In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems

Objective: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach.

Significance: In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine.

Methods: SV-loaded SMEDDS were formulated using various proportions of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (polysorbate 80) and subjected to characterization, and physiologically-based pharmacokinetic (PBPK) modeling.

Results: According to the in vitro results, the selected SMEDDS consisted of 10.0% PEG 300 oleic glycerides, 67.5% PEG 400 caprylic/capric glycerides, and 22.5% polysorbate 80. The use of acid-resistant capsules filled with SV-loaded SMEDDS was found helpful in protecting the drug against early degradation in proximal parts of the GI tract, however, in silico simulations indicated that pH-controlled drug release system that dissolve in the distal parts of the intestine might further improve SV bioavailability (up to 7.20%).

Conclusion: The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release. The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms.     

Tough thermosetting polyurethanes and adhesives from rubber seed oil by hydroformylation

Rubber seed oil (RSO), extracted from the seeds of rubber trees, is inedible oil with high free fatty acid content. In order to add value to RSO, we prepared a polyol with primary OH groups via hydroformylation/hydrogenation. Free hydroxy fatty acids formed in the process were utilized as reactive diluents, viscosity reducers, and adhesion promoters through hydrogen bonding with the substrate. The structures of the oil and polyol were analyzed using a range of analytical methods. The polyol had a hydroxyl number of 244 mg KOH g⁻¹ and an acid number of 21 mg KOH g⁻¹. The polyurethane prepared from this polyol and diphenylmethane diisocyanate was a highly crosslinked, tough material with a glass transition at 44 °C, high tensile strength and elongation, and attractive electrical properties. When used as a wood adhesive, it displayed extraordinary shear strength characterized by substrate wood failure rather than cohesive failure of the polymer. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48509.     

Identification of buckwheat (Fagopyrum esculentum Moench) aroma compounds with GC–MS

Buckwheat has a strong characteristic aroma, but its phytochemical background has not yet been fully elucidated. The aims of this study were identification and quantification of individual compounds responsible for the buckwheat aroma. Volatiles from a freshly ground buckwheat flour were extracted by different methods: direct extraction with petroleum ether, pentane or methanol, distillation with Clevenger apparatus and a headspace solid-phase microextraction method. The extracts were analysed by GC–MS with electron ionisation. Compounds were identified by MS and by comparison of retention times with reference compounds. Direct extraction with methanol and distillation proved to be very efficient. In these extracts twenty-five and thirty-five compounds were identified, respectively. The first extract contained more hydrophilic compounds and the latter more volatile compounds. Most of the compounds were quantified and their odour activity value (OAV) calculated. Only two compounds (salicylaldehyde and phenylacetaldehyde) were found in both extracts. The compounds with the highest contribution to the buckwheat aroma were: 2,5-dimethyl-4-hydroxy-3(2H)-furanone, (E,E)-2,4-decadienal, phenylacetaldehyde, 2-methoxy-4-vinylphenol, (E)-2-nonenal, decanal, hexanal and salicylaldehyde (2-hydroxybenzaldehyde).     

Synthesis and antioxidant properties of fullero-steroidal covalent conjugates

Four new fullero-steroids were synthesized starting from γ-aminobutyric acid (GABA)-incorporated fulleropyrrolidine and corresponding sterols. The synthesis, characterization, preliminary study on in vitro antioxidant activity as well as the steady state photophysical properties are presented. All synthesized compounds showed antioxidant activity 2-3-fold higher than the parent fullerene. The most active compound appeared to be as potent as standard antioxidant BHT (2,6-di-tert-butyl-4-methylphenol). Also, all of them fluoresce 6-8-fold stronger than C₆₀, thus representing potential irradiation assisted pro-oxidants. With significantly increased lipophilicity, it could be expected that attached steroidal subunit enables better penetration of C₆₀ to living cell membranes, thus facilitating its antioxidant activity. Based on all obtained results, newly synthesized covalent fullero-steroidal conjugates represent good candidates for potential antioxidants as well as pro-oxidants.     

Applying the Brazil-nut approach to manufacture W-Cu-graded materials

W-Cu graded packings were produced under gravity and vertical vibration, from a granular medium (GM) formed by tungsten and copper agglomerates with agglomerate size distributions, which do not overlap. These bimodal packings were processed by powder metallurgy techniques to manufacture W-Cu graded pseudo-alloys with a variety of textures of the order of one millimeter. We present and discuss the temporal evolution of the W-Cu GM bed through photographs of two case- studies with frequencies of 600 and 900 Hz. Pre-sintered W-Cu-graded materials corresponding to vibration treatments of different duration are characterised by a SEM, and the tungsten concentration profiles are estimated by area analysis. Using a LASER dilatometer, we measured the temporal registers for the height of the GM bed for a wide range of frequencies and accelerations. Depending on the excitation level of the vibrated GM bed, three types of segregation regime were identified, as follows: segregation due to convection rolls, geometrical segregation aided by surface convection, and geometrical segregation. Only at low enough excitation, through geometrical segregation, does the GM bed reach a graded packing. This occurs due to the diffusive nature of this process, where the smaller agglomerates change their configurations through hopping in a potential energy gradient.We want to thank for the financial support by the Alexander von Humboldt Foundation and by the Deutsche Forschungsgemeinschaft within the program gradient materials under the project Mu 959/5. JF is very grateful to Prof. Manuel Cáceres and Prof. Shu San Hsiau and for stimulating discussions.     

Performance comparison of modified poly(vinyl alcohol) based membranes in alkaline fuel cells

There are several problems which are holding back the use of fuel cells. The utilization of fuel cells depends on the start-up costs which are very high due to the use of expensive materials for their construction. In that respect, we describe a cost-effective alkaline fuel cell (AFC) that uses solid, polymer based, membrane instead of conventionaly used, highly concentrated, corrosive, liquid alkaline electrolyte. This approach to AFC is potentially the basis of a simple, low-cost system, that can solve one of the problems of the highly-efficient and environment-friendly AFC.The focus of this paper are low cost composite alkaline membranes, based on poly(vinyl alcohol) (PVA). The PVA matrix is made by solution cast method and gamma irradiation crosslinking. Three different types of membranes are obtained in this manner - plain PVA membrane, PVA membrane cross-linked using gamma irradiation (γ-PVA) and composite PVA membrane doped with Mo (PVA-Mo). These membranes are immersed in the alkaline solution and investigated as anion exchange membranes. The performance of the solid alkaline fuel cells (SAFCs) containing these PVA membranes has been studied under hydrogen and oxygen gas flow on the Pt/C catalyst. Both, γ-PVA and PVA-Mo membranes are modified to absorb larger amounts of alkaline solution than the PVA membrane, thus greatly improving the performance of the SAFC, in terms of output power. This is clearly indicated in the polarisation curves. The electrochemical impedance spectroscopy measurements during the SAFC operation were also performed to give better insight in the effect observed. Investigation presented in this paper clearly indicates that solid alkaline PVA membranes can be used for the construction of the SAFCs.     

Rheology and bread‐making performance of gluten‐free formulations affected by different levels of sugar beet fibre,hydroxypropylmethylcellulose and water

This study investigated the application of hydroxypropylmethylcellulose (HPMC) (2%, 3%, 4%), sugar beet fibre (SBF) (3%, 5%, 7%) and water (210%, 220%, 230%) into maize‐based gluten‐free (GF) formulations and their effects on the GF batter rheology and bread quality. HPMC incorporation in higher amounts reduced the compliance values of GF batter samples and increased the values of dynamic moduli indicating an improvement in the GF batter elastic characteristic. The same course of action with a less pronounced influence on mentioned rheological parameters had SBF addition. GF bread quality evaluation in terms of specific loaf volume and crumb texture (hardness, cohesiveness and springiness) reveals that HPMC and SBF incorporation at higher levels enhanced these quality parameters. The inclusion of HPMC and SBF coupled with adequate water content can improve the nutritional value of GF bread without negative influence on bread quality.     

Morphogenesis and developmental ultrastructure of Nicotiana tabacum short glandular trichomes

The anatomy and ultrastructure of the short glandular trichomes occurring on young expanding leaves of Nicotiana tabacum were investigated using light and transmission electron microscopy. The objective of the present research was to characterize the cellular changes that occur during morphogenesis of short glandular trichomes, from initiation to senescence. Ultrastructural analysis of their secretory cells revealed characteristics common to gland cells: numerous mitochondria in highly organized cytoplasm, large nuclei, and an elaborate network of endoplasmic reticulum. Initial changes in nuclear and plastidial organization were observed at a more advanced secretory stage, marking the onset of senescence. During trichome senescence, gradual reduction of the cytoplasm density occurred along with structural changes of the plastids and the tonoplast. As a result of inward blebbing of the cytoplasm into the vacuole, membrane bound vesicular structures appeared in the vacuolar space. At the late secretory stage, marked by an increase in vacuolation and extraplasmic space, degenerative changes included further fragmentation of the cytoplasm and deterioration of the tonoplast. Multimembrane myelin bodies observed in the vacuolar space were indicative of membrane digestion although plasma membrane did not appear massively degraded.     

Synthesis,morphology, microstructure and magnetic properties of hematite submicron particles

We report on hydrothermal synthesis, plate-like morphology, microstructure and magnetic properties of hematite (α-Fe₂O₃) plate-like particles. The sample is obtained immediately after the hydrothermal process without using any template and without further heat treatment. The so-obtained sample is characterized by X-ray powder diffraction (XRPD), energy-dispersive X-ray spectroscopy (EDX), field-emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and superconducting quantum interference device (SQUID) magnetometer. XRPD confirms the formation of a single-phase hematite sample whereas EDX reveals that iron and oxygen are the only components of the sample. SEM, FE-SEM, TEM and HRTEM show that the sample is composed of plate-like particles. The width of the particles is ～500 nm whereas thickness is ～100 nm (aspect ratio 5:1). The HRTEM images exhibit well defined lattice fringes of α-Fe₂O₃ particles that confirm their high crystallinity. Moreover, the HRTEM analysis indicates the plate-like particles preferring crystal growth along [0 1 2] direction. Magnetic measurements display significant hysteretic behavior at room temperature with coercivity H_C = 1140 Oe, remanent magnetization M_r = 0.125 emu/g and saturation magnetization M_S = 2.15 emu/g as well as the Morin transition at T_M ～ 250 K. The magnetic properties are discussed with respect to morphology and microstructure of the particles. The results and comparison with urchin-like, rods, spherical, hexagonal, star-like, dendrites, platelets, irregular, nanoplatelets, nanocolumns and nanospheres hematites reveal that the plate-like particles possess good magnetic properties. One may conjecture that the shape anisotropy plays an important role in the magnetic properties of the sample.