Loading of itraconazole into porous silica and silicon microparticles: characterization and dissolution tests

Most new drug molecules discovered today suffer from poor bioavailability. Poor oral bioavailability results mainly from poor dissolution properties of hydrophobic drug molecules, because the drug dissolution is often the rate-limiting event of the drug’s absorption through the intestinal wall into the systemic circulation. During the last few years, the use of mesoporous silica and silicon particles as oral drug delivery vehicles has been widely studied, and there have been promising results of their suitability to enhance the physicochemical properties of poorly soluble drug molecules. Mesoporous silica and silicon particles can be used to enhance the solubility and dissolution rate of a drug by incorporating the drug inside the pores, which are only a few times larger than the drug molecules, and thus, breaking the crystalline structure into a disordered, amorphous form with better dissolution properties. Also, the high surface area of the mesoporous particles improves the dissolution rate of the incorporated drug. In addition, the mesoporous materials can also enhance the permeability of large, hydrophilic drug substances across biological barriers. T he loading process of drugs into silica and silicon mesopores is mainly based on the adsorption of drug molecules from a loading solution into the silica or silicon pore walls. There are several factors that affect the loading process: the surface area, the pore size, the total pore volume, the pore geometry and surface chemistry of the mesoporous material, as well as the chemical nature of the drugs and the solvents. Furthermore, both the pore and the surface structure of the particles also affect the drug release kinetics. In this study, the loading of itraconazole into mesoporous silica (Syloid AL-1 and Syloid 244) and silicon (TOPSi and TCPSi) microparticles was studied, as well as the release of itraconazole from the microparticles and its stability after loading. Itraconazole was selected for this study because of its highly hydrophobic and poorly soluble nature. Different mesoporous materials with different surface structures, pore volumes and surface areas were selected in order to evaluate the structural effect of the particles on the loading degree and dissolution behaviour of the drug using different loading parameters. The loaded particles were characterized with various analytical methods, and the drug release from the particles was assessed by in vitro dissolution tests. The results showed that the loaded drug was apparently in amorphous form after loading, and that the loading process did not alter the chemical structure of the silica or silicon surface. Both the mesoporous silica and silicon microparticles enhanced the solubility and dissolution rate of itraconazole. Moreover, the physicochemical properties of the particles and the loading procedure were shown to have an effect on the drug loading efficiency and drug release kinetics. Finally, the mesoporous silicon particles loaded with itraconazole were found to be unstable under stressed conditions (at 38 qC and 70 % relative humidity).

Effect of relative density and confining pressure on Poisson ratio from bender and extender elements tests

By using the bender and extender elements tests, together with measurements of the travel times of shear (S) and primary (P) waves, the variation of Poisson ratio (nu) was determined for dry sands with respect to changes in relative densities and effective confining pressures (sigma(3)). The tests were performed for three different ranges of particle sizes. The magnitude of the Poisson ratio decreases invariably with an increase in both the relative density and the effective confining pressure. The effect of the confining pressure on the Poisson ratio was found to become relatively more significant for fine-grained sand as compared with the coarse-grained sand. For a given material, at a particular value of sigma(3), the magnitude of the Poisson ratio decreases, almost in a linear fashion, with an increase in the value of maximum shear modulus (G(max)). The two widely used correlations in literature, providing the relationships among G(max), void ratio (e) and effective confining pressure (sigma(3)), applicable for angular granular materials, were found to compare reasonably well with the present experimental data for the fine- and medium-grained sands. However, for the coarse-grained sand, these correlations tend to overestimate the values of G(max).

Bootstrap and Fast Double Bootstrap Tests of Cointegration Rank with Financial Time Series

The likelihood ratio test of cointegration rank is the most widely used test for cointegration. Many studies have shown that its finite sample distribution is not well approximated by the limiting distribution. The article introduces and evaluates by Monte Carlo simulation experiments bootstrap and fast double bootstrap (FDB) algorithms for the likelihood ratio test. It finds that the performance of the bootstrap test is very good. The more sophisticated FDB produces a further improvement in cases where the performance of the asymptotic test is very unsatisfactory and the ordinary bootstrap does not work as well as it might. Furthermore, the Monte Carlo simulations provide a number of guidelines on when the bootstrap and FDB tests can be expected to work well. Finally, the tests are applied to US interest rates and international stock prices series. It is found that the asymptotic test tends to overestimate the cointegration rank, while the bootstrap and FDB tests choose the correct cointegration rank.

The Power of Bootstrap Tests of Cointegration Rank with Financial Time Series

Bootstrap likelihood ratio tests of cointegration rank are commonly used because they tend to have rejection probabilities that are closer to the nominal level than the rejection probabilities of the correspond- ing asymptotic tests. The e¤ect of bootstrapping the test on its power is largely unknown. We show that a new computationally inexpensive procedure can be applied to the estimation of the power function of the bootstrap test of cointegration rank. The bootstrap test is found to have a power function close to that of the level-adjusted asymp- totic test. The bootstrap test estimates the level-adjusted power of the asymptotic test highly accurately. The bootstrap test may have low power to reject the null hypothesis of cointegration rank zero, or underestimate the cointegration rank. An empirical application to Euribor interest rates is provided as an illustration of the findings.

Evaluating ILS and MLS Sites without Flight Tests

Instrument landing systems (ILS) and the upcoming microwave landing systems (MLS) are (or are planned to be) very important navigational aids at most major airports of the world. However, their performance is directly affected by the features of the site in which they are located. Currently, validation of the ILS performance is through costly and time-consuming experimental methods. This paper outlines a powerful and versatile analytical approach for performing the site evaluation, as an alternative to the experimental methods. The approach combines a multi-plate model for the terrain with a powerful and exhaustive ray-tracing technique and a versatile and accurate formulation for estimating the electromagnetic fields due to the array antenna in the presence of the terrain. It can model the effects of the undulation, the roughness and the impedance (depending on the soil type) of the terrain at the site. The results computed from the analytical method are compared with the actual measurements and good agreement is shown. Considerations for site effects on MLS are also outlined.

Effect of insertion of buffer-strip on the response of carbon-epoxy system in short beam tests

dThe work looks at the response to three-point loading of carbon-epoxy (CF-EP) composites with inserted buffer strip (BS) material. Short beam Shear tests were performed to study the load-deflection response as well as fracture features through macroscopy on the CF-EP system containing the interleaved PTFE-coated fabric material. Significant differences were noticed in the response of the CF-EP system to the bending process consequent to the architectural modification. It was inferred that introduction of small amounts of less adherent layers of material at specific locations causes a decrement in the load carrying capability. Further the number and the ease with which interface separation occurs is found to depend on the extent to which the inserted layer is present in either single or multiple layer positions.

An improved representation of vehicle incompatibility in frontal NCAP tests using a modified rigid barrier

With the objective of better understanding the significance of New Car Assessment Program (NCAP) tests conducted by the National Highway Traffic Safety Administration (NHTSA), head-on collisions between two identical cars of different sizes and between cars and a pickup truck are studied in the present paper using LS-DYNA models. Available finite element models of a compact car (Dodge Neon), midsize car (Dodge Intrepid), and pickup truck (Chevrolet C1500) are first improved and validated by comparing theanalysis-based vehicle deceleration pulses against corresponding NCAP crash test histories reported by NHTSA. In confirmation of prevalent perception, simulation-bascd results indicate that an NCAP test against a rigid barrier is a good representation of a collision between two similar cars approaching each other at a speed of 56.3 kmph (35 mph) both in terms of peak deceleration and intrusions. However, analyses carried out for collisions between two incompatible vehicles, such as an Intrepid or Neon against a C1500, point to the inability of the NCAP tests in representing the substantially higher intrusions in the front upper regions experienced by the cars, although peak decelerations in cars arc comparable to those observed in NCAP tests. In an attempt to improve the capability of a front NCAP test to better represent real-world crashes between incompatible vehicles, i.e., ones with contrasting ride height and lower body stiffness, two modified rigid barriers are studied. One of these barriers, which is of stepped geometry with a curved front face, leads to significantly improved correlation of intrusions in the upper regions of cars with respect to those yielded in the simulation of collisions between incompatible vehicles, together with the yielding of similar vehicle peak decelerations obtained in NCAP tests.

Tests for Cointegration Rank and the Initial Condition

Many economic events involve initial observations that substantially deviate from long-run steady state. Initial conditions of this type have been found to impact diversely on the power of univariate unit root tests, whereas the impact on multivariate tests is largely unknown. This paper investigates the impact of the initial condition on tests for cointegration rank. We compare the local power of the widely used likelihood ratio (LR) test with the local power of a test based on the eigenvalues of the companion matrix. We find that the power of the LR test is increasing in the magnitude of the initial condition, whereas the power of the other test is decreasing. The behaviour of the tests is investigated in an application to price convergence.

Parametrized tests of post-Newtonian theory using Advanced LIGO and Einstein Telescope

General relativity has very specific predictions for the gravitational waveforms from inspiralling compact binaries obtained using the post-Newtonian (PN) approximation. We investigate the extent to which the measurement of the PN coefficients, possible with the second generation gravitational-wave detectors such as the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and the third generation gravitational-wave detectors such as the Einstein Telescope (ET), could be used to test post-Newtonian theory and to put bounds on a subclass of parametrized-post-Einstein theories which differ from general relativity in a parametrized sense. We demonstrate this possibility by employing the best inspiralling waveform model for nonspinning compact binaries which is 3.5PN accurate in phase and 3PN in amplitude. Within the class of theories considered, Advanced LIGO can test the theory at 1.5PN and thus the leading tail term. Future observations of stellar mass black hole binaries by ET can test the consistency between the various PN coefficients in the gravitational-wave phasing over the mass range of 11-44M(circle dot). The choice of the lower frequency cutoff is important for testing post-Newtonian theory using the ET. The bias in the test arising from the assumption of nonspinning binaries is indicated.

Sediment Volume Tests for Expansive Soil Identification and Classification

Equilibrium sediment volume tests are conducted on field soils to classify them based on their degree of expansivity and/or to predict the liquid limit of soils. The present technical paper examines different equilibrium sediment volume tests, critically evaluating each of them. It discusses the settling behavior of fine-grained soils during the soil sediment formation to evolve a rationale for conducting the latest version of equilibrium sediment volume test. Probable limitations of equilibrium sediment volume test and the possible solution to overcome the same have also been indicated.

Direct tests of the entropic model of quasicrystals

Assuming an entropic origin for phason elasticity in quasicrystals, we derive predictions for the temperature dependence of grain-boundary structure and free energy, the nature of the elastic instability in these systems, and the behavior of sound damping near the instability. We believe that these will provide decisive tests of the entropic model for quasicrystals.

Continuity of plastic strain rate in stress relaxation tests

Stress relaxation testing is often utilised for determining whether athermal straining contributes to plastic flow; if plastic strain rate is continuous across the transition from tension to relaxation then plastic strain is fully thermally activated. This method was applied to an aged type 316 stainless steel tested in the temperature range 973–1123 K and to a high purity Al in the recrystallised annealed condition tested in the temperature range 274–417 K. The results indicated that plastic strain is thermally activated in these materials at these corresponding test temperatures. For Al, because of its high strain rate sensitivity, it was necessary to adopt a back extrapolation procedure to correct for the finite period that the crosshead requires to decelerate from the constant speed during tension to a dead stop for stress relaxation.