Microarray Patches: Poking a Hole in the Challenges Faced When Delivering Poorly Soluble Drugs

Poorly soluble drugs constitute more than 60% of currently marketed pharmaceuticals with over two-thirds of promising new chemical entities failing to enter a clinical setting due to solubility issues. Although oral formulations have made some impact, alternative enhancement strategies for administration of such molecules are actively sought. Over the last decade, innovation on a global scale has enabled the expansion of the frontiers of microarray patches (MAPs) further than ever before. Initially designed to load low doses of hydrophilic and potent therapeutic agents, MAPs are now becoming a viable strategy for the immediate and long-acting delivery of poorly soluble drugs through the skin. This together with the advantages of transdermal administration over the oral and parenteral routes, make of MAPs an appealing platform for the development of products with increased patient compliance. Undoubtedly, MAPs will soon become a readily available therapeutic alternative, and experts from academia, industry and regulatory bodies are working together aiming to facilitate the progression of MAPs toward safe and effective clinical use. This review aims to highlight the ability of MAPs to deliver poorly soluble actives, discuss the mechanisms behind in-skin drug absorption, and evaluate the future direction of the field.     

The cyclization index and toughness of gel spun polyacrylonitrile (PAN) proportionality with its heat of stabilization

The spun tapes of synthesized PAN, its copolymer with 1 wt% itaconic acid, and doped version with 1 wt% sodium dodecyl sulfate (SDS) all showed stripy, even, and compact cross-sections as the hallmark of gel forming products. PAN doping with SDS and acrylonitrile copolymerization with itaconic acid reduced its dimethylformamide (DMF) solution structural viscosity index (Δη) by 50% and 30%, respectively, at 675 s^??1. In addition, the modification of synthesized PAN through doping and acrylonitrile copolymerization with itaconic acid led to severe and mild gelation temperature decrease, respectively. The stabilization peak of the synthesized PAN tape was enhanced as much as 25 °C by 900% hot drawing, decreased by about 10 °C through copolymerization, while experienced small temperature changes through doping. The second derivative of Fourier transform infrared and Gaussian fitting was used to analyze the tapes cyclization due to stabilization treatment through introducing I_sd index. 10 min I_sd index was raised as much as 430% and 800% in comparison with the synthesized PAN through its doping or acrylonitrile copolymerization with itaconic acid, respectively. Further 180 min of I_sd index, however, showed the same proportional increase as toughness of the drawn tapes versus their heat of stabilization through their physical and chemical modifications.     

The rheological,mechanical and templating effects of graphene oxide nanosheets in filled gel spun polyacrylonitrile

Polyacrylonitrile (PAN) in dimethylformamide solution containing 0.25 or 1 wt% graphene oxide (GO) was gel spun to tapes. Scanning electron microscopy of tapes showed compact staircase cross-sections hallmarking the gel spun products. Low shear rate rheometry of the tape precursors revealed a viscosity increase, while the structural viscosity indexes of dispersions dropped to 40 and 70% at high shear rates by 0.25 and 1 wt% GO inclusion, respectively. Furthermore, the sol–gel transition temperature of PAN solution was enhanced by about 2.5 and 10 °C with 0.25 and 1 wt% GO inclusion, respectively. Strain sweep test implied a gel-to-sol transition from 9 to 28% by 1 wt% GO inclusion. The experimental reinforcement coefficient corresponded the aligned Halpin–Tsai model confirming the suitable dispersion preparation route namely master batch dilution implementing strong interphase formation among the PAN chains and GO platelets. Molecular evolution analysis during air stabilization through a combined second derivative of FTIR spectra, Gaussian peak fitting represented by I_sd index, indicated the initial cyclization at 290 °C followed by its enhanced rate. Final I_sd was noticed to be 48% higher for the tapes containing GO nanosheets. GO inclusion not only enhanced the tape heat of stabilizations but also differentiated its proportional I_sd and toughness dependency based on the heat of stabilization.     

Comparison of pristine and polyaniline‐grafted MWCNTs as conductive sensor elements for phase change materials: Thermal conductivity trend analysis

Phase change materials (PCMs) function based on latent heat stored on or released from a substance over a slim temperature range. Multiwalled carbon nanotubes (MWCNTs) and polyaniline are important elements in sensor devices. In this work, pristine and polyaniline‐grafted MWCNTs (PANI‐g‐MWCNTs) were applied as conductive carbon‐based fillers to make PCMs based on paraffin. The attachment of PANI to the surface of MWCNTs was proved by Fourier transform Infrared analysis. Dispersion of MWCNTs in paraffin was studied by wide‐angle X‐ray scattering. Heating and solidification of PCM nanocomposites were investigated by differential scanning calorimetry, while variation in nanostructure of PCMs during heating/solidification process was evaluated by rheological measurements. It was found that after 30 min of sonication, the samples filled with 1 wt % MWCNTs have melting and solidification temperatures of 29 and 42 °C, respectively. It was also found that PANI attachment to MWCNTs significantly changes thermal conductivity behavior of PCM nanocomposites. The developed MWCNTs‐based sensor elements responded sharply at low MWCNTs content, and experienced an almost steady trend in conductivity at higher contents, while PANI‐g‐MWCNTs sensor followed an inverse trend. This contradictory behavior brought insight for understanding the response of PCMs against thermal fluctuations. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45389.     

Interrelationship of thermal and mechanical properties of poly(ethylene terephthalate)/poly(ethylene 2,6‐naphthalate)/graphene nanocomposites

In the present work, attempts were made to investigate the thermal and mechanical properties of melt‐processed poly(ethylene terephthalate) (PET)/poly(ethylene 2,6‐naphthalate) (PEN) blends and its nanocomposites containing graphene by using differential scanning calorimetry and tensile test experimenting. The results showed that crystallinity, which depends on a blend ratio, completely disappeared in a composition of 50/50. By introducing graphene to PET, even in low concentrations, the crystallinity of samples increased, while the nanocomposite of PEN indicated reverse behavior, and the crystallinity was reduced by adding graphene. In the case of PET‐rich (75/25) nanocomposite blends, by increasing the nano content in the blend, the crystallinity of the samples was enhanced. This behavior was attributed to the nucleating effect of graphene particles in the samples. From the results of mechanical experiments, it was found in PET‐rich blends that by increasing the PEN/PET ratio, the modulus of samples decreased, whereas in the case of PEN‐rich blends, a slight increment of modulus is seen as a result of the increment of the PEN/PET ratio. The two contradicting behaviors were attributed to the reduction of crystallinity of PET‐rich blends by enhancement of PEN/PET ratio and the rigid structure of PEN chains in PEN‐rich blends. Unlike the different modulus change of PET‐rich and PEN‐rich blends, the nanocomposites of these blends similarly indicated an increment of modulus and characteristics of rigid materials by increasing the nano content. Furthermore, the same behavior was detected in nanocomposites of each polymer (PET and PEN nanocomposites). The alteration from ductile to rigid conduction was related to the impedance in the role of graphene plates against the flexibility of polymer chains and high values of graphene modulus. J. VINYL ADDIT. TECHNOL., 23:210–218, 2017. © 2015 Society of Plastics Engineers     

Behavior of Retrofitted URM Walls under Simulated Earthquake Loading

Unreinforced masonry (URM) buildings perform poorly under seismic forces and have been identified as the main cause of loss of life in recent earthquakes. Many of these structures fail in out-of-plane bending due to the lack of reinforcement. In this study, the experimental results from three half-scale unreinforced brick walls retrofitted with vertical composite strips are presented. The specimens were subjected to cyclic out-of-plane loading. Five reinforcement ratios and two different glass fabric composite densities were investigated. The mode of failure is controlled by tensile failure when wider and lighter composite fabrics are used and by delamination when stronger ones are used. The tested specimens were capable of supporting a lateral load up to 32 times the weight of the wall. A deflection as much as 2% of the wall height was measured. Although both URM walls and composite strips behave in a brittle manner, the combination resulted in a system capable of dissipating some energy. Retrofitting URM walls with composite strips proved to be a good and reliable strengthening alternative.     

Comparison of pH-dependent sonodisruption of re-assembled casein micelles by 35 and 130 kHz ultrasounds

Sonodisruption behavior of re-assembled casein micelles was compared at two ultrasound frequencies (35 and 130 kHz) by turbidity measurement and laser-diffraction based particle size analysis. Sonochemical ultrasound (130 kHz) was more effective than power ultrasound (35 kHz) in micelle disruption. This was attributed to the higher strain rates generated upon implosion of cavities, as well as the liberation of more free radicals to the surrounding medium. The higher the pH of solution, the more effective was the ultrasonic disruption due to a looser expanded assembly of particles at higher pH values. Sonochemical ultrasound decreased the consistency coefficient of casein solutions and increased their flow index except at a pH value of 6.35, while power ultrasound did not affect the flow behavior of solutions across the whole pH range.     

The quantitative risk assessment of a hydrogen generation unit

The safety of hydrogen generation process is a major concern. This paper discusses the quantitative analyzes of the risk imposed on neighborhood from the operation of a hydrogen generator using natural gas reforming process. For this purpose, after hazard identification, the frequency of scenarios was estimated using generic data. Quantitative risk assessment was applied for consequence modeling and risk estimation. The results revealed that, jet fire caused by a full bore rupture in Desulphurization reactor has the highest fatality (26person) and affects the largest area of 5102 m². The lethality radius, maximum radiation and safe distance of this incident were 140 m, 370 kW/m² and 225 m respectively. A full bore rupture in Reformer can lead to the most dangerous flash fire. In this incident the concentration of released material in LFL zone (area of 1483.17 m²) and ½ LEL zone (area of 1970.74 m²) were 61,125 ppm and 40,000 ppm respectively. QRA is a credible method to assess the risks of hydrogen generation process.     

Uncertainty evaluation of calculated and measured kinetics parameters of Tehran Research Reactor

Effective delayed neutron fraction β_eff and neutron generation time Λ are important factors in reactor physics calculation and transient analysis. In the first stage of this research, these kinetics parameters have been calculated for two states of Tehran Research Reactor (TRR), i.e. cold (fuel, clad and coolant temperature 20 °C) and hot (fuel, clad and coolant temperature 65, 49 and 44 °C, respectively) states using MTR_PC computer code. The ratio of (β_eff)_i/(β_eff)_core plays an important role in reactivity accident analysis codes. This parameter and its contribution to effective delayed neutron fraction from each nucleus have been calculated in cold and hot reactor states. Uncertainty of effective delayed neutron fraction is evaluated in terms of following four quantities; basic delayed neutron constants, delayed neutron spectra, energy dependence of delayed neutron yield (ν_d) and fission cross-section of ²³⁵U and ²³⁸U. In the second stage, these parameters have been measured with an experimental method based on Inhour equation. The calculated and measured values are in good agreement. Relative Percent Errors (RPEs) are 2.8% for β_eff and 5.7% for Λ in the cold state.     

Development of a 2-D 2-group neutron noise simulator for hexagonal geometries

In this paper, the development of a neutron noise simulator for hexagonal-structured reactor cores using both the forward and the adjoint methods is reported. The spatial discretisation of both 2-D 2-group static and dynamic equations is based on a developed box-scheme finite difference method for hexagonal mesh boxes. Using the power iteration method for the static calculations, the 2-group neutron flux and its adjoint with the corresponding eigenvalues are obtained by the developed static simulator. The results are then benchmarked against the well-known CITATION computer code. The dynamic calculations are performed in the frequency domain which leads to discarding of the time discretisation. Then, the developed 2-D 2-group neutron noise simulator calculates both the discretised forward and the adjoint reactor transfer function between a point source and its induced neutron noise, by assuming the neutron noise source as an “absorber of variable strength” type. The neutron noise induced by a “vibrating absorber” type of noise source may also be modeled using the calculated transfer function. The viability of the simulator is verified for different benchmark cases.