Rheological investigation of poly(vinyl alcohol)/poly(N-vinyl pyrrolidone) mixtures in aqueous solution and hydrogel state

Rheological behavior of poly(vinyl alcohol) (PVA) and poly(N-vinyl pyrrolidone) (PVP) mixtures in aqueous solutions and hydrogel state was investigated. The complex dependence of the viscosity on PVA/PVP mixture composition could be attributed to cumulative effects of electrostatic interactions, hydrogen bonding or association phenomena. Physical hydrogels were prepared by freezing/thawing method and their viscoelastic properties were followed as a function of number of cryogenic cycles and aging time at 37 °C. From swelling experiments, it was observed that the diffusion of water molecules into the hydrogel pores is Fickian (for low number of cryogenic cycles) and it becomes pseudo-Fickian as the sample is submitted to more than 10 freezing/thawing cycles. PVA/PVP hydrogels obtained by physical interactions present a high degree of tailorability and they are suitable candidates for biomedical applications.     

CRKL,AIFM3, AIF,BCL2, and UBASH3A during Human Kidney Development

We aimed to investigate the spatio-temporal expression of possible CAKUT candidate genes CRKL, AIFM3, and UBASH3A, as well as AIF and BCL2 during human kidney development. Human fetal kidney tissue was stained with antibodies and analyzed by fluorescence microscopy and RT-PCR. Quantification of positive cells was assessed by calculation of area percentage and counting cells in nephron structures. Results showed statistically significant differences in the temporal expression patterns of the examined markers, depending on the investigated developmental stage. Limited but strong expression of CRKL was seen in developing kidneys, with increasing expression up to the period where the majority of nephrons are formed. Results also lead us to conclude that AIFM3 and AIF are important for promoting cell survival, but only AIFM3 is considered a CAKUT candidate gene due to the lack of AIF in nephron developmental structures. Our findings imply great importance of AIFM3 in energy production in nephrogenesis and tubular maturation. UBASH3A raw scores showed greater immunoreactivity in developing structures than mature ones which would point to a meaningful role in nephrogenesis. The fact that mRNA and proteins of CRKL, UBASH3A, and AIFM3 were detected in all phases of kidney development implies their role as renal development control genes.     

Thermal stability of poly(methyl methacrylate-co-butyl acrylate) and poly(styrene-co-butyl acrylate) polymers

Thermal stability of poly(methyl methacrylate-co-butyl acrylate) and poly(styrene-co-butyl acrylate) modified with a small amount of acrylic acid and/or N-methylolacrylamide as a crosslinking agent was studied in this work. Programmed thermogravimetric analysis has been used to study the effect of copolymer composition on thermal stability, over a temperature range from 50 to 450°C, under a constant flow of nitrogen. Kinetic parameters of thermal degradation, activation energy, pre-exponential factor, and reaction order were obtained by using MacCallum-Tanner's approach. Kinetic data indicate that the thermal degradation of the investigated copolymer systems is the first order reaction, and that the increase of activation energy may be an indication of thermal stability changes in copolymer systems.     

QbD for pediatric oral lyophilisates development: risk assessment followed by screening and optimization

Objective: This study proposed the development of oral lyophilisates with respect to pediatric medicine development guidelines, by applying risk management strategies and DoE as an integrated QbD approach.

Methods: Product critical quality attributes were overviewed by generating Ishikawa diagrams for risk assessment purposes, considering process, formulation and methodology related parameters. Failure Mode Effect Analysis was applied to highlight critical formulation and process parameters with an increased probability of occurrence and with a high impact on the product performance. To investigate the effect of qualitative and quantitative formulation variables D-optimal designs were used for screening and optimization purposes.

Results: Process parameters related to suspension preparation and lyophilization were classified as significant factors, and were controlled by implementing risk mitigation strategies. Both quantitative and qualitative formulation variables introduced in the experimental design influenced the product’s disintegration time, mechanical resistance and dissolution properties selected as CQAs. The optimum formulation selected through Design Space presented ultra-fast disintegration time (5?seconds), a good dissolution rate (above 90%) combined with a high mechanical resistance (above 600?g load).

Conclusions: Combining FMEA and DoE allowed the science based development of a product with respect to the defined quality target profile by providing better insights on the relevant parameters throughout development process. The utility of risk management tools in pharmaceutical development was demonstrated.     

Can Mean‐Curvature Flow be Modified to be Non‐singular?

This work considers the question of whether mean‐curvature flow can be modified to avoid the formation of singularities. We analyze the finite‐elements discretization and demonstrate why the original flow can result in numerical instability due to division by zero. We propose a variation on the flow that removes the numerical instability in the discretization and show that this modification results in a simpler expression for both the discretized and continuous formulations. We discuss the properties of the modified flow and present empirical evidence that not only does it define a stable surface evolution for genus‐zero surfaces, but that the evolution converges to a conformal parameterization of the surface onto the sphere.     

Connecting Polygonizations via Stretches and Twangs

We show that the space of polygonizations of a fixed planar point set S of n points is connected by O(n ²) “moves” between simple polygons. Each move is composed of a sequence of atomic moves called “stretches” and “twangs,” which walk between weakly simple “polygonal wraps” of S. These moves show promise to serve as a basis for generating random polygons.     

Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour).     

Influence of trehalose addition on antioxidant activity,colour and texture of orange jelly during storage

The aim of this study was to investigate influence of partial replacement of sucrose with trehalose on phenolics, antioxidant activity, colour and texture of orange jelly during 135 days of storage under the light at room temperature. After preparation, phenol content was 1185.6 and 1050.3 mg GAE kg^?1 in orange jelly and orange jelly with trehalose addition, respectively. Loss of phenols during 135 days of storage in orange jelly was 27.8% in comparison with 9.14% in orange jelly with trehalose addition. Browning index of samples with trehalose addition had lower values than orange jelly after their preparation as well as after storage. Evaluated textural parameters were gel strength, rapture strength, brittleness and adhesiveness. After preparation, both jellies had the same gel strength and adhesiveness. Orange jelly had higher rapture strength and higher value of brittleness than orange jelly with trehalose addition.