An analysis of the biopharmaceutical behaviour of proton pump inhibitors with different physicochemical properties.

At present, little information on the biopharmaceutical behaviour of proton pump inhibitors (PPIs) describing their absorption and biodistribution in vivo has been reported because the extreme instability of PPIs in the gastrointestinal environment makes it difficult to analyze such behaviour. In this work, a modified rat in situ intestinal perfusion model was employed to investigate absorption in the gastrointestinal tract and subsequent biodistribution of several PPIs (ilaprazole, esomeprazole and rabeprazole), which have different physicochemical properties. Our data indicated that PPIs exhibited significantly enhanced absorption rates in the whole intestine, including the duodenum, jejunum, ileum and colon, corresponding to the increase in the oil-water partition coefficient (LogP). PPIs and corresponding salt types showed no obvious differences in absorption, implying that solubility changes in the PPI have little effect on its absorption in the gastrointestinal tract. Among these PPIs, ilaprazole presented a more stable intestinal absorption behaviour, as well as more distribution and longer residence time in the stomach by HPLC-MS/MS analysis and radioactivity counts after 14C radiolabelling. These results may be useful information for PPI optimization and oral formulation design.

Distribution and sources of ordinary monomeric and emerging oligomeric organophosphorus flame retardants in Haihe Basin, China.

With the banning of poly-brominated diphenyl ethers, organophosphorus flame retardants (OPFRs) have gained great development space as their alternatives. In this study, the concentration and partition of nine ordinary monomeric OPFRs and two emerging oligomeric OPFRs (Resorcinol bis(diphenyl phosphate) (RDP) and bisphenol A bis(diphenyl phosphate) (BDP) in the Haihe Basin of China were studied, and their possible sources were analyzed. The Æ©OPFRs in the surface water, sediments and suspended particulate matters (SPMs) in Haihe Basin were 80.1-777 ng/L, 18.9-86.5 ng/g dw and 6.40-234 ng/g dw, respectively. The detection frequencies of both oligomeric OPFRs exceeded 85%, suggesting their environmental contamination was widespread. The mean concentrations of RDP and BDP were 2.09 and 6.03 ng/L in the surface water, 0.91 and 5.09 ng/g dw in the sediments, 1.08 and 2.61 ng/g dw in SPMs, respectively. With Cl-OPFRs being predominant in all the three media, the proportions of alkyl-OPFRs, aryl-OPFRs, and oligomeric OPFRs in the sediments and SPMs were remarkably higher than those in surface water, suggesting that non-halogenated OPFRs preferred to distribute in solid phases. The water-sediment/SPM partition coefficients, logKoc, of the OPFRs were calculated based on the paired samples. The logKoc values of RDP and BDP were reported for the first time, and their logKoc water-sediment were 4.36 ± 0.47 and 4.76 ± 0.25 and their logKoc water-SPM were 3.77 ± 0.45 and 4.00 ± 0.47, respectively. The obtained logKoc values were correlated with their octanol-water partition coefficient (logKow) significantly. It suggested that their partition to sediment or SPM was dominated by hydrophobic interaction. Principal component analysis indicated that the emissions from manufacturing plants and airport operation might be two important sources of OPFRs in the Haihe Basin of China.

Probing mechanisms for bioaccumulation of perfluoroalkyl acids in carp (Cyprinus carpio): Impacts of protein binding affinities and elimination pathways.

With regulations on the manufacture and usage of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS) and related compounds, short-chain perfluoroalkyl acids (PFAAs) are increasingly being used as alternatives. However, there are limited studies on their bioaccumulation mechanisms, especially for short-chain PFAAs. In this study, we examined the binding affinity of PFAAs with fish serum proteins and tissue distributions of perfluoroalkyl carboxylates (C7-C11 PFCAs) and perfluoroalkyl sulfonates (C4, C6, and C8 PFSAs) in carp (Cyprinus carpio), including the isomers of PFOS and perfluorohexane sulfonate (PFHxS). For both PFCAs and PFSAs, the fish serum protein binding constant (KA) and bioconcentration factor (BCF) increased with an increase in the carbon chain length. PFHxS (C6 PFSA) had a much higher KA but displayed a much lower BCF than those of C7-C11 PFCAs. It indicated that not only fish blood proteins, but also other proteins in the liver and kidney, mediated the accumulation of PFAAs in fish. The lowest concentration ratios of PFHxS in liver to blood and in kidney to blood suggested that it could not be effectively transported to liver and kidney by fatty acid binding proteins and organic anion transporters. PFOS and PFHxS displayed different elimination pathways, although their linear (n-) isomers were accumulated more in fish than the corresponding branched (br-) isomers. The n-PFOS was eliminated more via the feces but br-PFOS was eliminated more via the urine; while the opposite trend was observed for PFHxS isomers.

In vitro and in vivo evaluation of a posaconazole-sulfobutyl ether-ß-cyclodextrin inclusion complex.

Posaconazole (PCZ) is a triazole antifungal agent with an extended spectrum of antifungal activity. It is approved for the prophylaxis of invasive fungal infections in patients with neutropenia or in hematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft-vs-host disease, and for the treatment of fungal infections. However, its pharmacological effects are severely limited owing to its poor solubility and low bioavailability. In order to solve these problems, a sulfobutyl ether-ß-cyclodextrin compound was used to prepare an intramuscular injection to improve the bioavailability of posaconazole. The extracorporeal dissolution rate of posaconazole was markedly improved by this inclusion complex with >90% being released within 5 min, and the in vivo pharmacokinetics were studied using a HPLC/MS/MS method for quantifying posaconazole and the posaconazole-sulfobutyl ether-ß-cyclodextrin inclusion complex in rat blood. Posaconazole and an internal standard, itraconazole, were extracted by protein precipitation using acetonitrile. The concentration range of posaconazole was 0.05-4.0 µg/mL with good linearity (r = 0.9980), the peak concentrations of pure posaconazole and the inclusion complex were 0.565 ± 0.102 µg/mL and 1.12 ± 0.091 µg/mL, the values for AUC0-t were 12.2 ± 2.5 and 19.9 ± 2.5 µg h/mL, and the values for AUC0-∞ were 16.4 ± 3.2 and 25.0 ± 3.5 µg h/mL, respectively. The main pharmacokinetics parameters showed significant differences (P < 0.01). Compared with pure posaconazole, the posaconazole-sulfobutyl ether-ß-cyclodextrin inclusion complex markedly improved the bioavailability of posaconazole.

[Design and realization of X-ray TUBE HEAD control system in the CBCT system].

Cone beam computer tomography (CBCT) has advantages of high precision, low radiation and high image quality. It has been developing quickly since it was applied clinically. In order to control X-ray TUBE HEAD effectively in Dental CBCT, X-ray TUBE HEAD Control System was designed and realized in this study. This control system is the core of CBTC system, which includes the communication between CBCT system and computer, the control of X-ray tube head by CBCT system main control board and the synchronization between main control board and the flat panel detector. Control circuit of the control system and corresponding operating software were designed with PIC16F877A as the core. This control system has been put into use in current CBCT system successfully.

Modifying the structure and flow behaviour of aqueous montmorillonite suspensions with surfactant.

Colloidal suspensions of plate-like particles undergo a variety of phase transitions. The predicted isotropic/nematic transition is often pre-empted by a sol/gel transition, especially in suspensions of the most commonly used natural swelling clay montmorillonite (MMT). A number of factors, including charge interactions, flexibility and salt concentration, may contribute to this competition. In this study, the effect of surfactant adsorption on suspensions of MMT was studied using rheology, small-angle X-ray scattering, static light scattering and optical microscopy. The addition of a polyetheramine surfactant reduced the moduli of the system and shifted the sol/gel transition to a much higher clay concentration, compared with suspensions of bare clay particles. Yet, scattering data revealed no change in suspension structure on length scales up to around a micrometre. Primary aggregates remain at this length scale and no nematic phase is formed. There is, however, a change in structure at large length scales (of order 20 µm) where light scattering indicates the presence of string-like aggregates that disappear on addition of surfactant. Microscope images of dried suspensions also revealed a string-like structure. The dried strings show strong birefringence and may consist of concentric cylinders, self-assembled from clay sheets.

Microcapsules composed of cross-linked organoclay.

Polyelectrolyte-modified montmorillonite particles were used to stabilize oil-in-water Pickering emulsions, which were then bound together by an oil-soluble cross-linker to obtain microcapsules. It was determined how the morphology and rigidity of the microcapsules changed as polyelectrolyte and cross-linker concentrations were varied. Well-defined microcapsules could be formed by using a moderate concentration of polyelectrolyte, and the higher the cross-linker concentration, the more rigid the microcapsules. Dried microcapsules were observed using SEM, and it was shown that the clay platelets lie flat next to each other on the microcapsule surface, forming an armor-like structure.

Optimizing organoclay stabilized Pickering emulsions.

Oil-in-water emulsions were prepared using montmorillonite clay platelets, pre-treated with quaternary amine surfactants. In previous work, cetyl trimethylammonium bromide (CTAB) has been used. In this study, two more hydrophilic quaternary amine surfactants, Berol R648 and Ethoquad C/12, were used and formed Pickering emulsions, which were more stable than the emulsions prepared using CTAB coated clay. The droplets were also more mono-disperse. The most hydrophilic surfactant Berol R648 stabilizes the emulsions best. Salt also plays an important role in forming a stable emulsion. The droplet size decreases with surfactant concentration and relatively mono-disperse droplets can be obtained at moderate surfactant concentrations. The time evolution of the droplet size indicates a good stability to coalescence in the presence of Berol R648. Using polarizing microscopy, the clay platelets were found to be lying flat at the water oil interface. However, a significant fraction (about 90%) of clay stayed in the water phase and the clay particles at the water-oil interface formed stacks, each consisting of four clay platelets on average.

Adsorption of polyetheramines on montmorillonite at high pH.

Adsorption of a series of polyetheramines on montmorillonite in aqueous suspension was investigated by a range of methods: elemental analysis, atomic absorption spectroscopy, measurement of pH, conductivity and electrophoretic mobility, and small-angle X-ray scattering. Adsorption proceeds through an ion exchange mechanism. The maximum surface coverage attained is equivalent to about 40% of the cationic exchange capacity of the clay. Adsorption of the poly(oxypropylene) block adjacent to the amine group onto the clay surface may contribute to this. Surprisingly the adsorption takes place at pH conditions well above the pK(a) of the amine surfactants, where they are not protonated in the bulk solution. The surface coverage as a function of molar mass broadly agrees with predictions assuming adsorbed polymers adopt a densely packed mushroom configuration at the clay surface.