Pharmacy and Pharmaceutical Sciences Commons^™

Modeling, Optimization, And Sensitivity Analysis Of A Continuous Multi-Segment Crystallizer For Production Of Active Pharmaceutical Ingredients, Bradley James Ridder

Open Access Dissertations

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the …

Expression Of The Nkcc2a Cotransporter In Mouse Central Nervous System, Katherine E. Fahy, James B. Lucot, Hayo Castrop, Mauricio Di Fulvio

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

Na-K-2Cl cotransporter 2A (NKCC2A), also known as the bumetanide-sensitive cotransporter 1 (BSC1), transports Na+, K+ and Cl- with a stoichiometry of 1:1:2. NKCC2A is considered a kidney specific cotransporter. It is abundantly expressed in apical membrane of the tubular cells in the thick ascending limb of the loop of Henle (TALH) and in the macula densa. However, NKCC2 has also been found at low levels in different cells, including insulin-secreting ones. This secondary active transporter uses the energy stored in the electrochemical gradients of Na and K maintained by the Na/K-ATPase located on the basolateral membrane of the TALH. The …

Analysis Of Humira, Electro-Acupuncture, And Pulsatile Dry Cupping On Reducing Joint Inflammation In Patients With Rheumatoid Arthritis, Natalie Noll

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from rashes to skin cancer. Humira works by blocking the chemical receptor RANKL which inhibits the production of osteoclasts. Osteoclasts are cells that attack and eat bone and cartilage therefore an inhibitory mechanism would cause inflammation.. By analyzing Humira’s effect on the human body, Humira can be compared to other treatments such as electro-acupuncture and pulsatile dry cupping to determine the viability of these alternative treatment methods in regards to their abilities to decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL. An analysis …

Economic Impact Of Waste In Prescribing, Dispensing, And Medication Consumption In The United States, Sarah Almanie

Theses and Dissertations

Abstract

ECONOMIC IMPACT OF WASTE IN PRESCRIBING, DISPENSING, AND MEDICATION CONSUMPTION IN THE UNITED STATES

By Sarah A. Almanie, M.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2015.

Major Director: David A. Holdford, R.Ph., M.S., Ph.D., FAPhA

Professor

Department of Pharmacotherapy and Outcomes Science

OBJECTIVES: This research examines waste associated with the medication use process which consists of unfilled prescriptions, abandoned prescriptions, or unused prescription medications. The aim of this study is to quantify the direct medical costs of medication waste in delivery of …

Nosh-Aspirin (Nbs-1120), A Dual Nitric Oxide And Hydrogen Sulfide-Releasing Hybrid, Reduces Inflammatory Pain, Miriam D. Fonseca, Fernando Q. Cunha, Khosrow Kashfi, Thiago M. Cunha

Publications and Research

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dosedependent (5–150 lmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin’s antinociceptive effect was also …

A Randomized Prospective Study On Outcomes Of An Empathy Intervention Among Second-Year Student Pharmacists, Kajua B. Lor, Julie T. Truong, Eric J. Ip, Mitchell J. Barnett

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To determine the impact of a single, 3-day intervention on empathy levels as measured by the validated Jefferson Scale of Empathy-Health Profession Students version (JSE-HPS).

Methods. Forty second-year student pharmacists were recruited to participate in a non-blinded prospective study. Subjects were randomized to an intervention group (n=20) or control group (n=20) and completed the JSE-HPS at baseline, 7 days postintervention, and 90 days postintervention. The intervention group consisted of a 3-day simulation, each day including a designated activity with loss of dominant hand usage, vision, and speech.

Results. The 3-day simulation increased empathy levels in the intervention group compared …

Pharmdigest Volume 2, Issue 2, Philadelphia College Of Osteopathic Medicine, School Of Pharmacy

PharmDigest

This issue of the Pharmacy Student Council newsletter includes the following articles:

• Journey to Pharmacy
• Live Your Why
• Daily Dose: Compounding
• Research Lab
• Let's Get Clinical

Scientific And Regulatory Policy Committee (Srpc) Review*: Interpretation And Use Of Cell Proliferation Data In Cancer Risk Assessment, Charles E. Wood, Renee R. Hukkanen, Radhakrisha Sura, David Jacobson-Kram, Thomas Nolte, Marielle Odin, Samuel M. Cohen

United States Food and Drug Administration: Publications

Increased cell proliferation is a central key event in the mode of action for many non-genotoxic carcinogens, and quantitative cell proliferation data play an important role in the cancer risk assessment of many pharmaceutical and environmental compounds. Currently, there is limited unified information on assay standards, reference values, targeted applications, study design issues, and quality control considerations for proliferation data. Here, we review issues in measuring cell proliferation indices, considerations for targeted studies, and applications within current risk assessment frameworks. As the regulatory environment moves toward more prospective evaluations based on quantitative pathway-based models, standardiza- tion of proliferation assays will …

Discovery Of Alternative Artemisinin Binding Sites In Plasmodium Falciparum Atpase-6, Shuneize Elizabeth Slater

Electronic Theses and Dissertations

Malaria is a fatal yet preventable and treatable disease. It is commonly spread through the bite of an infected Anopheles mosquito. Malaria parasites belong to the Plasmodium genus and can be caused by the falciparum, malariae, ovale, vivax, and knowlesi species. Artemisinin is an endoperoxide lactone extracted from qinghaosu (Artemisia annua L. or sweet wormwood). It and its derivatives possess uncharacteristically rapid action against Plasmodium falciparum. Artemisinin is unique in its effectiveness in deadly cerebral malaria. The endoperoxide bridge is crucial for its antimalarial activity; however, how it aids in killing the parasite is unknown. While there are multiple suggested …

Health Utility Assessment Among Caregivers Of Individuals With Multiple Sclerosis, Namita Joshi

Electronic Theses and Dissertations

OBJECTIVES The study objectives were to evaluate psychometric properties of the EuroQoL–five–dimensional questionnaire (EQ–5D–3L) among caregivers of individuals with multiple sclerosis (MS), assess caregiver utilities and determine predictors of utilities, and compare caregiver utilities obtained from the EQ–5D–3L and the SF–6D. METHODS A web–based survey was administered to MS caregivers via Qualtrics survey software using assistance from a MS patient registry– North American Research Committee on MS (NARCOMS). Measurement properties including convergent, discriminant, and known–groups validity, reliability, and ceiling and floors effects of the EQ–5D–3L were tested. Caregiver health utilities were estimated using the EQ–5D–3L and compared with population norms; …

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 …

Survey Evaluation Of Pharmacy Practice Involving Deaf Patients, Mckenzie C. Ferguson, Leah M. Shan

Pharmacy Faculty Research, Scholarship, and Creative Activity

For a patient that is deaf, providing patient care can be more difficult due to communication barriers. This study was conducted in order to better understand pharmacists’ current means of communicating with deaf patients as well as investigating pharmacists’ knowledge of their legal responsibility to these patients.

Methods

Surveys were used to gather information from pharmacists and were distributed in areas with a large population of deaf patients.

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.

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Roles Of Abcg5 Abcg8 Cholesterol Transporter In Lipid Homeostasis, Yuhuan Wang

Theses and Dissertations--Pharmacy

The ABCG5 ABCG8 (G5G8) sterol transporter promotes cholesterol secretion into bile and opposes dietary sterol absorption in the small intestine. An emerging body of literature suggests that G5G8 links sterol flux to various risk factors for metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). Therapeutic approaches that accelerate G5G8 activity may augment reverse cholesterol transport (RCT) and provide beneficial effects in the prevention and treatment of cardiovascular and liver disease.

Mice lacking leptin (ob/ob) or its receptor (db/db) are obese, insulin resistant in part due to the reduced levels of hepatic G5G8 and biliary cholesterol. …

Medication Misadventures: The Case Of Benzodiazepines, Sarah E. Wixson

Theses and Dissertations--Pharmacy

For patients afflicted with symptoms of anxiety and insomnia, benzodiazepines are generally a safe and effective short-term pharmacological treatment option. Although considered safer than other sedative-hypnotic medications, substantial concern exists regarding the addictive nature and abuse potential of benzodiazepines along with potentially inappropriate prescribing and utilization in clinically vulnerable populations. These medication misadventures can have a significant impact on public health. Examples of medication misadventures as they pertain to benzodiazepines include the prescribing and use in clinically vulnerable populations for whom they are contraindicated or their efficacy has not been evaluated, the development of tolerance or addiction, abuse of the …

Kinetics And Mechanisms Of Crystal Growth Inhibition Of Indomethacin By Model Precipitation Inhibitors, Dhaval D. Patel

Theses and Dissertations--Pharmacy

Supersaturating Drug Delivery Systems (SDDS) could enhance oral bioavailability of poorly water soluble drugs (PWSD). Precipitation inhibitors (PIs) in SDDS could maintain supersaturation by inhibiting nucleation, crystal growth, or both. The mechanisms by which these effects are realized are generally unknown. The goal of this dissertation was to explore the mechanisms underpinning the effects of model PIs including hydroxypropyl β-cyclodextrins (HP-β-CD), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP) on the crystal growth of indomethacin, a model PWSD. At high degrees of supersaturation (S), the crystal growth kinetics of indomethacin was bulk diffusion-controlled, which was attributed to a high energy form deposited …

Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

A Molecular-Level View Of The Physical Stability Of Amorphous Solid Dispersions, Xiaoda Yuan

Theses and Dissertations--Pharmacy

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization …

Molecular And Functional Investigation Of Cancer-Type And Liver-Type Variants Of Organic Anion Transporting Polypeptide 1b3, Nilay Thakkar

Theses and Dissertations--Pharmacy

OATP1B3 belongs to the OATP (organic anion transporting polypeptides) superfamily, responsible for mediating the transport of various endogenous and xenobiotic substrates. OATP1B3 was initially reported to be expressed exclusively in the hepatocytes where it mediates the uptake of numerous endogenous substrates (e.g. bile acids, steroid hormone conjugates) and several clinically relevant drugs including anticancer drugs. Later, a number of studies reported that OATP1B3 is also frequently expressed in multiple types of cancers and may be associated with differing clinical outcomes. However, a detailed investigation on the expression, localization and functions of OATP1B3 expressed in cancer has been lacking. In this …

Antibiotics Targeting Tuberculosis: Biosynthesis Of A-102395 And Discovery Of Novel Actinomycins, Wenlong Cai

Theses and Dissertations--Pharmacy

The increase in antibiotic resistance of many bacterial strains including multidrug-resistant tuberculosis (MDR-TB) due to over- and misuse of antibiotics is a serious medical and economical problem. Therefore discovery and development of new antibiotics are urgently needed. Two projects were undertaken to address the need for new anti-tuberculosis antibiotics.

1. Discovery of new chemical entities. A-102395, a new nucleoside inhibitor of bacterial MraY (translocase I, EC 2.7.8.13) that is essential for bacterial survival, was isolated from the culture broth of Amycolatopsis sp. SANK 60206 in 2007. Although A-102395 is a potent inhibitor of translocase I with IC50 of 11 nM, …

Elucidating The Mechanism Of Lipl: A Non-Heme Fe(Ii), Α -Ketoglutarate: Uridine-5’-Monophosphate Dioxygenase, Anwesha Goswami

Theses and Dissertations--Pharmacy

Several nucleoside natural product antibiotics from Streptomyces sp. and actinomycetes have recently been shown to target bacterial peptidoglycan cell wall biosynthesis by inhibiting the bacterial translocase I (MraY). The biosynthetic gene clusters for A-90289, liposidomycins and caprazamycins revealed a protein with sequence similarity to proteins annotated as α-KG:taurine dioxygenases (TauD). This enzyme (LipL) is a mononuclear, non-heme, Fe(II) dependent α-keto glutarate (α-KG) :uridine monophosphate (UMP) dioxygenase responsible for the net dephosphorylation and two electron oxidation of UMP to uridine-5’-aldehyde. The postulated reaction coordinates involving the activation of the C-5’ center in UMP and the corresponding formation of uridine-5’-aldehyde are modeled …

Mucosal Delivery Of Particulate Breast Cancer Vaccine, Lipika Chablani, Nihal S. Mulla, Periasamy Selvaraj, Martin J. D'Souza

Pharmacy Faculty/Staff Publications

Vaccination has been widely used as a mode of protection against various diseases by taking advantage of host's immune system. Even though vaccination has provided relief from many infectious diseases, vaccination for cancer still remains a challenge. Cancer is caused by mutated cell functioning leading to uncontrolled growth in the organ of genesis and further possible metastasis worsens the situation. In spite of various current therapies such as surgery, chemotherapy and radiation therapy, we are still lacking behind in the race with this evolving disease. There are two major approaches for vaccination: prophylactic or therapeutic. Prophylactic vaccines find their applications …

Drug-Excipient Compatibility Studies In Formulation Development: Current Trends And Techniques, Vivek S. Dave, Rahul V. Haware, Nikhil A. Sangave, Matt Sayles, Michael Popielarczyk

Pharmacy Faculty/Staff Publications

The safety, efficacy, quality and stability of a formulation are the cornerstones of any new drug development process. In order to consistently maintain these attributes in a finished dosage form, it is important to have a comprehensive understanding of the physico-chemical characteristics of the active pharmaceutical ingredient (API), as well as all other components (e.g. excipients, manufacturing aids, packaging materials) of the drug product. In a new drug development process, a detailed characterization of the API and other formulation components is usually carried out during the preformulation stage. The preformulation stage involves characterization of several aspects of the API including …