Vitamin a palmitate-loaded NLCs vs. SLN for cosmetic application with a study of their controlled release, skin permeation and characterization.

Nanostructured lipid carriers (NLC) are a new generation of Solid Lipid Nanoparticles (SLN), with improved drug loading capacity, stability, skin permeation, and sustained release of the encapsulated active. The encapsulation of vitamin A, a chemically labile cosmetic ingredient for anti-aging therapy, is ensued for effective delivery of the active. The method used for the production of the lipid nano-carriers is the hot homogenization technique. Furthermore, this study entailed a 23-factorial model design of experiment, where the three factors changed in the eight NLC formulation were surfactant to solid lipid ratio, Vitamin A Palmitate (RP), and prickly pear (PP) oil. The purpose of this study was to investigate the formulation and characterization of the NLCs, in an aim to find trends in changing the three factors constituting the matrix of the carrier on their exhibited characteristics, in order to arrive at an optimal formulation for the delivery of vitamin A to the skin in terms of particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), in-vitro release and ex-vivo skin permeation. The results attained from the parameters investigated were further analyzed using a statistical program, Design Expert. The particle size for the eight NLC carriers were in the range of 197.6 nm to 240.2 nm. The overall PDI for most of the formulations was lower than 0.3. The SLN had a much bigger particle size of 296.7 nm and PDI of 2.47. The release patterns in both in-vitro and ex-vivo showed differences in trends for the two types of carriers. The ZP of the formulations was not indicative of their predicted stability. Instead, the relative constitution of the solid to liquid lipid was pivotal in assessing the variation witnessed in both particle size and PDI upon storage for 6 weeks. The EE% showed a close dependence on the amount of PP oil in the matrix, where an equal or higher composition to the RP is required for effective incorporation. The thermal behavior assessed using Differential Scanning Calorimetry (DSC), of the 9 formulations showed a similar trend for 7 NLC, where minimal transitions suggesting amorphous characteristics were observed. The remainder NLC formulation exhibited similar transitions to that of the SLN, suggesting a higher order of crystallinity. The lower melting point of the NLCs in comparison to the pure solid lipid is an indication to the incorporation of the RP within the matrix. The total release of the in-vitro trials showed a close dependence on the amount of RP, where a higher composition of the latter lead to enhanced diffusion, and total release for the NLCs. The initial diffusion flux, however, was different and showed a close relation to the EE%. Formulations with high EE% showed a more sustained release, as opposed to more pronounced burst release exhibited by formulations with low EE%. The formulations that exhibited the highest in-vitro release were further assessed for skin permeation studies across a natural, rat skin membrane using Franz Diffusion Cell (FDC). The formulation with the higher surfactant ratio has shown higher permeation across the membrane, but lower skin retention. This was confirmed by slicing and extracting RP from various skin sections after the ex-vivo experiment. Imaging using Scanning Electron Microscopy (SEM) has also been performed on the SLN and NLC. Finally, changes in the constituting matrix of the nano-lipidic carrier gives wide variation in its properties, and hence allows it to be tinkered and adjusted for a particular use. Finally, the NLC formulations, in general, exhibited differences in their respective assessed parameters, all showing an improvement compared to the SLN. The optimal formula consisted of a higher composition of all lipidic constituents, namely Vitamin A and PP oil content, and a lower surfactant to solid lipid ratio. Its choice was based on stability and EE% as the most important parameters. The exhibited particle size and PDI of this formulation was 236.8 nm, and 0.24 upon formulation, and 265.3 nm and 0.27 after storage for 6 weeks, respectively. The EE% was 95.1  1.1%, ZP -32.87 0.25 mV and total in-vitro release was 43 7.3%

Infrared Thermography (IRT) of Conjugate Heat Transfer (CHT) Problem and Comparison with Multiphysics Model

This work presents a problem undergoing conjugate heat transfer (CHT). Conjugate heat transfer problems are common is domestic heating/cooling, industrial heat exchangers, cooling of electronics (e.g. PC fans). It is to be noted that in conjugate heat transfer problems, the convection part of the heat transfer is dominated. In the given study, a hypothetical case is built where a heat source (a burning candle) is placed under a thin aluminium sheet. The aluminium sheet is exposed to wind velocity using a fan (velocity of ~1.75 m/s). The aluminium sheet is coated with acrylic paint to increase the infrared emissivity of the surface. FLIR® T1030sc camera is used to visualise the developed infrared signature. Precautions are taken to ensure the correctness of results. The given problem is simulated using ANSYS® Multiphysics, where fluid mechanics equations; continuity, Navier-Stokes and energy are coupled with the heat equation. This Multiphysics problem is solved using a finite volume method. Mesh sensitivity analysis is performed to ensure the correctness of results. The results from infrared thermography and the Multiphysics model are compared and found to be in reasonable accuracy

The association of center volume with transplant outcomes in selected high-risk groups in kidney transplantation

BACKGROUND: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. METHODS: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000-2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m RESULTS: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m CONCLUSIONS: Recipients of high-risk KT with BMI ≥ 35 kg/

Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences

Doing many things at a time: lack of power decreases the ability to multitask

Three studies investigated the effects of power on the ability to pursue multiple, concomitant goals, also known as multitasking. It was predicted that powerless participants will show lower multitasking ability than control and powerful participants. Study 1 focused on self‐reported ability to multitask in a sample of executives and subordinate employees. Studies 2 and 3 investigated the ability to dual‐task and to switch between tasks, respectively, using dual‐task and task‐switching paradigms. Across the studies, powerless individuals were less able to effectively multitask compared with control and powerful participants, suggesting that the detrimental effects of lack of power extend beyond single‐task environments, shown in past research, into multitasking environments. Underlying mechanisms are discussed

In Vitro & In Vivo Characterization of Tableted Spray-Congealed Lipid Microparticles for Extended Release of Vildagliptin

Vildagliptin (VG), a drug used for treatment of type 2 diabetes, is soluble in water and currently marketed as an instantaneous release tablet that is administered twice daily. VG is not available as an extended release dosage form. The aim of this project therefore, was to design an extended release oral drug delivery for VG that can be administered once daily by producing solid lipid microparticles using the Spray Congealing technique (SC). The SC is an environmentally friendly microparticles (MP) preparation process that can be utilized to produce MP without using any solvent. Drug with or without Carbomer® was dispersed in the melted lipid carriers and atomized through the two fluid nozzle of the Buchi® spray congealer leading to form MP loaded with VG. The produced VG loaded MP were characterized for their morphological features, yield, content and thermal properties. VG/MP were then pressed into tablets and their in vitro and in vivo release studies were investigated. Determination of VG in samples was done using validated High Pressure Liquid Chromatography HPLC-UV and Liquid Chromatography Mass Detector LC/MS methods of analysis for in vitro and in vivo studies respectively. VG microparticles were spherical in shape with a yield of 76 %. The drug content in the microparticles was found to be 98.8 %. The in vitro dissolution studies showed that VG was released from the tableted particles in an extended-release fashion for up to 24 hours when compared to the immediate-release VG marketed tablets. Moreover, no changes in the release profile were observed upon the storage of the formula for 6 months at 4 oC. The in vivo pharmacokinetics studies using mixed breed dogs reported a Cmax, Tmax, T1/2 and mean residence time of 118ng/ml, 3.4 h, 5.27 h and 9.8 h respectively for the tested formulation prepared by SC with a significant difference when compared to those of the reference immediate-release marketed drug (147 ng/ml, 1 h, 2.16 h and 2.8 h respectively). The mean area under the curve (AUC) values for the test and the reference were not significantly different as indication of comparable bioavailability. The IVIVC studies resulted in level A correlation with a correlation coefficient of 0.965. On the other hand, the multiple level C correlation showed a linear correlation for different pharmacokinetic parameters with the dissolution parameters. In conclusion, SC technology was successfully utilized for designing a once daily extended release drug delivery system of VG

Redesign of cylindrical shells by large admissible perturbations.

This dissertation has two primary objectives. First, to develop a LargE Admissible Perturbations (LEAP) methodology to redesign cylindrical shells for multiple modal requirements. Second, to develop the required (LEAP) algorithm to solve the resulting highly nonlinear problem and implement them in code RESTRUCT (REdesign of STRUCTures). The Perturbations Approach to Redesign (PAR) is used to formulate the redesign problem. Nonlinear perturbation equations of cylindrical shells for modal dynamics and static requirements are presented to support the theoretical development and the algorithm. Extensive numerical applications of cylindrical shell redesign for modal requirements are presented to confirm the theory and test the algorithm. The developed design methodology is very efficient in solving shell redesign problems without trial and error or repeated finite element analyses. Most important it proves that several redesign problems have no solutions. Analytical expressions of natural frequencies and energy distribution of segmented cylindrical shells are derived, using an energy Rayleigh-Ritz approach to prove the conclusions of the redesign methodology. The analytical derivation along with the redesign process by LEAP clarifies the potential and limitations of the redesign of cylindrical shells. Redesign related subjects such as null cognate space, modal coupling, modal distributions, mode crossing, equivalent or redundant frequency constraints, and stationary modes are introduced and discussed. The LEAP methodology developed in this dissertation for the redesign of cylindrical shells solves the redesign problem and identifies the unique modal characteristics of cylindrical shells, and further establishes the capability of the large admissible perturbations theory to solve two-state problems in structural analysis and design.Ph.D.Civil EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104907/1/9624563.pdfDescription of 9624563.pdf : Restricted to UM users only

Analysis of pressure wave dynamics in fuel rail system

A model of an amplified common rail fuel system is simulated in Matlab toanalyze the wave mechanics in the rail. The injectors are modeled as asystem of linear and non-linear ODE’s consisting of masses, a helical spring,compressibility effects from fluid volumes, and hydraulic flow throughorifices. The injector simulation then predicts the rate of oil consumption,which is then input into the rail model.The rail is modeled in three sections which are coupled together. The pointswhere the coupling occurs are the locations where the current firinginjector and the pump supply are connected to the rail. This allows themodel to control the pressure and velocity (as boundary conditions) atthese points. The rail model is based on the 1D, undamped wave equation,in a non-dimensional form [1] (in the position variable, x.) The Reduction ofOrder method was used to solve the wave equation with the Matlabfunction PDEPE.The model was run with two different sets of initial conditions - nominal(constant pressure and zero velocity,) and worst case using a simplifiedrepresentation of the pressure and velocity distribution at start of injection.This was done to determine the effect of rail waves at the start of injection,on the output of the model. The variation in fuel delivery, due to the variationin rail pressure, was then evaluated at three operating conditions - Idle,Peak Torque (PT) and High Speed Light Load (HSLL.) The simulation outputis then compared to analytical solutions of two forms of simplifiedgeometry, using the product method to solve the system [1.

Rough Surface Contact

This paper studies the contact of general rough curved surfaces having nearly identical geometries, assuming the contact at each differential area obeys the model proposed by Greenwood and Williamson. In order to account for the most general gross geometry, principles of differential geometry of surface are applied. This method while requires more rigorous mathematical manipulations, the fact that it preserves the original surface geometries thus makes the modeling procedure much more intuitive. For subsequent use, differential geometry of axis-symmetric surface is considered instead of general surface (although this “general case” can be done as well) in Chapter 3.1. The final formulas for contact area, load, and frictional torque are derived in Chapter 3.2