTCF are present in the nucleus.     

Delamination detection with carbon nanotube thread in self-sensing composite materials

Laminated composite materials can reach high mechanical properties at low weight. Composite materials, however, are susceptible to damage due to their low interlaminar mechanical properties and poor heat and charge transport in the transverse direction to the laminate. Moreover, methods to inspect and ensure the reliability of composites are expensive and labor intensive. Recently carbon nanotube forests were spun into thread that is tough and electrically conductive. The thread was integrated into composite materials and used for the first time as a sensor to monitor strains and detect damage including delamination in the material. These self-sensing composites were found to be very sensitive to damage and will help to revolutionize the maintenance of composite structures, which will now be based on their condition and not their amount of use.     

Mapping the total phosphorus concentration of biosolid amended surface soils using LANDSAT TM data

Conventional methods for soil sampling and analysis for soil variability in chemical characteristics are too time-consuming and expensive for multi-seasonal monitoring over large-scale areas. Hence, the objectives of this study are: 1) to determine changes in chemical concentrations of soils that are amended with treated sewage sludge; and 2) to determine if LANDSAT TM data can be used to map surface chemical characteristics of such amended soils. For this study, we selected two fields in NW Ohio, designated as F34 and F11, that had been applied with 34 and 11 ton acre^− 1 of biosolids, respectively. Soil samples from a total of 70 sampling locations across the two fields were collected one day prior to LANDSAT 5 overpass and were analyzed for several elemental concentrations. The accumulation of Ba, Cd, Cu, S and P were found to be significantly higher in the surface soils of field F34, compared to field F11. Regression equations were established to search for algorithms that could map these five elemental concentrations in the surface soils using six, dark-object-subtracted (DOS) LANDSAT TM bands and the 15 non-reciprocal spectral ratios derived from these six bands for the May 20, 2005, LANDSAT 5 TM image. Phosphorus (P) had the highest R² adjusted value (67.9%) among all five elements considered, and the resulting algorithm employed only spectral ratios. This model was successfully tested for robustness by applying it to another LANDSAT TM image obtained on June 5, 2005. Our results enabled us to conclude that LANDSAT TM imagery of bare-soil fields can be used to quantify and map the spatial variation of total phosphorous concentration in surface soils. This research has significant implications for identification and mapping of areas with high P, which is important for implementing and monitoring the best phosphorous management practices across the region.     

Screening of Soil Amendments for Efficient Water-Holding Capacity Based on a Rainfall-Infiltration Model in a Vertisol

A simulation study was conducted with five soil amendments, viz., goat manure, coir pith, phosphogypsum, polyacrylamide, and a control at two rainfall intensities of 60 and 120?mm?h?1 under dry and wet soil conditions in a clay loam vertisol with the objective of identifying a superior soil amendment for maximum infiltration and suitable soil aggregate stability. The F-test based on analysis of variance of infiltration data indicated that soil amendments, rainfall intensities, and soil conditions were significantly different from each other. Based on least significant difference test, polyacrylamide was found to be superior with a significantly higher infiltration, compared to all other amendments. An exponential model of infiltration over a time interval was calibrated for each soil amendment under dry and wet soil conditions. Based on the model, polyacrylamide and phosphogypsum were found to have a better soil aggregate stability compared to other soil amendments. The exponential model gave a significant predictability of instantaneous infiltration ranging from 0.75 to 0.99 under different situations. A grouping of treatments based on mean and coefficient of variation of infiltration in comparison with soil aggregate stability values indicated that polyacrylamide was superior under different situations in the study. Phosphogypsum was found to be the second best soil amendment with a relatively lower infiltration compared to polyacrylamide, but with a better soil aggregate stability compared to other soil amendments. Coir pith, goat manure, and control gave a significantly lower infiltration with a relatively higher variation compared to polyacrylamide and phosphogypsum, and also had a relatively lower soil aggregate stability under different situations examined in the study.     

Predictability of process resource usage: a measurement-based studyon UNIX

A statistical approach is developed for predicting the CPU time, the file I/O, and the memory requirements of a program at the beginning of its life, given the identity of the program. Initially, statistical clustering is used to identify high-density regions of process resource usage. The identified regions form the states for building a state-transition model to characterize the resource usage of each program in its past executions. The prediction scheme uses the knowledge of the program's resource usage in its last execution together with its state-transition model to predict the resource usage in its next execution. The prediction scheme is shown to work using process resource-usage data collected from a VAX 11/780 running 4.3 BSD Unix. The results show that the predicted values correlate strongly with the actual; the coefficient of correlation between the predicted and actual values for CPU time is 0.84. The errors in prediction are mostly small and are heavily skewed toward small values     

Safety, pharmacokinetics and biodistribution studies of a beta-galactoside prodrug of doxorubicin for improvement of tumor selective chemotherapy

Anthracycline antibiotics, particularly doxorubicin (DOX) and daunorubicin, have been used extensively in the treatment of human malignancies. However, cardiotoxicity and multidrug resistance are significant problems that limit the clinical efficacy of such agents. Rational design to avoid these side effects includes strategies such as drug targeting and prodrug synthesis. The DOX prodrug N-(beta-D-glucopyranosylbenzyloxycarbonyl)-doxorubicin (prodrug 1) was synthesized for specific activation by beta-galactosidase, which is expected to release in necrotic areas of tumor lesions. Described here is the safety, pharmacokinetics, and biodistribution studies of a beta-galactoside prodrug of DOX. In vivo safety evaluation was done in the Ehrlich Ascites Carcinoma (EAC) tumor model. The dose of DOX was 8 mg/kg and the dose of prodrug was 8 mg/kg and 24 mg/kg of DOX equivalents. Our results on cytotoxicity, which demonstrated compression in the number of EAC cells and their viability, substantiate these data. Prodrug 1 was safe up to a dose of 24 mg/kg of DOX equivalents in EAC mice. The pharmacokinetics and biodistribution of prodrug (300 mg/kg) in normal mice were determined and compared with DOX (20 mg/kg). Administration of DOX in normal mice resulted in a peak plasma concentration of 19.45 microM (t = 30 minutes). Prodrug injection resulted in 3- to 16-fold lower concentrations in the tissues of normal mice. As it is more polar, lower levels were observed in tissues and plasma in contrast to the parent compound DOX. In vivo safety studies have shown that prodrug 1 had a maximum tolerated dose compared with DOX and led to improved pharmacokinetics in normal mice.