Pharmacy and Pharmaceutical Sciences Commons^™

Ehtnobotanical- And Chemometric-Guided Investigation Of Phytolacca Americana L., Michael Chan

Electronic Theses and Dissertations

No abstract provided.

Endangered Plant Species For Potential Drug Leads And Anticancer Prototypes For Treatment Of Breast And Pancreatic Cancers, Joonseok Oh

Electronic Theses and Dissertations

No abstract provided.

Influence Of Hot Melt Extrusion Processing Parameters On The Properties Of A Pharmaceutical Formulation, Saad M. Alshahrani

Electronic Theses and Dissertations

Hot melt extrusion (HME) is an old technology that has been recently adapted to be used in the pharmaceutical industry. HME is a continuous process that is widely used to produce a solid dispersion matrix. The aim of this dissertation is to evaluate different factors that will affect the pharmaceutical formulation properties that are produced using HME. For HME, there are different variables that will affect the product quality such as processing parameters, material selection, material ratio, and the presence of gas or moisture. One aim of this study is to find the most significant factor that affects the product …

Non-Invasive Drug Delivery To The Posterior Segment Of The Eye: Development Of Formulation Strategies And Evaluation Of Ocular Distribution And Pharmacological Activity, Goutham Reddy Adelli

Electronic Theses and Dissertations

Diseases of the posterior segment of the eye such as diabetic retinopathy, age related macular degeneration and glaucoma are the leading causes for blindness throughout the world. Topical eye drops is the most convenient formulation for daily application. The human eye, however, presents major physiological and dynamic barriers for the topically administered drug/molecule from reaching the retina. Similarly, the blood-retinal and blood-aqueous barriers restricts passage of drug from systemic circulation into the eye. Although intravitreal injections are the gold standards for the treatment of posterior segment ocular diseases, they are associated with pain, inflammation, endopthalmitis and infection. So there is …

Evaluation Of Novel Ligands For Opioid Receptors, Amer Hussien Tarawneh

Electronic Theses and Dissertations

No abstract provided.

Design, Synthesis And Cannabinoid Receptor Activity Of Benzofuran Ligands, Eric William Bow

Electronic Theses and Dissertations

The endocannabinoid system is a complex homeostatic signaling system controlled through the actions of two g-protein coupled receptors, cannabinoid receptor 1 (cb1) and cannabinoid receptor 2 (cb2). Significant neuronal expression and distribution of cb1 throughout the brain establishes its function as a major synaptic signaling receptor, and in regards to the actions of cannabis sativa, it is the primary mediator of the psychotropic effects of marijuana. Conversely, cb2 expression is confined to microglial cells in the brain and predominantly peripheral immune cells. The expression of cb2 provides a pharmacological basis for the well-documented immunomodulatory effects of cannabis, providing a potential …

Development Of The Medication Non-Adherence Scale (Mnas) And The Medication Non-Persistence Scale (Mnps), Amod Sudhir Athavale

Electronic Theses and Dissertations

No abstract provided.

Novel Delivery Systems For Iron Replenishment, Naresh Modepalli

Electronic Theses and Dissertations

Iron is an integral part of hemoglobin and essential for the production of red blood cells. Iron deficiency and the resulting anemia are major nutritional deficiency disorders. The majority of patient populations suffering from iron deficiency anemia (IDA) are women of child bearing age and children of all ages. Iron deficiency is a complication of various other chronic conditions. Oral iron salts or colloidal parenteral iron formulations are treatment options for iron replenishment since several decades, but they are associated with severe side effects along with other patient noncompliance issues. Transdermal delivery of iron could be a potential alternative to …

Transdermal Iontophoretic Delivery Of Lipophilic Drugs, Abhishek Juluri

Electronic Theses and Dissertations

Iontophoresis is one of the most widely studied active technique for enhancing transdermal delivery of drugs. However, its ability to enhance the delivery of highly lipophilic compounds is poor due to lack of any charge and poor water solubility of molecules. Propofol, a sedative and anesthetic drug was chosen as a one of the model lipophilic drug in this study. Initially, feasibility of delivery of propofol phosphate, a water soluble prodrug of propofol, via transdermal route using iontophoresis in combination with chemical permeation enhancers was investigated. Cathodal iontophoresis in combination with 0.1% sodium dodecyl sulphate synergistically enhanced the flux of …

Lipid & Surfactant Based Systems For Improved Delivery Of Poorly Soluble Apis, Sri Satyasai Nagendra Babu Punyamurthula

Electronic Theses and Dissertations

A large number of pharmaceutical compounds belong to class II and IV of biopharmaceutical classification of drug (BCS). Class II compounds are limited by their poor aqueous solubility, while class IV compounds suffer from poor solubility and permeability. This translates to poor absorption and low plasma levels post oral administration. Lipids comprise of fatty acids and their derivatives and are considered a biocompatible option for drug delivery. In the studies discussed in following chapters, lipid based drug delivery systems (LBDDS) have been utilized in improving the handling, ease of formulation, solubility and bioavailability of three compounds. In the first study, …

Protein-Ligand Interaction Studies And Identification Of New Drug-Like Hits As Cannabinoid Receptor Modulators, Pankaj Pandey

Electronic Theses and Dissertations

The cannabinoid receptors (CB1 and CB2) belong to the family of class A GPCRs. The CB1 receptor is predominately found in the central nervous system and regulates various neuromodulatory and physiological processes while CB2 receptors are found in peripheral tissues, particularly in the immune system tissues. This dissertation reports several projects including: (1) an examination of the putative binding modes of Cannabis-derived ligands with CB1 and CB2 receptors, (2) the identification of novel CB1 inverse agonists, and (3) the identification of allosteric site(s) in the CB2 receptor and screening of new CB2 allosteric modulators (AMs).

Chapter 1 describes background information …

Versatility Of Hot-Melt Extrusion For Dosage Form Design, Sultan Mohammad Alshehri

Electronic Theses and Dissertations

Recently, Hot Melt Extrusion (HME) has attracted the attention of pharmaceutical companies and scientists as a technique for manufacturing a variety of dosage forms. In this research, HME was applied in different ways to achieve different goals, such as solubility enhancement, taste masking, solid state stability enhancement, and sustained release formulations for oral drug delivery, using one model drug, mefenamic acid. For solubility enhancement and taste masking formulations, Eudragit EPO was blended with MA in different ratios (20, 25, 30, and 40% of drug loads) and processed by a hot melt extruder to produce a solid dispersion system. FT-IR analysis …

Influence Of Novel Techniques On Solubility, Mechanical Properties And Permeability Via Hot Melt Extrusion Technology, Eman A. Ashour

Electronic Theses and Dissertations

Hot melt extrusion (HME) was evaluated as a continuous processing technology for the manufacture of solid dispersions. The aim of the current research project was to study the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of three different grades of cellulose polymers, Klucel™ ELF, EF and LF hydroxypropylcellulose (HPC) resulting from hot melt extrusion techniques, and to assess the plasticization effect of P-CO2 on the tested polymers. The physico-mechanical properties as well as the tablet characteristics of the extrudates with and without injection of P-CO2 and with non-extruded polymers were examined. P-CO2 acted as plasticizer for Klucel™ …

Design, Synthesis, And Biological Evaluation Of Sigma Receptors (Σrs) Ligands As Potential Pharmacotherapy For Cancer And Drug Addiction, Walid Alsharif

Electronic Theses and Dissertations

Sigma receptors are a well-defined unique class of receptors and are highly expressed in the central nervous system and also widely distributed in peripheral organs and tissues. There are two subtypes of sigma receptors: sigma-1 and sigma-2. These receptors are thought to be associated with functions and disorders such as inflammation, depression, anxiety, Alzheimer’s disease, epilepsy and drug abuse. The sigma-1 receptor has been demonstrated to be involved in acute and chronic effects of cocaine and methamphetamine toxicities. However, the role of sigma-2 receptors is less clear due to the lack of availability of detailed protein structural information and truly …

Impact Of Refill Synchronization On Medication Adherence For Chronic Diseases, Divya Verma

Electronic Theses and Dissertations

Objectives: The objective of this study is to assess the impact of medication synchronization (med sync) on medication adherence for three drug classes under the CMS Star Rating system i.e. oral diabetes, hypertension and cholesterol. Methods: A quasi-experimental pre-post study design was employed using pharmacy prescription fill data from various independent community pharmacies located in different regions of Mississippi. Using Proportion of Days Covered (PDC), medication adherence before and after the med sync was calculated. Total study period of one year for each patient including six months of pre-period and post-period was used for the analysis. Descriptive statistics were calculated. …

Predictors Of Use Of Hydroxyurea And Its Impact On Clinical And Economic Outcomes Among Children With Sickle Cell Disease, Manasi Datar

Electronic Theses and Dissertations

Objective: The objective of this study was to assess the prevalence and predictors of use of hydroxyurea (HU) and its impact on clinical and economic outcomes in pediatric patients with sickle cell disease (SCD) enrolled in Medicaid. Methods: A cohort of patients with SCD was identified in 2006 using ICD-9-CM codes from Medicaid claims from 40 US states. Patients who filled three prescriptions of HU in within 6 months in 2007 were identified as HU users. HU users were then matched with non-users and the impact of HU use on the presence of crises and economic outcomes including presence of …

Study Of Novel Nanoparticle Transport And Drug Release For Cancer Treatment., Christopher Gene England 1988-

Electronic Theses and Dissertations

Nano-scale particles sized 10—400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. In this study, gold nanoparticles were functionalized with phosphatidylcholine (two-layer) or phosphatidylcholine and HDL (three-layer) in the formation of “layered” nanoparticles. The diffusivity of both two- and three layered colloidal gold nanoparticles and silica gold nanoshells were examined in 3D cell …

Extracellular Matrix Proteins And The Liver-Lung Axis In Disease., Veronica L. Massey

Electronic Theses and Dissertations

No abstract provided.

Lunasin Reduces The Melanoma Stem Cell Population In Vitro And Inhibits Tumor Proliferation In Vivo., Christopher Paul Shidal

Electronic Theses and Dissertations

Lunasin is a 44 amino acid peptide derived from the soybean seed that has been shown to have cancer chemopreventive and chemotherapeutic properties. In this study, we investigated the potential utility of lunasin as a chemotherapeutic in a melanoma model. Initial studies showed that lunasin has little activity against established melanoma cell lines in vitro using adherent culture methods; however, lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays in soft agar and oncosphere assays. These results led us to investigate whether lunasin selectively affects cancer initiating cells (CIC) that are known to be present in these melanoma …

Building A Metabolic Bridge Between Glycolysis And Sphingolipid Biosynthesis : Implications In Cancer., Morgan L. Stathem

Electronic Theses and Dissertations

Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, namely bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its role in cancer has been recognized in cancer biology over 90 years. In recent decades, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide’s essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeutic resistance. Despite this knowledge, a direct link between these two fields has yet to be concretely drawn. Herein, we show that in a model of highly glycolytic cells, generation of the …

Inducible Tumor Difference Between Rapid And Slow Rat Nat2 Congenic Fischer 344 Rats Administered Methyl-Nitrosourea., Marcus W. Stepp

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a well-known phase II metabolic enzyme that has been associated with carcinogenesis. Its role in the biotransformation of aromatic and heterocyclic amine carcinogens has been investigated for many years, but more recent investigations focus on a possible endogenous role of human NAT1 in cancer initiation and progression. We conducted in vivo studies using homozygous Fischer 344 rats, congenic at the rat Nat2 locus for high (rapid) and low (slow) activity. Wistar Kyoto inbred rats were used to breed in the slow activity rat Nat2 locus into the Fischer 344 inbred rat, which contains the …

Evaluation Of The Safety And Pharmacokinetic Profile Of The Broad Spectrum Antiviral Lectin Griffithsin., Christopher Lynn Barton

Electronic Theses and Dissertations

Carbohydrate binding agents that target viral envelope glycans are being studied for their potential use as microbicides and antiviral therapeutics. Griffithsin is a lectin originally identified in a red alga Griffithisia sp. Multiple studies have shown that GRFT inhibits HIV-1, Coronaviruses, Hepatitis C, influenza and Ebola virus replication in vitro. This antiviral activity suggests potential uses in chemoprophylaxis and disease treatment. However, safety of GRFT administration has not been extensively studied. In vivo testing--chronic subcutaneous treatment as well as single dose subcutaneous, oral, and intravenous administrations of Griffithsin in Sprague Dawley Rats (Rattus Norvegicus)--was used to assess Griffithsin’s pharmacokinetic properties …

Bone Strength And Architecture : Pharmacological Targeting Of Camkk2 As A Method For Enhancing Bone Quality., Zachary James Pritchard

Electronic Theses and Dissertations

Mice lacking or pharmacologically inhibited for calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) have enhanced bone mass and microarchitecture. This enhanced bone mass and architecture is due to changes in osteoblast and osteoclast numbers as well as activity. Whether the enhanced bone mass translated to increased bone quality and strength was further explored by developing a method to directly test the trabecular strength of the distal femur. Micro computed tomography (CT)-based measurement of the length of the epiphysis of the distal femur, aided in its removal, allowing the exposure of the trabecular bone volume used to determine the microarchitecture parameters. Following …

Preventive Effect Of Non-Mitogenic Acidic Fibroblast Growth Factor On Diabetes-Induced Testicular Cell Death., Melissa Skibba 1990-

Electronic Theses and Dissertations

Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). To assess whether nmFGF-1 protects male germ cells from diabetes-induced apoptotic death, the study employed a murine model of diabetes using multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated …

The Role Of Pesticides In Non-Alcoholic Fatty Liver Disease (Nafld)., Laila Al-Eryani 1986-

Electronic Theses and Dissertations

NAFLD, the most common form of liver disease worldwide, is caused by various factors including industrial chemicals and pesticides exposure. Annually, 5.2 billion pounds of pesticides are used worldwide and can contribute to liver disease, but their role is modestly studied. We hypothesize that pesticides contaminating food supply can worsen diet-induced steatosis via xenobiotic receptor activation. Two human and two rodent databases were utilized and 85% of the 330 chemicals identified associated with NAFLD were pesticides. Eight were selected for evaluating hepatic receptor activation in vitro. The majority including DDT activated hPXR/CAR and mPXR. DDT (100 mg/kg) was studied in …

Neurodegeneration-Associated Instability Of Ribosomal Dna., Justin Lauren Hallgren 1981-

Electronic Theses and Dissertations

Homologous recombination-mediated instability of the repetitively organized ribosomal DNA has been proposed as a mediator of cell senescence in yeast triggering the DNA damage response. High individual variability in the content of human ribosomal DNA suggests that this genomic region remained relatively unstable throughout evolution. Therefore, quantitative real time PCR was used to determine the genomic content of ribosomal DNA in post mortem samples of parietal cortex from 14 young and 9 elderly individuals with no diagnosis of a chronic neurodegenerative/neurological disease. In addition, ribosomal DNA content in that brain region was compared between 10 age-matched control individuals and 10 …

Solubility Enhancement And Precipitation Inhibition Of Poorly Water Soluble Compounds Utilizing Hot Melt Extrusion Technology, Jiannan Lu

Electronic Theses and Dissertations

Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively.

Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), …

Solubility Enhancement Via Melt Extrusion: Drug-Polymer Solubility, Physicochemical Characterization And Quality By Design, Ketaki Patwardhan

Electronic Theses and Dissertations

Many new drugs developed face oral delivery challenges and absorption due to poor biopharmaceutical properties. Formation of solid dispersions is a very widely applied technique for solubility enhancement of water insoluble drugs. In order to form stable solid dispersions it is important to select appropriate excipients that will maintain the drug in its amorphous form for an extended period of time. Selection of appropriate excipients is critical during the development of stable amorphous solid dispersions. The solubility parameter concept has been explored for theoretically identifying the excipients that will be suitable based on the structure of the active. In this …

Customer Tolerance In Community Pharmacy, Philip Everett Schwab

Electronic Theses and Dissertations

Customers can have an existing relationship with a service provider where they are not satisfied with the services they receive, yet they continue to patronize the service provider. Why does this happen? Why do these customers remain as patrons of service providers that do not meet expectations and that leave these customers with low satisfaction. This dissertation presents the concept of tolerance to explain the retention of customers who are not satisfied with a service provider. Specifically, this dissertation examined the concept of customer tolerance in community pharmacy. Tolerance is an important concept for consideration because regardless of good intentions …

Pharmacists' Preparedness For Acute Medical Emergencies, James W. Parrett

Electronic Theses and Dissertations

Purpose/Objectives: This project studied how prepared community pharmacists are to respond to acute medical emergencies, as well as their perceived efficacy in addressing these situations. Specifically, it considered what training pharmacists have for responding to medical emergencies, what emergency medical equipment pharmacies have on-hand, the frequency that medical emergencies occur within pharmacies, and the types of emergencies encountered. It also measured self and collective efficacy of pharmacists in responding to medical emergencies within their pharmacy to determine if differences in self-efficacy or collective efficacy exist. Methods: This study utilized a cross-sectional, non-experimental, descriptive design via a self-administered, Internet-based survey distributed …