Production of Carbopol® 974P and Carbopol® 971P Pellets by Extrusion‐Spheronization: Optimization of the Processing Parameters and Water Content

Pellets obtained by extrusion‐spheronization represent multiparticulate dosage forms whose interest in intestinal drug delivery can be potentiated and targeted through bioadhesive properties. However, adhesion itself makes the process difficult or even impossible. The problem of tackiness encountered with bioadhesive wet masses was previously eliminated by the use of electrolytes such as CaCl₂. This approach is known to reduce the viscosity of polyacrylic acids by disturbing the interactions between carboxylate groups on adjacent polymer molecules, thereby decreasing their bioadhesive properties. The present study aimed at producing pellets containing carbomers without addition of electrolytes in order to maintain their bioadhesive potentiality at its maximum. Carbopol® 974P (10%, 15% and 20%) and Carbopol® 971P (10%) were used in combination with Avicel® PH101. The extrusion speed (30, 45, 60, 90, and 150 rpm), spheronizer speed (350, 700, 960, 1000, and 1300 rpm), spheronization time (5, 10, 15, and 20 minutes) and amount of water (45%, 50%, 54%, and 58%) were optimized in order to obtain the highest yield of spherical pellets ranging 710–1000 µm in diameter. For pellets containing 10%, 15% Carbopol® 974P or 10% Carbopol® 971P and 45% water content, 30 rpm extrusion speed, 960 rpm, and 10 minutes spheronization speed and time led to the highest yields and sphericities, respectively, 72% and 0.91, 67% and 0.78, and 76% and 0.80. Production of pellets with 20% Carbopol® 974P could be achieved through the increase of the water content up to 58% and implementation of 30 rpm extrusion speed, 1300 rpm, and 10 minutes spheronization speed and time. The yield and sphericity were 42% and 0.78 respectively.     

Sustained-release of Cyclosporin A pellets: preparation,in vitro release,pharmacokinetic studies and in vitro–in vivo correlation in beagle dogs

The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro–in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18?±?0.17?g/100?g), good stability and showed a sustained-release effect. The C_max, T_max and AUC_0–24 of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22?±?15.99?ng/ml, 6?±?0?h and 3205.00?±?149.55?ng·h/ml, respectively. Compared with Neoral®, CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24?h. The relative bioavailability of CsA pellets was 125.68?±?5.37% that of Neoral®. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24?h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC.     

Influence of mineral phase in mineralization of a biocomposite containing chitosan,demineralized bone matrix and bone ash—in vitro study

A resorbable composite which acts as a active barrier in guided bone regeneration was fabricated using chitosan, demineralized bone matrix and bone ash. Its potential to form bone like apatite in simulated body fluid was assessed in this study. The mechanical strength of these composites was correlated with bone ash ratios and composites with better tensile strength were studied for their acellular bioactivity by incubating in simulated body fluid for 21 days. Composites without bone ash did not show acellular bioactivity which was confirmed by thermogravimetric analysis. In case of biocomposites with bone ash, there was an increase in residual weight indicating the mineralization of the composite. The composite containing bone ash has shown the peaks related to phosphate vibrations in its Fourier-transform infrared spectrum. Scanning micrographs revealed formation of apatite like crystals on its surface. Ca/P ratio was found to be 1·7 which is nearer to that of natural bone. Thus, prepared composites can be used as resorbable biocomposite in maxillofacial and oral defects.     

Roles of detwinning in strain hardening and ultimate elongation in extruded Mg–3Al–1Zn alloy

Abstract

For extruded magnesium alloy, prior compression along extrusion direction has great influences in the flow stress during subsequent tension. Detwinning plays an important role for these influences. In the present study, the effects of different prestrains on strain hardening behaviour during subsequent tension were examined in an extruded magnesium alloy AZ31. The results showed that the existence of detwinning decreased the tensile yield stress. Samples with different prestrains exhibited different strain hardening behaviour during subsequent tension. The reorientation due to detwinning had a great effect on strain hardening during tension. In addition, the effect of detwinning on ultimate elongation was investigated. The results showed that the sample with higher prestrain always has higher ultimate elongation due to the contribution of detwinning on macroscopic strain.     

Use and effectiveness of health impact assessment in the energy and natural resources sector in the United States, 2007 – 2016

Decisions made in the energy and natural resources sector can affect public health. This report reviews the characteristics and assesses the effectiveness of health impact assessments (HIAs) conducted in this sector. A total of 30 HIAs conducted in 14 states in the United States were identified using a targeted literature search. Five HIAs illustrative of the different source and sub-sector categories, and with identifiable impacts on decision-making processes were selected for review. An existing conceptual framework (Wismar) was used to assess the effectiveness of the five selected HIAs on decision-making related to non-renewable energy, renewable energy, mining, and energy conservation. The 30 HIAs were performed for a variety of projects and assessed health impacts ranging from metabolic disorders to community livability. Eight of the 30 reports were incorporated into environmental impact assessments. All five selected HIAs were generally effective and raised awareness of the health effects of the projects being assessed; four were directly effective and led to changes in final project decisions. Their variable effectiveness may be related to the extent of community engagement and consideration of equity issues, differences in the details and quality of monitoring and evaluation plans devised as part of the HIA process, and whether the outcomes of monitoring and evaluation are reported.     

Development,optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box–Behnken experimental design

Objective: The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs).

Methods: Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett–Burman design (PBD) followed by Box–Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP.

Results: The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39?±?1.82?nm, apparent drug content (ADC) of 72.06?±?0.86%, and zeta potential (ZP) of ?13.91?±?1.21?mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48?h and followed Korsmeyer–Peppas release kinetic model.

Conclusions: A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.     

Use of the Bohm’s formula and its analogues in probe diagnostics

Simple algorithms are developed to proceed the probe characteristics in a number of limiting regimes when the characteristic probe size, r _p, is relatively large (r _p > 10³rD). It relates both to steady plasmas and to movement with the directed velocity, u. We consider the cases of collision-free (the Knudsen number, Kn?1) and collisional (Kn?1) plasmas. The majority of the proposed algorithms are tested in practice and confirm their reliability.     

Localization and Registration of Three-Dimensional Objects in Space-Where are the Limits?

We discuss the accuracy limits for the localization of surfaces in three-dimensional (3-D) space. Such a localization is necessary for the registration of different views of an object, taken by 3-D sensors from several directions. A quantitative analysis shows that the lateral localization accuracy of a small surface area is proportional to the local curvature of the surface. This confirms the intuitive conjecture that our visual system performs localization of 3-D objects via sharp features. The longitudinal localization accuracy depends only on the noise of the data and is usually much better than the lateral localization accuracy, suggesting that surfaces are to be registered only along the longitudinal directions.     

P, ρ, T-properties and phase equilibria in the water-n-hexane system with a low content of water

Using a piezometer of constant volume, we determined experimentally the P, ρ, and T properties and the phase equilibria for the binary water-n-hexane mixtures with 0.04, 0.05, 0.06, and 0.0673 mass fraction of H₂O over the density range of 0.067–0.607 g/cm³, temperature range of 380–680 K, at pressures up to 60 MPa. The equilibrium lines of the liquid-liquid and liquid-gas transition have been determined. The three-phase line, the line of the azeotrope, and the lower branch of the critical line (all lines are joined at the upper finite critical point) have been plotted in the work.     

Hot tensile behavior of an extruded Al–Zn–Mg–Cu alloy in the solid and in the semi-solid state

This is the first reported research into the tensile behavior of as-deformed Al–Zn–Mg–Cu alloy in the semi-solid state. Tensile tests of extruded 7075 aluminium alloy were carried out in the high temperature solid and semi-solid states. Based on the tensile results and microstructural examination, the tensile behavior can be divided into three stages according to the effect of liquid: one behaves in predominantly ductile character between 400 and about 520 °C (f_l ∼ 0.31%), one is governed by both of solid and liquid between 520 and 550 °C (f_l ∼ 2%), and almost completely dominated by liquid above ∼550 °C. A brittle temperature range (519–550 °C) is proposed, in which the as-deformed Al–Zn–Mg–Cu alloy exhibits large crack probability. An equation based on ultimate tensile stress and temperature is proposed.     

Use of age–period–cohort models to estimate effects of vehicle age,year of crash and year of vehicle manufacture on driver injury and fatality rates in single vehicle crashes in New South Wales, 2003–2010

A novel application of age–period–cohort methods are used to explain changes in vehicle based crash rates in New South Wales, Australia over the period 2003–2010. Models are developed using vehicle age, crash period and vehicle cohort to explain changes in the rate of single vehicle driver fatalities and injuries in vehicles less than 13 years of age. Large declines in risk are associated with vehicle cohorts built after about 1996. The decline in risk appears to have accelerated to 12 percent per vehicle cohort year for cohorts since 2004. Within each cohort, the risk of crashing appears to be a minimum at two years of age and increases as the vehicle ages beyond this. Period effects (i.e., other road safety measures) between 2003 and 2010 appear to have contributed to declines of up to about two percent per annum to the driver-fatality single vehicle crash rate, and possibly only negligible improvements to the driver-injury single vehicle crash rate. Vehicle improvements appear to have been responsible for a decline in per-vehicle crash risk of at least three percent per calendar year for both severity levels over the same period. Given the decline in risk associated with more recent vehicle cohorts and the dynamics of fleet turnover, continued declines in per-vehicle crash risk over coming years are almost certain.     

Central composite rotatable design for optimization of budesonide-loaded cross-linked chitosan–dextran sulfate nanodispersion: characterization,in vitro diffusion and aerodynamic study

Budesonide is a BCS class II drug with low water solubility (0.045?mg/mL) and low oral bioavailability (6–8%) due to high first pass effect. The aim is to prepare cross-linked chitosan–dextran sulfate nanoparticles and/or nanodispersion. Nebulizable cross-linked nanodispersion was prepared by the solvent evaporation technique and characterized through XRPD, FTIR, mean particle size (MPS), polydispersity index (PDI), zeta potential (ZP), drug loading, entrapment efficiency, SEM, % production yield, in vitro diffusion, aerodynamic and stability study. The optimization of formulation was done by using central composite rotatable design to study the effect of independent variables, concentration of chitosan (X1) and concentration dextran sulfate (X2) on the dependent variables, MPS (Y1), drug loading (Y2) and % CDR (% cumulative drug release) (Y3). The MPS, PDI, and ZP of budesonide-loaded nanoparticles were 160.8?±?0.27?nm, 0.36?±?0.04, and 13?±?0.894?mV, respectively. The percent drug loading of all the batches was found in range of 10–16%. The emitted drug in target region (alveoli) was measured by using HPLC and it was found to be 18.26%. It was found that, nanodispersion had the optimum in vitro aerodynamic behavior. Stability study results showed no significant change in MPS, PDI, ZP, and % CDR after three month storage. In conclusion, cross-linked chitosan–dextran sulfate nanoparticles had properties suitable for nebulizable dispersion of increased drug loading, in vitro drug release and avoiding the first pass effect.     

Crystal Structure of (Ti,Mo)12P7and Refined Phase Equilibria in the Ti–Mo–P System

A new ternary compound of composition Ti_3.8Mo_8.2P_7.0 was identified, and its structure was determined by single-crystal x-ray diffraction: sp. gr. P6¯, a= 1.67821(6) nm, c= 0.33196(2) nm; R _F = 0.073 and R _w = 0.078 for 1359 independent reflections with F _hkl > 4(F _hkl). The phase equilibria in the Ti–Mo–P system were refined in the region 0–25 mol % Ti and 33–40 mol % P.     

Role of Alloying Elements P, Cu in Liquid Phase Sintering of Short Cast Iron Fiber

The effects of alloying elements P and Cu on the sintering process and mechanical properties of short cast iron fiber compact have been studied. The experimental results show that the sintering can be enhanced obviously by addition of phosphorus. The radial crush strength of sintered compacts increases with P content up to 0.15%, but when P content is over 0.15%,eutectics formed at the interfaces of fibers cause the decrease in strength and quasi-cleavage fracture of the sintered compact. Addition of Cu could not only reduce the volume shrinkage effectively, but also increase the strength and hardness of the sintered compact.     

National Verification Regulations and Calibration Specifications of Measuring Instruments of P. R. China in 2006

2006 No.78 General Administration of Quality Supervision, Inspection and Quarantine of P. R. China has approved the following 24 national measuring verification regulations in 2006 and publicize now.     

First-Principle Investigations of Structural,Electronic, and Half-Metallic Ferromagnetic Properties in In1−xTM x P (TM = Cr,Mn)

First-principle calculations within the framework of density functional theory are employed to study the structural, electronic, and half-metallic ferromagnetic properties of In_1?x (TM) _x P (TM = Cr, Mn) at concentrations (x = 0.0625, 0.125, 0.25)of transition metal in zinc blende phase. The investigations of electronic and magnetic properties indicate that In_1?xTM _x P (TM = Cr, Mn) at x = 0.0625, 0.125, and 0.25 are half-metallic ferromagnets with 100 % magnetic spin polarization. On the one hand, the total magnetization is an integer Bohr magneton of 3 μ _B and 4 μ _B for In_1?xCr _x P and In_1?xMn _x P, respectively, which confirms the half-metallic feature of In_1?xTM _x P compounds. On the other hand, the densities of states of majority-spin states show that the large hybridization between 3p (P) and 3d (TM) partially filled states dominates the gap, which stabilizes the ferromagnetic state configuration associated with double-exchange mechanism. The band structures depict that half-metallic gap at x = 0.0625 is 0.404 eV for In_1?xCr _x P which is higher than 0.125 eV for In_1?xMn _x P. Therefore, the largest half-metallic gap in In_1?xCr _x P at low concentration x = 0.0625 reveals that Cr-doped InP seem to be a more potential candidate than that Mn-doped InP for spin injection applications in the field of spintronic devices.     

Synthesis,characterization and in vitro bioactivity of sol-gel-derived SiO2–CaO–P2O5–MgO bioglass

In this study, the synthesis of SiO₂–CaO–P₂O₅–MgO bioactive glass was performed by the sol-gel method. Sol-gel-derived bioglass material was produced both in powder and in discs form by uniaxial pressing, followed by sintering at 700 °C. The obtained material was evaluated by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), thermal gravimetric analysis (TGA) and differential scanning caloremetry (DSC) analyses. The biocompatibility evaluation of the formed glass was assessed through in vitro cell culture [alkaline phosphatase (AP) activity of osteoblasts] experiments and immersion studies in simulated body fluid (SBF) for different time intervals while monitoring the pH changes and the concentration of calcium, phosphorus and magnesium in the SBF medium. The SEM, XRD and FTIR studies were conducted before and after soaking of the material in SBF. At first, an amorphous calcium phosphate was formed; after 7 days this surface consisted of deposited crystalline apatite. The present investigation also revealed that the sol-gel derived quaternary bioglass system has the ability to support the growth of human fetal osteoblastic cells (hFOB 1.19). Finally, this material proved to be non-toxic and compatible for the proposed work in segmental defects in the goat model in vivo.