Pharmacy and Pharmaceutical Sciences Commons^™

Stemming The Global Trade In Falsified And Substandard Medicines, Lawrence O. Gostin, Gillian J. Buckley, Patrick W. Kelley

Georgetown Law Faculty Publications and Other Works

Drug safety and quality is an essential assumption of clinical medicine, but there is growing concern that this assumption is not always correct. Poor manufacturing and deliberate fraud occasionally compromises the drug supply in the United States, and the problem is far more common and serious in low- and middle-income countries with weak drug regulatory systems. An Institute of Medicine consensus committee report identified the causes and possible solutions to the problem of falsified and substandard drugs around the world.

The vocabulary people use to discuss the problem is itself a concern. The word counterfeit is often used innocuously to …

Low Soluble Drug Encapsulation Based On Architecture Of Layer-By-Layer Assembly For Longer Circulation Time And Targeted Therapy, Pravin Pattekari

Doctoral Dissertations

A combined effect of sonication and layer-by-layer assembly (LbL) enhances the solubility of many poorly soluble inorganic and organic materials by forming stable particles with ca. 200 nm size and up to 90 wt% of loading. The entire method is reproducible, easy-to-handle, and flexible for varying surface properties according to the application of the materials. The method develops good colloidal stability of materials in buffers and maintains architecture for future improvement. A top-down approach, with a combined effect of sonication and LbL assembly, ruptures the material and allows adsorption of oppositely charged polyelectrolytes simultaneously. Thus, the approach is applicable for …

Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion

STAR Program Research Presentations

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

Intellectual Property And Public Health – A White Paper, Ryan G. Vacca, James Ming Chen, Jay Dratler Jr., Thomas Folsom, Timothy S. Hall, Yaniv Heled, Frank A. Pasquale, Elizabeth A. Reilly, Jeffery Samuels, Katherine J. Strandburg, Kara W. Swanson, Andrew W. Torrance, Katharine A. Van Tassel

Faculty Scholarship

On October 26, 2012, the University of Akron School of Law’s Center for Intellectual Property and Technology hosted its Sixth Annual IP Scholars Forum. In attendance were thirteen legal scholars with expertise and an interest in IP and public health who met to discuss problems and potential solutions at the intersection of these fields. This report summarizes this discussion by describing the problems raised, areas of agreement and disagreement between the participants, suggestions and solutions made by participants and the subsequent evaluations of these suggestions and solutions. Led by the moderator, participants at the Forum focused generally on three broad …

An Update On Braf Inhibitors And Other New Molecular Targets For The Treatment Of Malignant Melanoma Of The Skin, M. O. Faruk Khan, Carroll L. Ramos

Pharmaceutical Science and Research

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the …

Use Of A Subcutaneous Insulin Computerized Glucostabilizer™ Program On Glycemic Control In The Intensive Care Setting: A Retrospective Data Analysis., Sarah A. Nisly, Serena Harris, Laura Aykroyd, Joni Carrol, Brian Ulmer, Michael Waddell, Samuel Flanders, Rattan Juneja

Scholarship and Professional Work – COPHS

Background: Despite guidelines that recommend strongly against Sliding Scale Insulin (SSI) it continues to be the most commonly insulin regimen used in hospitals to treat hyperglycemia. In addition to being reactionary to a glucose that has already increased, SSI offers practical challenges in the randomness of the doses of insulin prescribed and often a disconnect with glucose testing that should be occurring in congruence to the insulin dosing. While many clinical trials have shown improved glycemic control in critical care patients receiving intravenous insulin; few studies have demonstrated the efficacy of subcutaneous (SQ) insulin in this setting. In this study, …

Canagliflozin, A New Sodium-Glucose Co-Transporter 2 Inhibitor, In The Treatment Of Diabetes, Sarah A. Nisly, Denise M. Kolanczyk, Alison M. Walton

Scholarship and Professional Work – COPHS

Purpose. The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated.

Summary. Canagliflozin belongs to a class of agents—the sodium–glucose cotransporter 2 (SGLT2) inhibitors—whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA1c) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods …

Multifunctional Hydroxyapatite And Poly(D,L-Lactide-Co-Glycolide) Nanoparticles For The Local Delivery Of Cholecalciferol, Nenad Ignjatović, Vuk Uskoković, Zorica Ajduković, Dragan Uskoković

Pharmacy Faculty Articles and Research

Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery …

Novel Therapy For Nicotine Addiction In Alcohol Dependent Rats, Bethany Ann Stennett

UNF Graduate Theses and Dissertations

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 1: Preparation And Drug Release, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the …

High-Activity Mutants Of Human Butyrylcholinesterase For Cocaine Abuse Treatment, Liu Xue

Theses and Dissertations--Pharmacy

Cocaine is a widely abused drug without an FDA-approved medication. It has been recognized as an ideal anti-cocaine medication to accelerate cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. butyrylcholinesterase (BChE)-catalyzed hydrolysis. However, the native BChE has a low catalytic activity against cocaine. We recently designed and discovered a set of BChE mutants with a high catalytic activity specifically for cocaine. An ideal, therapeutically valuable mutant of human BChE should have not only a significantly improved catalytic activity against cocaine, but also certain selectivity for cocaine over neurotransmitter acetylcholine (ACh) such …

Computational Modeling, Design, And Characterization Of Cocaine-Metabolizing Enzymes For Anti-Cocaine Medication, Lei Fang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused and addictive drug, resulting in serious medical and social problems in modern society. Currently, there is no FDA-approved medication specific for cocaine abuse treatment. The disastrous medical and social consequences of cocaine abuse have made the development of an anti-cocaine medication a high priority. However, despite decades of efforts, traditional pharmacodynamic approach has failed to yield a truly useful small-molecule drug due to the difficulties inherent in blocking a blocker like cocaine without affecting the normal functions of the transporters or receptors. An alternative approach, i.e. pharmacokinetic approach, is to interfere with the delivery of …

Towards Elucidation Of A Viral Dna Packaging Motor, Chad T. Schwartz

Theses and Dissertations--Pharmacy

Previously, gp16, the ATPase protein of phi29 DNA packaging motor, was an enigma due to its tendency to form multiple oligomeric states. Recently we employed new methodologies to decipher both its stoichiometry and also the mechanism in which the protein functions to hydrolyze ATP and provide the driving force for DNA packaging. The oligomeric states were determined by biochemical and biophysical approaches. Contrary to many reported intriguing models of viral DNA packaging, it was found that phi29 DNA packaging motor permits the translocation of DNA unidirectionally and driven cooperatively by three rings of defined shape. The mechanism for the generation …

The Pharmacokinetics Of Metal-Based Engineered Nanomaterials, Focusing On The Blood-Brain Barrier, Mo Dan

Theses and Dissertations--Pharmacy

Metal-based engineered nanomaterials (ENMs) have potential to revolutionize diagnosis, drug delivery and manufactured products, leading to greater human ENM exposure. It is crucial to understand ENM pharmacokinetics and their association with biological barriers such as the blood-brain barrier (BBB). Physicochemical parameters such as size and surface modification of ENMs play an important role in ENM fate, including their brain association. Multifunctional ENMs showed advantages across the highly regulated BBB. There are limited reports on ENM distribution among the blood in the brain vasculature, the BBB, and brain parenchyma.

In this study, ceria ENM was used to study the effect of …

Formulation Optimization For Pore Lifetime Enhancement And Sustained Drug Delivery Across Microneedle Treated Skin, Priyanka Ghosh

Theses and Dissertations--Pharmacy

Microneedle (MN) enhanced drug delivery is a safe, effective and efficient enhancement method for delivery of drug molecules across the skin. The “poke (press) and patch” approach employs solid stainless steel MN to permeablize the skin prior to application of a regular drug patch over the treated area. It has been previously shown that MN can be used to deliver naltrexone (NTX) at a rate that provides plasma concentrations in the lower end of the therapeutic range in humans. The drug delivery potential of this technique is, however, limited by the re-sealing of the micropores in a 48-72h timeframe. The …

Nanoparticles Of Cobalt-Substituted Hydroxyapatite In Regeneration Of Mandibular Osteoporotic Bones, Nenad Ignjatović, Zorica Ajduković, Vojin Savić, Stevo Najman, Dragan Mihailović, Perica Vasilijević, Zoran Stojanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 2: Antibacterial And Osteoblastic Response, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time …

Preparasi, Karakterisasi Dan Evaluasi Pelepasan Obat Dari Beads Kalsium Alginat Deksametason Dengan Metode Gelasi Ionik, Christye Aulia, Joshita Djajadisastra

Majalah Ilmu Kefarmasian

Inflammatory Bowel Disease (IBD) is a disease of inflammation in the colon. Targeted delivery systems for the treatment of IBD is designed to increase the drug concentration in the local tissue. Dexamethasone is a drug having anti-inflammatory and antifibrosis effects which is used to repair scar tissue arising from postoperative IBD. This research purpose to create calciumalginate beads dexamethasone to be released only in the colon. Beads were made by using sodium-alginate and Ca2+ as crosslinker by ionic gelation method, with ratio between sodium alginate-dexamethasone (3:1). A concentration of solution sodium alginate 3 % b/v with variation concentration of crosslinker …

Effect Of Compression Force On Agglomeration Of Micronized Active Pharmaceutical Ingredients: Techniques To Prevent Api Agglomeration During Compression, Suresh Potharaju

Theses and Dissertations (ETD)

Micronization is one of the common processes for size reduction to increase surface area of poorly soluble Active Pharmaceutical Ingredient’s (API). This size reduction improves the dissolution rate and permeability thereby increasing the bioavailability for hydrophobic API’s.

Tablets and capsules are the most marketed and easy to manufacture solid dosage forms. During manufacturing of tablets, high compression forces are applied uniaxially on the powder bed to get a coherent consolidated compact with good tensile strength. So, diluents are required to mix with API’s and compress into tablets. When this mixture is compressed into tablets, there is a possibility of agglomeration …

Nanotherapies For Treating Prostate Cancer, Michael Danquah

Theses and Dissertations (ETD)

Current prostate cancer treatment remains ineffective primarily due to ineffectual therapeutic strategies and numerous tumor-associated physiological barriers which hinder efficacy of anticancer agents. Therefore, the focus of this study was to investigate a new combination therapy approach for treating prostate cancer and develop polymeric nanocarriers to facilitate anticancer drug and nucleic acid delivery.

It was hypothesized that simultaneously targeting androgen-androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) signaling pathways would be effective in treating prostate cancer. The effect of bicalutamide (antiandrogen) and embelin (XIAP inhibitor) on the growth of prostate cancer cells in vitro and in vivo was …

Development Of The Sustained Release Analgesic Formulations For Rodents And A Novel In Vitro Model For Parenteral Formulations With The Character Of A Level A Ivivc, Jin Xu

Theses and Dissertations (ETD)

Laboratory animals are often subjected to various painful surgical procedures such as laparotomy, thoracotomy or orthopedic procedures as well as non-surgical procedures such as the induction of arthritis. Any procedure that causes pain in humans is assumed to cause pain in animals too. It is the ethical obligation of all research personnel to reduce or preferably eliminate pain and distress by using analgesics. Furthermore, the Institutional Animal Care and Use Committee (IACUC) requires that appropriate anesthetics and/or analgesics must be used to minimize or eliminate pain and distress for animals undergoing painful procedures.

The oral administration route is the most …

Anti-Cancer Drug Screening Of Dual Tubulin And Hsp27 Inhibitors With 2d And 3d Lung Cancer Cell Assays, Janine Maria Naim, Rati Lama

Undergraduate Research Posters 2012

Cancer is the leading cause of death worldwide. The current treatment options available for lung cancer are limited and have drawbacks such as poor bioavailability, numerous side effects, poor efficacy and drug resistance. 3D model serve as a novel approach for drug screening purposes and the evaluation of compounds in the platform can help identify potent compounds for further in vivo xenograft studies.

Uji Penghambatan Aktivitas Alfa-Glukosidase Ekstrak Dan Fraksi Daun Antidesma Montanum Blume, Nofiantini Nofiantini, Berna Elya, Azizahwati Azizahwati

Majalah Ilmu Kefarmasian

alpha-Glucosidase inhibitor has known to be a therapeutic agent for diabetes mellitus (DM) treatment, especially type 2 DM. Based on previous studies. There are various plants that have the effect of inhibiting the activity of a-glucosidase, one of which is garu leaves (Antidesma montanum Blume). This research aimed to get the fraction which had the highest Il-glucosidase inhibiting activity from ethanol extract of garu leaves and identify the chemical compounds from the most active fraction. Simplisia powder was extracted by maseration using 80% ethanol then fractionated using n-hexane, ethyl acetate, and methanol. Inhibitory activity test was performed by measuring absorbance …

Analisis Zat Warna Merah Sintetik Pada Selai Stroberi Yang Dijual Di Pasar Tradisional Kota Depok, Putri Ayuningtyas, Rani Sauriasari, Maryati Kurniadi

Majalah Ilmu Kefarmasian

Jam is a semi-solid food products made of fruit cooked with sugar that used as aflavoring on bakery including strawberry jam. Strawberry jam is added to food additives such as food dyes. The purpose of this study is to know about ponceau 4R, allura red, rodamin B, and amaran in the sample of strawberry jam in the traditional market at Depok City and to determine the levels of synthetic red dyes that are permitted on the sample strawberry jam. The method applied was dye isolation with wool and followed by analysis using a color reaction, then followed by paper chromatography …

Uji Stabilitas Fisik Dan Aktivitas Antioksidan Formula Krim Yang Mengandung Ekstrak Kulit Buah Delima, Joshita Djajadisastra, Juheini Amin

Majalah Ilmu Kefarmasian

Delima (Punica granatum L) merupakan salah satu buah memiliki aktivitas antioksidan yang kuat karena mengandung senyawa flavanoid dan tannin seperti asam elagic, asam gallat, punicalin, punicalagin, anthocianin, elligatanin, gallotanin, kuersetin, katekin. Senyawa—senyawa ini diketahui dapat mencegah dan menghambat terbentuknya radikal bebas yang penyebabkan penuaan dini dan penyakit kronis. Dalam penelitian ini ekstrak kulit buah delima diformulasikan dalam bentuk krim yang dibedakan kandungan nya yaitu konsentrasi 0, 75%, 1%, 2%. Uji kestabilan fisik dilakukan dengan penyimpanan sediaan pada tiga suhu yaitu suhu kamar; suhu 40C; 40,2 C, uji mekanik dan cycling test. Hasil penelitian ini menunjukkkan bahwa krim ekstrak kulit buah …

Uji Efek Analgesik Ekstrak Etanol Mencit Jantan Dengan Metode Tail-Flick, Widiarti Widiarti, Retnosari Andrajati, Juheini Amin

Majalah Ilmu Kefarmasian

In the previous study the analgesic effect of Cinnamommum zeylanicum Breyn had been investigating. The aim of this study was to investigate analgesic effect of the 70% ethanol extract of cinnamon bark (Cinnamommum zeylanicum Breyn.). This study used Tail Flick method at 25 male mice which have passed sensitivity test, divided into five groupes. Group I as negative control was administered 0,5% CMC, group Il as positive control was administered tramadol HCI, group Ill, IV and V was administered extract of cinnamon bark at 8; 16 and 32 mg/20 g BW. Drugs were orally administered to mice. The reaction of …

Seleksi Galur-Galur Leuconostoc Yang Mempunyai Aktivitas Bakteriostatin Terhadap Berbagai Bakteri Indikator, Agustina Retnaningsih, Amarila Malik, Maksum Radji

Majalah Ilmu Kefarmasian

Lactid Acid Bacteria (LAB) are known to produce bacteriocins which have antimicrobial activity, and possessed to be developed as antibiotic complement. This study aimed to characterize bacteriocins activity from Leuconostoc strains isolated previously from local sources, and to optimize pH and incubation temperature as well. A well diffusion agar assay for zone inhibition method and bacteriocin potency assay performing minimum inhibition concentration (MIC) have been done. Bacterial indicators used in this study are Leu. mesenteroides TISTR 120, and JCM 6124, Staphylococcus aureus FNCC 0047, Listeria monocytogenes FNCC 0156, Escherichia coli FNCC 0183, Pseudomonas aeruginosa FNCC 0063, Salmonella typhi FNCC 0165 …

Discovery Of Dihydroartemisinin And Dasatinib Drug Combination To Cure Pooroutcome Bcr-Abl+ Acute Lymphoblastic Leukemia, Harpreet Singh

Theses and Dissertations (ETD)

Oncogenic signaling by the Philadelphia chromosome-encoded BCR-ABL fusion kinase initiates and drives both Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Food and Drug Administration (FDA)- approved BCR-ABL-specific kinase inhibitors (BCR-ABL–KIs) imatinib, dasatinib and nilotinib induce prolonged remissions in CML but poor leukemia-reduction and relapse-control in Ph+ ALL. The relative primary BCR-ABL–KI-resistance in Ph+ ALL patients carrying predominantly BCR-ABLWT disease cannot be attributed to drug-resistant BCR-ABL mutations (BCR-ABLMUTANTS), and remains poorly understood.

We established a cell-based platform to evaluate the modulation of anti-Ph+ ALL activity of drugs by both tumor-extrinsic cytokines normally present in the leukemia …

Investigation Of Enhancement Of Furosemide Solubilization With Cyclodextrins And A Novel Octenyl Succinate Anhydride Starch, Rui Zhu

Theses and Dissertations (ETD)

Solubility behavior is one of the most challenging aspects for drug commercialization and often the main reason of drug that do not reach to its full potential. Now nearly 60% new chemical entities possess solubility problems, whereas practically no drug products with less than 10 µg/ml solubility in 70’s or 80’s. There is an ever increasing need to develop new formulation techniques and exicipients with novel mechanisms of action. Various techniques have been applied to enhance the drug solubility such as co-solvents, particle size reduction, lipid based drug delivery systems, nanosuspension, use of surfactants, salt formation, cyclodextrin complexes and solid …

Targeting Traf6 For Cancer Therapeutical Development, John K. Morrow

Dissertations and Theses (Open Access)

Tumor necrosis factor (TNF)-Receptor Associated Factors (TRAFs) are a family of signal transducer proteins. TRAF6 is a unique member of this family in that it is involved in not only the TNF superfamily, but the toll-like receptor (TLR)/IL-1R (TIR) superfamily. The formation of the complex consisting of Receptor Activator of Nuclear Factor κ B (RANK), with its ligand (RANKL) results in the recruitment of TRAF6, which activates NF-κB, JNK and MAP kinase pathways. TRAF6 is critical in signaling with leading to release of various growth factors in bone, and promotes osteoclastogenesis. TRAF6 has also been implicated as an oncogene in …