Pharmacy and Pharmaceutical Sciences Commons^™

Crystalline Salt Formation Of An Acidic Drug Indomethacin Using Hot Melt Extrusion Technology, Mustafa Bookwala

Electronic Theses and Dissertations

Although salt formation is the most ubiquitous and effective method of increasing the solubility and dissolution rates of acidic and basic drugs, it consumes large quantities of organic solvents and is a batch process. Herein, we show that the dissolution rate of indomethacin (a poorly water-soluble drug) can be increased by using hot melt extrusion of a 1:1 (mol/mol) indomethacin:tromethamine mixture to form a highly crystalline salt, the physicochemical properties of which are investigated in detail. Specifically, pH–solubility studies demonstrated that this salt exhibited a maximal solubility of 19.34 mg/mL (>1000 times that of pure indomethacin) at pH 8.19. …

A Novel Acetaminophen Soft-Chew Formulation Produced Via Hot Melt Extrusion With Inline Near-Infrared Monitoring As A Process Analytical Technology Tool, Pengchong Xu

Electronic Theses and Dissertations

People suffer dysphagia when swallowing hard tablets and capsules. Gelatin based soft chewable tablets was used as an alternative and novel drug delivery format to overcome dysphagia. But conventional method of producing gelatin based soft chewable tablets has many potential issues. The objective of this study is using glycerol and hot-melt extrusion technique to address potential issues and optimizing the formulation. Gelatin (15%), acetaminophen (30%), saccharin (1.5%), xylitol (6.5%), sodium chloride (2%) and six different ratios of water (45-0%) and glycerol (0-45%) were used in seven formulations. The extrusion process temperature of formulation 1-6 and formulation 7 were 90 ëšc …

The Prevention And Control Of Cancer By Metformin In Patients With Type 2 Diabetes: A Systematic Mapping Review Protocol, Michelle Price, Gabriela Cipriano, Albania Mitchell

Lavery Library Faculty/Staff Publications

No abstract provided.

Association Between Dispensing Channel And Chronic Obstructive Pulmonary Disorder Exacerbations Among Medicare Beneficiaries, April S. Prather

Theses and Dissertations--Pharmacy

Elderly patients with chronic obstructive pulmonary disease may be at increased risk of exacerbation due to physical and cognitive deficits that make proper inhaled medication adherence more difficult despite consistent medication access. This retrospective study utilized administrative medical and pharmacy claims data to examine the likelihood of having a COPD exacerbation requiring acute medical care by means of an emergency room visit or hospitalization in elderly patients receiving maintenance COPD medications from mail order and retail pharmacies. It was hypothesized that mail order patients would be more likely to experience exacerbations despite differences in medication access when compared to retail …

Exploring The Effect Of Chronic Inflammation On Response To Immune Checkpoint Inhibitors In Cancer, Sherif M. El-Refai

Theses and Dissertations--Pharmacy

Precision medicine has allowed for the development of monoclonal antibodies that unmask the anti-tumor immune response. These agents have provided some patients durable clinical benefit. However, PD-1 and PD-L1 inhibitor therapies are effective in a small group (10-20%) of non-small cell lung cancer (NSCLC) patients when used as single-agent therapy. The approved companion diagnostic is expression of the immune cell surface molecule, programmed death ligand 1 (PD-L1), on tumors measured by immunohistochemistry (IHC). Studies in tumor biology and immune surveillance dictate that PD-1 inhibitor efficacy should depend on the level of PD-L1 expression; however, the literature has not followed with …

Dual Lox/Cox Inhibition: A Novel Strategy To Prevent Neurovascular Leakage In Epilepsy, Brent S. Sokola

Theses and Dissertations--Pharmacy

Epilepsy affects 3.4 million patients in the USA and is characterized by recurring seizures. The blood-brain barrier is leaky in epilepsy and may contribute to seizure progression but the mechanisms which cause this leakage are not fully understood. We hypothesized that seizures trigger LOX- and COX-mediated blood-brain barrier leakage and that dual LOX/COX inhibition prevents barrier leakage in vivo. To test this hypothesis, we administered either the dual LOX/COX inhibitor licofelone or a combination of the 5-LOX inhibitor zileuton and the COX-2 inhibitor celecoxib to rats that experienced status epilepticus (SE). Serum and brain capillaries were isolated 48 hours …

Investigating The Role Of Prescription Drug Monitoring Programs In Reducing Rates Of Opioid-Related Poisonings, Nathan James Pauly

Theses and Dissertations--Pharmacy

The United States is in the midst of an opioid epidemic. In addition to other system level interventions, almost all states have responded to the crisis by implementing prescription drug monitoring programs (PDMPs). PDMPs are state-level interventions that track the dispensing of Controlled Substances. Data generated at the time of medication dispensing is uploaded to a central data server that may be used to assist in identifying drug diversion, medication misuse, or potentially aberrant prescribing practices.

Prior studies assessing the impact of PDMPs on trends in opioid-related morbidity have often failed to take into account the wide heterogeneity of program …

Understanding The Thermodynamics And Oral Absorption Potential Of Pharmaceutical Amorphous Solid Dispersions, Nico Setiawan

Theses and Dissertations--Pharmacy

Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such …

Using Machine Learning To Predict Acute Kidney Injuries Among Patients Treated With Empiric Antibiotics, Wilbur Cliff Rutter Iv

Theses and Dissertations--Pharmacy

Acute kidney injury (AKI) is a significant adverse effect of many medications that leads to increased morbidity, cost, and mortality among hospitalized patients. Recent literature supports a strong link between empiric combination antimicrobial therapy and increased AKI risk. As briefly summarized below, the following chapters describe my research conducted in this area.

Chapter 1 presents and summarizes the published literature connecting combination antimicrobial therapy with increased AKI incidence. This chapter sets the specific aims I aim to achieve during my dissertation project.

Chapter 2 describes a study in which patients receiving vancomycin (VAN) in combination with piperacillin-tazobactam (TZP) or cefepime …

The Impact Of Bioactive Phytosterol, Stigmasterol, On Cholesterol Elimination Pathways In Mice, Hannah C. Lifsey

Theses and Dissertations--Pharmacy

Despite advances in healthcare, cardiovascular disease (CVD) remains the leading cause of death in the United States. Elevated levels of plasma cholesterol are highly predictive of CVD and stroke and are the principal driver of atherosclerosis. Unfortunately, current cholesterol lowering agents, such as statins, are not known to reverse atherosclerotic disease once it has been established. In preclinical models, agonists of nuclear receptor, LXR, have been shown to reduce and reverse atherosclerosis. Phytosterols are bioactive non-cholesterol sterols that act as LXR agonists and regulate cholesterol metabolism and transport. We hypothesize that stigmasterol would act as an LXR agonist and alter …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic …

Using The Qbest Equation To Evaluate Ellagic Acid Safety Data: Generating A Qnoael With Confidence Levels From Disparate Literature, Cynthia Rose Dickerson

Theses and Dissertations--Pharmacy

QBEST, a novel statistical method, can be applied to the problem of estimating the No Observed Adverse Effect Level (NOAEL or QNOAEL) of a New Molecular Entity (NME) in order to anticipate a safe starting dose for beginning clinical trials. The NOAEL from QBEST (called the QNOAEL) can be calculated using multiple disparate studies in the literature and/or from the lab. The QNOAEL is similar in some ways to the Benchmark Dose Method (BMD) used widely in toxicological research, but is superior to the BMD in some ways. The QNOAEL simulation generates an intuitive curve that is comparable to the …

Synthesis And Biological Evaluation Of Novel Drug Candidates To Address Drug Resistance In Tuberculosis And Fungal Diseases, Huy Ngo

Theses and Dissertations--Pharmacy

Tuberculosis (TB) and fungal infections are two of the most lethal infectious diseases worldwide due to the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) and fungal strains that can resist the most potent antimicrobial drugs currently employed. Due to the rise of these drug resistant strains, effective treatment options for these two infections are limited. This dissertation aims at exploring novel drug scaffolds to help combat drug resistance in TB and fungal infections.

TB caused by the pathogenic Mtb is, alongside with human immunodeficiency virus acquired immunodeficiency virus (HIV), the deadliest infectious disease worldwide with approximately 2-3 billion people …

Nsu Sharks Rx-Winter, 2018, Nova Southeastern University

NSU Sharks Rx

No abstract provided.

Scalable Feature Selection And Extraction With Applications In Kinase Polypharmacology, Derek Jones

Theses and Dissertations--Computer Science

In order to reduce the time associated with and the costs of drug discovery, machine learning is being used to automate much of the work in this process. However the size and complex nature of molecular data makes the application of machine learning especially challenging. Much work must go into the process of engineering features that are then used to train machine learning models, costing considerable amounts of time and requiring the knowledge of domain experts to be most effective. The purpose of this work is to demonstrate data driven approaches to perform the feature selection and extraction steps in …

Impact Of Rapid Identification Of Gram Negative Blood Cultures In A Community Hospital System, Carley Thompson Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Impact Of Body Weight On Hemodynamic Response To Fixed Dose Vasopressin In Septic Shock, Corissa Piatka

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Implementation Of Non-Opioid Order Panels In Parkview Health Emergency Departments, Brandon James Euen

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Hypothermia Protocol, Jason Eakins Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Evaluation Of A Hospital-Based Pharmacist-Driven Transitions Of Care Service, Jordan Holder Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Vancomycin Dosing: Bayesian Derived Auc/Mic Vs. Trough Only Monitoring, Meagan Ellinger Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Impact Of Customized Response Options On Medication Alert Salience, Alissa Keillor Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Evaluation Of Pharmacist Involvement In Outpatient Transitional Care Management, Katharine Lundy Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Implementation Of A Pilot Program For Medication-Assisted Treatment In The Emergency Department, Jenna Deininger Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

Intranasal Administration Of A Two-Dose Adjuvanted Multi-Antigen Tmv-Subunit Conjugate Vaccine Fully Protects Mice Against Francisella Tularensis Lvs Challenge, Alison A. Mccormick, Aisha Shakeel, Chris Yi, Hardeep Kaur, Ahd M. Mansour, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Tularemia is a fatal human disease caused by Francisella tularensis, a Gram-negative encapsulated coccobacillus bacterium. Due to its low infectious dose, ease of aerosolized transmission, and lethal effects, the CDC lists F. tularensis as a Category A pathogen, the highest level for a potential biothreat agent. Previous vaccine studies have been conducted with live attenuated, inactivated, and subunit vaccines, which have achieved partial or full protection from F. tularensis live vaccine strain (LVS) challenge, but no vaccine has been approved for human use. We demonstrate the improved efficacy of a multi-antigen subunit vaccine by using Tobacco Mosaic virus (TMV) as …

Pharmacy Technician-Administered Vaccines: On Perceptions And Practice Reality, Alex J. Adams, Shane P. Desselle, Kimberly C. Mckeirnan

Faculty Publications & Research of the TUC College of Pharmacy

Doucette and Schommer recently surveyed U.S. community pharmacy technicians on their willingness to perform tasks including the administration of vaccines. They found that 47.1% of technicians reported they were “unwilling” to administer a vaccine, although this finding must be placed into proper context. The first nationwide survey of U.S. pharmacist perceptions on immunizations in 1998 revealed only 2.2% of pharmacist respondents had administered adult vaccines and only 0.9% had administered childhood vaccines. They also found pharmacists to be “slightly negative on administering immunizations” with many perceived barriers. Nonetheless, pharmacist-provided immunizations have been an unqualified public health success. The theory of …

Impact Of Clinical Guideline Implementation Of Adult Ketamine Dosing In The Emergency Department, Julia Dickman Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018