Sustainable Stabilizer-Free Nanoparticle Formulations of Valsartan Using Eudragit® RLPO

The bioavailability of the antihypertensive drug valsartan can be enhanced by various microencapsulation methods. In the present investigation, valsartan-loaded polymeric nanoparticles were manufactured from Eudragit® RLPO using an emulsion–solvent evaporation method. Polyvinyl alcohol (PVA) was found to be a suitable stabilizer for the nanoparticles, resulting in a monodisperse colloid system ranging in size between 148 nm and 162 nm. Additionally, a high encapsulation efficiency (96.4%) was observed. However, due to the quaternary ammonium groups of Eudragit® RLPO, the stabilization of the dispersion could be achieved in the absence of PVA as well. The nanoparticles were reduced in size (by 22%) and exhibited similar encapsulation efficiencies (96.4%). This more cost-effective and sustainable production method reduces the use of excipients and their expected emission into the environment. The drug release from valsartan-loaded nanoparticles was evaluated in a two-stage biorelevant dissolution set-up, leading to the rapid dissolution of valsartan in a simulated intestinal medium. In silico simulations using a model validated previously indicate a potential dose reduction of 60–70% compared to existing drug products. This further reduces the expected emission of the ecotoxic compound into the environment.

The Reactivity of New Zealand Ilmenites

<p>The dissolution of West Coast, South Island, New Zealand ilmenite in acid solutions was studied under a variety of conditions, including concentrations approaching those used industrially. The major dissolution medium considered was hydrochloric acid (1-->10 M), at temperatures of 50-->80 degrees C. The series of experiments undertaken souqht to establish the factors affecting the reactivity of the ilmenite samples. Concentrations of dissolved components of the ilmenite were followed by Atomic Absorption spectrometry and the structure and composition of the residual ilmenite was examined by X-ray powder diffraction, X-ray fluorescence, electron microprobe and scanning electron microscopy. Evidence for the rapid dissolution of an iron-rich surface phase was observed, but the dominant feature of early reaction is selective attack along zones parallel to the basal plane of the ilmenite structure. After the initial phase of rapid dissolution, reaction rate declines and all extended period of concentration/time linearity follows. This decline in rate appears to relate to polymerisation and. transport of dissolved titanium within the porous solid. The addition of phosphate and fluoride to the system, has been shown to seriously affect the properties and transport of dissolved titanium. The effects of other interfering reagents such as additional titanium and iron were also considered. The observed behaviour of these ilmenites in dissolution, was related to the pattern of natural weathering identified in other ilmenite concentrates The structure and composition of a range of these materials was examined by X-ray diffraction, Electron microprobe and Mossbauer spectroscopy.</p>

The Reactivity of New Zealand Ilmenites

<p>The dissolution of West Coast, South Island, New Zealand ilmenite in acid solutions was studied under a variety of conditions, including concentrations approaching those used industrially. The major dissolution medium considered was hydrochloric acid (1-->10 M), at temperatures of 50-->80 degrees C. The series of experiments undertaken souqht to establish the factors affecting the reactivity of the ilmenite samples. Concentrations of dissolved components of the ilmenite were followed by Atomic Absorption spectrometry and the structure and composition of the residual ilmenite was examined by X-ray powder diffraction, X-ray fluorescence, electron microprobe and scanning electron microscopy. Evidence for the rapid dissolution of an iron-rich surface phase was observed, but the dominant feature of early reaction is selective attack along zones parallel to the basal plane of the ilmenite structure. After the initial phase of rapid dissolution, reaction rate declines and all extended period of concentration/time linearity follows. This decline in rate appears to relate to polymerisation and. transport of dissolved titanium within the porous solid. The addition of phosphate and fluoride to the system, has been shown to seriously affect the properties and transport of dissolved titanium. The effects of other interfering reagents such as additional titanium and iron were also considered. The observed behaviour of these ilmenites in dissolution, was related to the pattern of natural weathering identified in other ilmenite concentrates The structure and composition of a range of these materials was examined by X-ray diffraction, Electron microprobe and Mossbauer spectroscopy.</p>

Modeling and Simulation of Non-Uniform Electrolytic Machining Based on Cellular Automata

Porous microstructure is a common surface morphology that is widely used in antifouling, drag reduction, adsorption, and other applications. In this paper, the lattice gas automata (LGA) method was used to simulate the non-uniform electrochemical machining of porous structure at the mesoscopic level. In a cellular space, the metal and the electrolyte were separated into orderly grids, the migration of corrosive particles was determined by an electric field, and the influences of the concentration gradient and corrosion products were considered. It was found that different pore morphologies were formed due to the competition between dissolution and diffusion. When the voltage was low, diffusion was sufficient, and no deposit was formed at the bottom of the pore. The pore grew faster along the depth and attained a cylindrical shape with a large depth-to-diameter ratio. As the voltage increased, the dissolution rates in all directions were the same; therefore, the pore became approximately spherical. When the voltage continued to increase, corrosion products were not discharged in time due to the rapid dissolution rate. Consequently, a sedimentary layer was formed at the bottom of the pore and hindered further dissolution. In turn, a disc-shaped pore with secondary pores was formed. The obtained simulation results were verified by experimental findings. This study revealed the causes of different morphologies of pores, which has certain guiding significance for non-uniform electrochemical machining.

Metastable phases and macroheterogeneous composites

The way to control the interfacial reactions that processes during infiltration of macroheterogeneous composite materials is suggested. The idea is to combine the stable and metastable phases in the filler’s structure which dissolves at a different rate in the molten binder. To prove this approach, the structure and gas-abrasive wear of macroheterogeneous composite materials with Cu–20Ni–20Mn binder reinforced by Fe–(9.0–10.0)B–(0.01-0.2)C filler (in wt. %) cooled at 10–20 K/s or 103–104 K/s are studied. It is shown that the wear resistance of the investigated composite materials can be enhanced by accelerating interfacial reactions between the filler and the molten binder. Therefore, the composite materials produced from a rapidly cooled Fe–B–C filler show a higher resistance to gas-abrasive wear due to formation of Fe–Fe2(B,C) metastable eutectics in its structure. This eutectics crystallizes under metastable phase diagram due to the suppression of stable Fe2(B,C) phase formation and saturation of the rest of liquid by iron in the filler cooled at 103–104 K/s. As a result of rapid dissolution of the eutectics in the molten binder during infiltration, the strong adhesion at the interfaces of the composite materials is achieved which prevents the filler from spalling out under the impacts of abrasive.

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs

Background Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. Results The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). Conclusions These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

Optical Monitoring of the Biodegradation of Porous and Solid Silicon Nanoparticles

Silicon nanoparticles (SiNP) are currently of great interest, especially in biomedicine, because of their unique physicochemical properties combined with biodegradability. SiNPs can be obtained in various ways and can have either a non-porous solid (sol-) or porous (por-) structure. In this work, we carry out detailed optical monitoring of sol- and por-SiNP biodegradation using Raman and photoluminescence (PL) micro-spectroscopy. SiNPs were obtained by ultrasound grinding of sol- or por-silicon nanowires, created by silver-assisted chemical etching of crystalline Si with different doping levels. In this case, sol-SiNPs consist of nanocrystals 30 nm in size, while por-SiNPs consist of small 3 nm nanocrystals and 16 nm pores. Both SiNPs show low in vitro cytotoxicity towards MCF-7 and HEK293T cells up to 800 μg/mL. The appearance of the F-band (blue–yellow) PL, as well as a decrease in the intensity of the Raman signal, indicate the gradual dissolution of the sol-SiNPs during 20 days of incubation. At the same time, the rapid dissolution of por-SiNP within 24 h is identified by the quenching of their S-band (red) PL and the disappearance of the Raman signal. The obtained results are important for development of intelligent biodegradable drug delivery systems based on SiNPs.

The Enhancement of Enargite Dissolution by Sodium Hypochlorite in Ammoniacal Solutions

The dissolution of both copper and arsenic from a copper concentrate was investigated in oxidative ammonia/ammonium solutions at moderate temperatures and atmospheric pressure. The main parameters studied were temperature, pH, concentrations of different ammonia salts, the presence of sodium hypochlorite, pretreatment with sodium chloride, and curing period. In all ammoniacal solutions studied, increasing the temperature enhanced the dissolution of copper, but the dissolution of arsenic remained marginal. Mixing the copper concentrate with sodium chloride and leaving it to rest for 72 h before leaching in ammoniacal solutions significantly increased the dissolution of copper and slightly increased the dissolution of arsenic from the concentrate. A maximum of 35% of Cu and 3.3% of As were extracted when ammonium carbonate was used as the lixiviant. The results show relatively rapid dissolution of the concentrate with the addition of sodium hypochlorite in ammonium carbonate solution, achieving a dissolution of up to 50% and 25% of copper and arsenic, respectively. A copper dissolution with a non-linear regression model was proposed, considering the effect of NaClO and NH4Cl at 25 °C. These findings highlight the importance of using the correct anionic ligands for the ammonium ions and temperature to obtain a high dissolution of copper or arsenic. The results also showed that the curing time of the packed bed before the commencement of leaching appeared to be an important parameter to enhance the dissolution of copper and leave the arsenic in the residues.

Nanocrystal-Loaded Micelles for the Enhanced In Vivo Circulation of Docetaxel

Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.