Evaluating the Bioavailability of Carbamazepine Using a Novel SNEDDS Formulation

Central to the mechanism of how drugs work are the concepts of solubility and bioavailability. Drugs enter the body via absorption into the bloodstream, arrive at the target location, and bind to receptors to cause an effect. Drugs need to be soluble enough to pass through the cell membrane to enter and exit the bloodstream. Higher solubility generally correlates to higher bioavailability. Additionally, the smaller the particle size, the easier the drug will pass through the membrane into the blood plasma. Researchers have designed a system to categorize solubility class: Class I being high permeability and high solubility, Class II high permeability and low solubility, Class III low permeability and high solubility, and Class IV low permeability and low solubility. The study will use a Class II anticonvulsant, carbamazepine (CBZ). CBZ is a suitable candidate for this study because it requires a higher bioavailability due to its need to cross the blood brain barrier and act on the trigeminal nucleus. To increase bioavailability researchers have tried crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification. These methods have been successful at increasing bioavailability, but this experiment will focus on reducing particle size into a new self-emulsifying formulation. In particular, the formulation of CBZ in this study is a self nano-emulsifying drug delivery system (SNEDDS), which shows more promise than previous methods to increase bioavailability. This study will create a SNEDDS formulation as a nasal nebulizer mist delivery and compare it to a FDA approved oral suspension using a crossover rat model design. Sixteen Sprague-Dawley rats will be ordered through Central State University and normalized to the study environment for a minimum of one week. Pending IACUC approval from Central State University, the tail vein method will be used to collect blood samples. The samples will be stored until needed for analysis using ELISA, enzyme-linked immunosorbent assay, which will be used to determine the concentration of CBZ in blood plasma

Evaluating the Bioavailability of Carbamazepine Using a Novel SNEDDS Formulation

Carbamazepine (CBZ) is an anticonvulsant drug primarily used to treat epilepsy, bipolar disorder, trigeminal and glossopharyngeal neuralgia. CBZ is a lipophilic, poorly soluble drug that belongs to the class-2 category according to the Biopharmaceutics Classification System. As a class-2 drug, the plasma concentration of CBZ is limited by its ability to diffuse across biological membranes. To increase its bioavailability, different methods such as crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification were explored. Of these methods, Self Nano Emulsifying Drug Delivery Systems (SNEDDS) have shown to reduce particle size of CBZ molecules and improve its solubility. However, the bioavailability of CBZ administered as SNEDDS are not yet investigated. Given this background, the current study proposes to evaluate the bioavailability of these novel drug delivery systems using a rat model. The study is designed as a randomized controlled crossover experiment using 10-12 Sprague-Dawley rats divided equally into two groups. For this study, blood samples will be collected at 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes after administering two different formulations of CBZ nanoemulsions and stored at -20°C until ready for analysis. Plasma concentrations of CBZ will be determined by HPLC method. An unpaired t-test will be used to compare the significance between the two sets of data

Measurement of the D 0 → K - Π + Branching Fraction a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72296/1/j.1749-6632.1988.tb51529.x.pd

Search for Long-lived Charged Massive Particles in anti-p p Collisions at s**1/2 = 1.8 TeV

We report a search for production of long-lived charged massive particles in a data sample of 90 pb^{-1} of \sqrt{s} = 1.8 TeV p anti-p collisions recorded by the Collider Detector at Fermilab (CDF). The search uses the muon-like penetration and anomalously high ionization energy loss signature expected for such a particle to discriminate it from backgrounds. The data is found to agree with background expectations, and cross section limits of \cal{O} (1) pb are derived using two reference models, a stable quark and a stable scalar lepton.Comment: 14 pages, 3 figure

How does the tobacco industry attempt to influence marketing regulations? A systematic review

BACKGROUND: The Framework Convention on Tobacco Control makes a number of recommendations aimed at restricting the marketing of tobacco products. Tobacco industry political activity has been identified as an obstacle to Parties' development and implementation of these provisions. This study systematically reviews the existing literature on tobacco industry efforts to influence marketing regulations and develops taxonomies of 1) industry strategies and tactics and 2) industry frames and arguments. METHODS: Searches were conducted between April-July 2011, and updated in March 2013. Articles were included if they made reference to tobacco industry efforts to influence marketing regulations; supported claims with verifiable evidence; were written in English; and concerned the period 1990-2013. 48 articles met the review criteria. Narrative synthesis was used to combine the evidence. RESULTS: 56% of articles focused on activity in North America, Europe or Australasia, the rest focusing on Asia (17%), South America, Africa or transnational activity. Six main political strategies and four main frames were identified. The tobacco industry frequently claims that the proposed policy will have negative unintended consequences, that there are legal barriers to regulation, and that the regulation is unnecessary because, for example, industry does not market to youth or adheres to a voluntary code. The industry primarily conveys these arguments through direct and indirect lobbying, the promotion of voluntary codes and alternative policies, and the formation of alliances with other industrial sectors. The majority of tactics and arguments were used in multiple jurisdictions. CONCLUSIONS: Tobacco industry political activity is far more diverse than suggested by existing taxonomies of corporate political activity. Tactics and arguments are repeated across jurisdictions, suggesting that the taxonomies of industry tactics and arguments developed in this paper are generalisable to multiple jurisdictions and can be used to predict industry activity

Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017

BackgroundThe global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years.MethodsWe used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury.ResultsGlobally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change.ConclusionsWhile road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented

Charged particle multiplicity distributions in e + e − annihilation at 29 GeV: a comparison with hadronic data

The charged particle multiplicity distributions for two-jet events in e + e − annihilation at 29 GeV have been measured using the High Resolution Spectrometer at PEP. A Poisson distribution describes the data for both the complete event and for the single jets. In addition, no correlation is observed between the multiplicities in the two jets of an event. For fixed values of the prong number of the complete event, the multiplicity sharing between the two jets is in good agreement with a binomial distribution. The rapidity gap distribution is exponential with a slope equal to the mean rapidity density. These observations, which are consistent with a picture of independent emission of single particles, are contrasted to the results from soft hadronic collisions and conclusions are drawn about the nature of clusters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47881/1/10052_2005_Article_BF01570767.pd

Measurement of the Inclusive Jet Cross Section in pˉp{\bar p p} collisions at s=1.8\sqrt{s}=1.8 TeV

We present results from the measurement of the inclusive jet cross section for jet transverse energies from 40 to 465 GeV in the pseudo-rapidity range $0.1<|\eta|<0.7$. The results are based on 87 $pb^{-1}$ of data collected by the CDF collaboration at the Fermilab Tevatron Collider. The data are consistent with previously published results. The data are also consistent with QCD predictions given the flexibility allowed from current knowledge of the proton parton distributions. We develop a new procedure for ranking the agreement of the parton distributions with data and find that the data are best described by QCD predictions using the parton distribution functions which have a large gluon contribution at high $E_T$ (CTEQ4HJ).Comment: 123 pages, 46 figure

Experimental limits on monojet production in e+e- annihilation at 29 GeV

A search was made for e+e---&gt;X1X2 where X1 consists of one or more light unobservable particles and X2 decays promptly to a visible jet of particles. One event was found for an integrated luminosity of 176 pb-1, a rate consistent with known backgrounds. This result places a significant constraint on a number of theoretical models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25641/3/0000191.pd