Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.

Stability of highly supersaturated vanadium electrolyte solution and characterization of precipitated phases for vanadium redox flow battery

The vanadium redox flow battery(VRFB)has been receiving great attention in recent years as one of the most viable energy storage technologies for large-scale applications.However,higher concentrations of vanadium species are required in the H_(2)O-H_(2)SO_(4) electrolyte in order to improve the VRFB energy density.This might lead to unwanted precipitation of vanadium compounds,whose nature has not been accurately characterized yet.For this purpose,this study reports the preparation ofⅤ^((Ⅱ)),ⅤV^((Ⅲ)),Ⅴ^((Ⅳ))andⅤ^((Ⅴ))supersaturated solutions in a 5 M H_(2)SO_(4)-H_(2)O electrolyte by an electrolytic method,from the only vanadium sulfate compound commercially available(VOSO_(4)).The precipitates obtained by ageing of the stirred solutions are representative of the solids that may form in a VRFB operated with such supersaturated solutions.The solid phases are identified using thermogravimetric analysis,X-ray diffraction and SEM.We report that dissolvedⅤ^((Ⅱ)),Ⅴ^((Ⅲ))andⅤ^((Ⅳ))species precipitate as crystals of VSO_(4),V_(2)(SO_(4))3 and VOSO_(4) hydrates and not in their anhydrous form;conversely V^((Ⅴ))precipitates as an amorphous V_(2) O_(5) oxide partially hydrated.The measured hydration degrees(respectively 1.5,9,3 and 0.26 mol of H_(2)O per mol of compound)might significantly affect the overall engineering of VRFB operating with high vanadium concentrations.

Effect of Valence Electron Structure on Temper Process and Hardness of the Supersaturated Carburized Layer

By measuring the hardness of carburized layer of a new type supersaturated carburizing steel （35Cr3SiMnMoV） at different temper temperature for 2 h, the relationship curve between the carburized layer hardness and the temper temperature is established. The result indicates that the hardness goes down firstly, then up and down, just like a wave consistent with the temperature increase. A secondary hardening peak appears at 570 ℃ or so. Based on Empirical Election Theory （EET） of Solids and Molecules, the valence electron structures （VESs） containing α-Fe-C, α-Fe-C-Me segregation structure units and carbide are calculated. The laws of temper process and hardness change with the temper temperature are explained, and the fact that reconstruction of θ-Fe3C is prior to that of special carbide at high tempering is analyzed with the phase structure formation factor, S, being taken into consideration. Therefore, the laws of temper process and hardness change of supersaturated carburized layer at different temper temperature can be traced back to valence electron structure （VES） level of alloy phase.

Mossbauer Spectroscopic Studies on a Supersaturated Solid Solution of Fe-Cu Formed by Mechanical Alloying

Mechanical alloying (MA) was employed to produce supersaturated solid solutions of Fe1-xCux,which is virtually immiscible under an equilibrium condition at ambjent temperature. The X-ray diffraction results show that the solutions formed in the concentration ranges of x≤0.1 5 and x≥0.40 are of bcc structure of iron and fcc structure of copper. respectively. For the region in between.however, the alloy obtained is a mixture of bcc plus fcc phases. The Mossbauer spectrum of the solid solution of a single phase could be fitted by two sub-spectra with hyperfine magnetic fields of 200 and 250 kOe. respectively. suggesting that there must exist two forms of coordination in the solution. While to fit the spectrum for the solution with mixed structu re. three Sub-spectra. including a spectrum of α-Fe, should be used. The variation of the Mossbauer spectra of Fe60Cu40 with milling time as well as annealing temperature was systematically studied. This may be ascribed to the changes of the number of nearest neighboring atoms of iron in the processes of formation and decomposition of the solid solution during milling and annealing

Nanometer Stripe Microstructure of Supersaturated Solid Solution in Fe-Cu Alloy

Strengthening due to precipitation of Cu in the a-Fe matrix is an important phenomenon utilized in the design of HSLA steels. In the present work, the microstructure of supersaturated solid solution in Fe-1.18%Cu binary alloy was investigated by means of high resolution electron microscopy. The results indicated that the solid solution was heterogeneous, there were lots of Cu atom clusters, which consisted of diffractive stripe microstructure similar to twin crystal. Orientation deviation was observed between two （110）o planes in diffractive stripes, which results in light and shade contrast. Furthermore, formation mechanisms of the nanometre stripe microstructure were discussed in terms of the interaction of Cu and Fe atoms in the Fe-Cu binary alloys.

Fe-Zn supersaturated solid solution prepared by mechanical alloying and laser sintering to accelerate degradation

The slow degration of iron limits its bone implant application.The solid solution of Zn in Fe is expected to accelerate the degradation.In this work,mechanical alloying(MA)was used to prepare Fe-Zn powder with supersaturated solid solution.MA significantly decreased the lamellar spacing between particles,thus reducing the diffusion distance of solution atoms.Moreover,it caused a number of crystalline defects,which further promoted the solution diffusion.Subsequently,the MA-processed powder was consolidated into Fe-Zn part by laser sintering,which involved a partial melting/rapid solidification mechanism and retained the original supersaturated solid solution.Results proved that the Fe-Zn alloy became more susceptible with a lowered corrosion potential,and thereby an accelerated corrosion rate of(0.112±0.013)mm/year.Furthermore,it also exhibited favorable cell behavior.This work highlighted the advantage of MA combined with laser sintering for the preparation of Fe-Zn implant with improved degradation performance.

Influence of total dissolved gas-supersaturated water on silver carp(Hypophthalmichthys molitrix)

Dam discharges over spillways are the main reason for the gas-supersaturated water generated in rivers.Local aquatic organisms,especially fish,readily develop gas bubble disease(GBD) in a river with total dissolved gas supersaturation(TDGS).Sometimes,fish will die after a specific exposure period,which negatively affects the biological equilibrium.In this study,the influence of TDGS on silver carp was explored.Silver carp were exposed to gas-supersaturated water with TDGS levels of 140%,135%,130%,125%,120%,and 110%to test the impact of TDGS.Some silver carp died when the TDGS level was 120%or higher,and all the silver carp exposed to a TDGS level of 140%died within10 h.In comparison with the Chinese sucker,Prenant's schizothoracin,and rock carp,silver carp seem less sensitive to TDGS.In addition,we tested the catalase(CAT) activity in the muscles and gills of silver carp after they were exposed to gas-supersaturated water with a TDGS level of140%.The CAT activity changed with time;it increased first and then decreased until it was lower than the initial CAT activity.The results of this study can provide basic data for developing a standard for environmental evaluation.

A CASE STUDY IN THE APPLICATION OF SUPERSATURATED DESIGNS TO COMPUTER EXPERIMENTS

Supersaturated design is essentially a fractional factorial design in which the number of potential effects is greater than the number of runs. In this article, the supersaturated design is applied to a computer experiment through an example of steady current circuit model problem. A uniform mixed-level supersaturated design and the centered quadratic regression model are used. This example shows that supersaturated design and quadratic regression modeling method are very effective for screening effects and building the predictor. They are not only useful in computer experiments but also in industrial and other scientific experiments.

Structural Imperfections Associated with Supersaturated Vacancies in an HPHT-Grown Diamond Single Crystal

A diamond single crystal, which was synthesized at a high temperature of 1570 K and a high pressure of 5.5 GPa in a Fe-Ni-C system, was directly and systematically examined by transmission electron microscopy (TEM). It is proposed that there exists a variety of imperfections such as dislocation loops, stacking faults, twins and stacking-fault tetrahedral in the diamond, which may be derived from the supersaturated vacancies generated during rapid cooling from high temperature. The formation process of the imperfections is discussed briefly.

Research on DTC System with Variable Flux for Switched Reluctance Motor

When switched reluctance motor(SRM)is in the status of the traditional direct torque control(DTC)system,due to the high saturation nonlinearity of the electromagnetic relationships of switched reluctance motors,the torque ripple and the stator phase current are larger.In order to resolve the above problems,through the analysis and deduction for SRM flux model and the influence of characteristics of flux and speed on torque ripple,this paper presents a variable-flux control strategy with the three closed-loop structure based on the critical flux supersaturated speed.And a DTC system of SRM with variable flux and three closed-loop is built up in Matlab/simulink.Moreover,the DSP hardware experiment platform based on the TMS320F2812 is established to validate the performance of the improved algorithm.The simulation and experimental results show that the new scheme has an obvious effect on torque ripple reduction,and the three-phase stator current is obviously reduced,which greatly reduces the stator winding copper consumption during the operation of SRM.Moreover,the improved system has good system stability.

COMPUTATION OF THE E(s^2) VALUES OF SOME E(s^2) OPTIMAL SUPERSATURATED DESIGNS

A supersaturated design is a design whose run size is not enough for estimating all the main effects represented by the columns of the design matrix. It is widely used in the preliminary stages of industrial statistics and other scientific experiments. In this paper, formulas for computing the E(s2) values of E(s2) optimal supersaturated designs with m = t(n - 1) ± e(e = 1 and 2) are given, and the accuracy and convenience of using these formulas are demonstrated by an example.

Effect of precipitation/re-dissolution processes from the supersaturated solution on the intestinal absorption of poorly water-soluble drugs

As one of the possible technologies to improve the oral absorption of poorly water-soluble drugs, supersaturable formulation, which enables to dissolve the drug to the higher concentration than their equilibrium solubility, is now attracting the attention (1)This include salt-formation, soliddispersion, co-crystallization or the use of amorphous form.Since supersaturation is a thermodynamically metastable state,supersaturated solution has a high potential to precipitate. Some pharmaceutical excipients.

Microanalysis of supersaturated gas release based on wall-attached bubbles

Supersaturation of dissolved gases in natural water,due to spillage from high dams and other factors,may cause fish mortality.In previous experiments,the dissipation coefficient has been used to denote the degassing process of total dissolved gas(TDG)saturation.These experiments mainly analyzed supersaturated TDG dissipation from a macroscopic view.To precisely clarify the mechanism of supersaturated TDG release,this study investigated bubble adsorption at a wall surface from a microscopic view.The experiment was conducted in a Plexiglas-wall container filled with supersaturated TDG water.A model that calculates the adsorption flux of supersaturated TDG by a solid wall,and helps describe construction for a contact angle at a three-phase intersection,was developed according to Young's equation.This model was used to investigate the formation process of bubbles adsorbed on a solid polymethyl methacrylate(PMMA)surface in supersaturated TDG water.The adsorption effect of a solid wall on TDG release was analyzed based on the experimental data.The modeling results were compared with observations under different wall area conditions,and it was found that TDG release tended to increase with wall area.This study helps improve our understanding of the mechanisms of supersaturated TDG release and provides an important theoretical method for accurate calculation of the release process.The adsorption flux model of the solid wall provides mitigation measures to combat the adverse effects of TDG supersaturation,which will be beneficial to the protection of aquatic organisms in hydropower-regulated rivers.

Stabilization mechanism of nitrazepam supersaturated state in nitrazepam/Eudragit~?EPO/saccharin solution revealed by NMR measurements

Aminoalkyl methacrylate copolymer,Eudragit?E PO(EPO),has been used as a polymeric carrier for solid dispersion to significantly enhance the drug dissolution.However,the improvement of the drug dissolution by the drug/EPO solid dispersion is limited only in acidic solution due to the pHdependant solubility of basic EPO with its tertiary amino group.We previously reported that the blending of saccharin(SAC)in the drug/EPO solid dispersion led to the supersaturation formation of drug even at neutral pH[1].

MORPHOLOGY OF MELT SPINNING SUPERSATURATED B2 NiAl

The morphology and structure of melt spinning Ni-33.6at% Al doped with B and RE were investigated.The results show that the alloy consists of L10 martensitic grains and L12 Ni3Al at the grain boundaries when it contains no B and RE.The addition of 0.11-0.31wt% B can suppress the martensitic transformation and Ni3Al separation at the boundaries,and a supersaturated B2 single phase NiAl is obtained.The addition of 0.05wt% RE can eliminate Ni3Al precipitated at the boundaries and get complete martensite,but 0.2-0.8wt% RE addition can suppress the martensitic transformation, and supersaturated B2 single phase NiAl is obtained.The formation mechanism of supersaturated B2 single phase NiAl has been analyzed.

Damping Property of Supersaturated ZnA127Ce Alloy during Natural Aging

The microstructures and damping property of supersaturated ZnA127Ce alloy during natural aging have been investigated. H-800 TEM was mainly used to research the microstructures. The relationship between microstructure and damping property was primarily studied. The results showed that solution plus natural aging was the best heat treatment, which could improve the damping property. Both continuous precipitation and cellular reaction occurred during the aging. Continuous precipitation follows the sequence: β→spherical GP zones→elliptical GP zones→intermediate phase R→n. The cellular reaction can be written as follows:β→a+n+ε.

Effects of Temperature on the Deposition Rate of Supersaturated Silicic Acid on Ca-type Bentonite Tsuyoshi Sasagawa, Taiji Chida and Yuichi Niibori

Na-type bentonite is commonly used as a tunnel backfilling material to prevent groundwater and radionuclide migration during the construction of a geological disposal system for high-level radioactive waste in Japan. However, host rock fractures with strong water flow can develop groundwater paths in the backfilling material. Especially, the alteration to Ca-type bentonite causes degradation of the barrier performance and accelerates the development of groundwater paths. Additionally, using cementitious materials gradually changes pH between 13 and 8. High alkaline groundwater results in high solubility of silicic acid; therefore, silicic acid is eluted from the host rock. Downstream, in the low alkaline area, the groundwater becomes supersaturated in silicic acid. This acid is deposited on Ca-type bentonite, thus leading to the clogging of the groundwater paths. In the present study, we investigate the silicic acid deposition rate on Ca-type bentonite under 288-323 K for depths greater or equal to 500 m. The results indicate that temperature does not affect the silicic acid deposition rate up to 323 K. However, in this temperature range, the deposition of silicic acid on Ca-type bentonite in backfilled tunnels results in clogging of the flow paths.

Evolution of nonmetallic inclusions in 80-t 9CrMoCoB large-scale ingots during electroslag remelting process

In combination with theoretical calculations,experiments were conducted to investigate the evolution behavior of nonmetallic inclusions(NMIs)during the manufacture of large-scale heat-resistant steel ingots using 9CrMoCoB heat-resistant steel and CaF_(2)–CaO–Al_(2)O_(3)–SiO_(2)–B_(2)O_(3)electroslag remelting(ESR)-type slag in an 80-t industrial ESR furnace.The main types of NMI in the consumable electrode comprised pure alumina,a multiphase oxide consisting of an Al_(2)O_(3)core and liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO shell,and M_(23)C_(6)carbides with an MnS core.The Al_(2)O_(3)and MnS inclusions had higher precipitation temperatures than the M_(23)C_(6)-type carbide under equilibrium and nonequilibrium solidification processes.Therefore,inclusions can act as nucleation sites for carbide layer precipitation.The ESR process completely removed the liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO oxide and MnS inclusion with a carbide shell,and only the Al_(2)O_(3)inclusions and Al_(2)O_(3)core with a carbide shell occupied the remelted ingot.The M_(23)C_(6)-type carbides in steel were determined as Cr_(23)C_(6)based on the analysis of transmission electron microscopy results.The substitution of Cr with W,Fe,or/and Mo in the Cr_(23)C_(6)lattice caused slight changes in the lattice parameter of the Cr_(23)C_(6)carbide.Therefore,Cr_(21.34)Fe_(1.66)C_(6),(Cr_(19)W_(4)C_(6),Cr_(18.4)Mo_(4.6)C_(6),and Cr_(16)Fe_(5)Mo_(2)C_(6)can match the fraction pattern of Cr_(23)C_(6)carbide.The Al_(2)O_(3)inclusions in the remelted ingot formed due to the reduction of CaO,SiO_(2),and MnO components in the liquid inclusion.The increased Al content in liquid steel or the higher supersaturation degree of Al_(2)O_(3)precipitation in the remelted ingot than that in the electrode can be attributed to the evaporation of CaF_(2)and the increase in CaO content in the ESR-type slag.

Computational Fluid Dynamics Approach to the Effect of Mixing and Draft Tube on the Precipitation of Barium Sulfate in a Continuous Stirred Tank

The effect of mixing on the precipitation of barium sulfate in a continuous stirred tank is simulated numerically with different feeding location, feed concentration, impeller speed and residence time through solving the standard momentum and mass transport equations in combination with the moment equations for crystal population balance. The numerical method was validated with the literature data. The simulation results including the distribution of the local supersaturation ratio distribution in the precipitator, mean crystal size and coefficient of variation under different operating conditions compared well with experimental data in the literature. The effect of the presence of a draft tube on precipitation were also investigated, and it is suggested that the installation of a draft tube increased the mean crystal size, in general agreement with experimental work in the literature.

INTERACTION OF PRECIPITATION AND RECRYSTALLIZATION IN RAPIDLY SOLIDIFIED Cu-Cr-Zr-Mg ALLOY

The recrystallization process of a rapidly solidified Cu-Cr-Zr-Mg alloy during its aging was investigate experimentally. It was found that (1) upon aging, the precipitation process takes place prior to recrystallization for the cold-deformed Cu-Cr-Zr-Mg alloy produced by rapid solidification, and the precipitates have a restrained effect on the following recrystallization process; (2) the hindrance of the dispersed fine precipitates to the common recrystallization leads to the simultaneous in situ and discontinuous recrystallization; (3) the resolution of the precipitates in the front of migrating grain boundaries takes place during the nucleation and growth of recrystallization, which results in a supersaturation in the recrystallized zones, while the re-precipitation of the supersaturated solute atoms in vacancies further increases the dispersion hardening effect.