Pharmaceutics and Drug Design Commons^™

Biophysical And Biochemical Screening Approaches For Antimicrobial Drug Discovery Targeting S. Aureus Clpp, Aman Preet Singh

Theses and Dissertations (ETD)

The discovery of antibacterial drugs has been among most significant achievements of mankind in saving millions of lives across the planet from infectious diseases. With rise in resistance to almost all existing chemotypes, the design of next generation novel antibiotics has become much more challenging and difficult. The early 21st century witnessed the advancement of multiple novel chemotypes during golden age of antibiotics however the pace of antibiotic drug discovery has slowed down tremendously, contributing to life threatening antimicrobial discovery void since 1980’s. Therefore the need to develop novel antibiotics with unique mechanism of action to leverage against multi drug …

The Development Of Methods To Account For Physiologic Dynamic Changes And Their Effects On The Pharmacokinetics Of Therapeutic Monoclonal Antibodies And Other Therapeutics, Josiah Thomas Ryman

Theses and Dissertations (ETD)

Physiologic changes in the body can drastically affect the clearance of a medication, and therefore increase the variability in exposure to the medication. Physiologic changes that can have a profound effect on the exposure of a medication can stem from changes CYP enzymes, transport proteins, binding protein expression, organ function, immune reactivity, and health status to name a few; with the focus of this dissertation on the dynamic changes in the ontogeny of MRP2 (an apical liver transport protein) and the dynamic changes caused by an immune response to a therapeutic monoclonal antibody (mAb). Several approaches can be used to …

Skrining Dan Evaluasi Aktivitas Kitinase Dari Sembilan Isolat Bakteri Lokal, Baitha Palanggatan Maggadani, Siswa Setyahadi S, Harmita Harmita

Pharmaceutical Sciences and Research

Chitinase is an enzyme that degrades chitin on β-1,4-acetamido-2-deoxy-D-glycoside bound to produce Chitin oligosaccharide or its soluble monomer, N-acetylglucosamine (NAG). Chitinase are usually produced naturally by chitinolytic microorganism that are found in soil or water environment. Chitinase have been widely used for biocontrol agents of plant pests. The product from chitinase hydrolysis can be used as antiinflammatory agent and anti hyperpigmentation. This research was aimed to screen and evaluate the chitinolytic ability of 9 isolate. The best isolate was the one which produced high chitinolytic activity and hydrolyzed chitin into NAG. 9 isolate were examined and BPPTCC-2 was the best …

Hubungan Kesesuaian Penulisan Resep Dengan Formulariumnasional Terhadap Mutu Pelayanan Pada Pasien Jaminankesehatan Nasional Di Rumah Sakit Umum Di Bandung, Winda Ratna Pratiwi, Angga Prawira Kautsar, Dolih Gozali

Pharmaceutical Sciences and Research

Pharmaceutical service is one of the activities in hospital that support health service quality. One of the factors that can improve quality of pharmaceutical services is prescription services. In the era of National Health Insurance, prescription given to the patients should be based on the National Formulary. If prescriptions did not suit the national formulary, it would influence the services quality on pharmacy unit. The purposes of this study were to determine suitability of prescription outpatients’ national health insurance with national formulary and to determine the relationship of the suitability of prescription with a national formulary to service quality in …

Kompleks Polielektrolit Kitosan-Xanthan Sebagai Matriks Sediaan Mukoadhesif, Kurnia Sari Setio Putri, Bambang Sulistomo, Silvia Surini

Pharmaceutical Sciences and Research

Mucoadhesive dosage form is a pharmaceutical dosage form with prolonged gastric residence time which can increase bioavailability of drugs. An excipient with suitable swelling and bioadhesive characteristics plays important role to obtain good mucoadhesive dosage form. Our pre-eliminary study showed that chitosan-xanthan gum polyelectrolyte complex (CXPC) in ratio 1:1 exhibit suitable swelling index to be developed as mucoadhesive dosage forms. This research was performed to study CXPC characteristics as matrix for mucoadhesive granules dosage form matrix. In this study CXPC 1:1 was utilized as the matrix in the mucoadhesive granules with drug-CXPC ratio of 1:1, 1:2, and 1:3, using diltiazem …

Perbandingan Efektifitas Antara Minyak Atsiri Kulit Batang Kayu Manis (Cinnamomum Burmannii) Dengan Temephos Sebagai Larvasida Aedes Aegypti, Muhamad Rizki Al Kamal, Neneng Syarifah Syafei, Gita Tiara Dewi Nasution

Pharmaceutical Sciences and Research

Dengue fever is a major health issue in the world. Preventive measure with temephos/abate has long been used to combat this problem. Istiana et al reported that there were cases of resistance of Aedes aegypti larvae to temephos in various parts of the world, including Indonesia. Indonesian Cinnamon (Cinnamomum burmannii) has been proven to possess larvacide effect and can be used as an alternative insecticide. This research was meant to compare the larvacide effect of Indonesian cinnamon (Cinnamomum burmannii) essential oil to the larvacide effect of temephos against Aedes aegypti larvae. This research used laboratory experimental design analysis. The total …

Parameter Fisikokimia Dan Analisis Kadar Allyl Disulfidedalam Ekstrak Etanol 70% Bawang Putih (Allium Sativum L.)Dengan Perbandingan Daerah Tempat Tumbuh Parameter, Rini Prastiwi, Siska Siska, Nila Marlita

Pharmaceutical Sciences and Research

Garlic (Allium sativum L.) is one of the medicinal plants that has a potential to be developed to become a traditional medicine. Traditional medicinal products and medicinal plants which have good quality are determined by the quality and safety of the extract. One of many factors that can affect the quality is the growing area. This research aimed to compare the value of physicochemical parameters as well as the levels of compounds responsible for pharmacological activity in ethanol 70% extract of garlic obtained from two growing areas, Bogor and Wonosobo. The test results obtained from garlic extract of Bogor were: …

Pharmacodynamic Activity Of Fosfomycin Simulating Urinary Concentrations Achieved After A Single 3 Gram Oral Dose Versus Escherichia Coli Using An In Vitro Model, George G. Zhanel, Kate Parkinson, Sean Higgins, Andrew Denisuik, Heather Adam, Johann Pitout, Ayman Noreddin, James A. Karlowsky

Pharmacy Faculty Articles and Research

We assessed the activity of fosfomycin simulating urinary concentrations achieved after a single 3 gram oral dose against Escherichia coli using an in vitro pharmacodynamic model. Eleven urinary isolates of E. coli were studied. Isolates were ESBL-producing or carbapenemase-producing. The in vitro pharmacodynamic model was inoculated with an inoculum of (~1 × 10⁶ cfu/mL). Fosfomycin was administered to simulate maximum free (ƒ) urine (U) concentrations and a t_1/2 obtained after a standard single 3 gram oral dose in healthy volunteers (ƒU_max, 4000 mg/L; t_1/2, 6 h). Sampling was performed over 48 h to assess …

Neurofeedback Or Neuroplacebo?, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

This scientific commentary refers to ‘Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia’, by Schabus et al.. (doi:10.1093/brain/awx011).

Novel Experimental Method For The Determination Of The Minimum Agitation Speed For Solids Suspension In Flat-Bottomed Stirred Tank Reactors, Shriarjun Shastry

Theses

Knowledge of the minimum agitation speed, Njs, required to suspend finely divided solids in vessels stirred by an impeller is a critical parameter to properly operate industrial tanks in a large number of industrial operations. The most common experimental approach to measure N_js is that of Zwietering’s (Chem. Eng. Sci., 1958, 8, 244-253), consisting of visually inspecting the tank bottom and visually determining the impeller agitation speed at which the solids are observed to rest on the tank bottom for no more than 1-2 seconds before being swept away. This method is quite reliable, but a method …

Ethical Imperatives Of Timely Access To Orphan Drugs: Is Possible To Reconcile Economic Incentives And Patients’ Health Needs?, Rosa Rodriguez-Monguio, T. Spargo, Enrique Seoane-Vazquez

Pharmacy Faculty Articles and Research

Background

More than 6,800 rare diseases and conditions have been identified in the US, which affect 25–30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs.

Methods

Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of …

Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy

Theses, Dissertations and Capstones

Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

Benzylideneoxymorphone: A New Lead For Development Of Bifunctional Mu/Delta Opioid Receptor Ligands, Jason R. Healy, Padmavani Bezawada, Nicholas W. Griggs, Andrea L. Devereaux, Rae Reiko Matsumoto, John R. Traynor, Christopher W. Cunningham

Faculty Publications & Research of the TUC College of Pharmacy

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.

Cyclodextrin As A Drug Carrier Increasing Drug Solubility, Malka Silberberg

The Science Journal of the Lander College of Arts and Sciences

The development of a new drug requires research and evaluation before the drug is approved to enter the market. One of the factors determining the efficacy of a drug is the aqueous solubility of the drug. A current problem in today’s pharmaceutical industry is the low aqueous solubility of many useful drugs. A drug with a low aqueous solubility will not readily be absorbed by the body. The low aqueous solubility of a drug is often due to the drug’s hydrophobic character. Drug enhancement methods are necessary to avoid the obstacle of drug insolubility and many methods have been developed. …

Effects Of Core And Shell Modification To Tethered Nanoassemblies On Sirna Therapy, Steven Rheiner

Theses and Dissertations--Pharmacy

siRNA therapy is an emerging technique that reduces protein expression in cells by degrading their mRNAs via the RNA interference pathway (RNAi). Diseases such as cancer often proliferate due to increased protein expression and siRNA therapy offers a new method of treatment for those diseases. Although siRNA therapy has shown success in vitro, it often fails in vivo due to instability in the blood stream. To overcome this limitation, delivery vehicles are necessary for successful transfection of siRNA into target cells and cationic polymers have been widely studied for this purpose. However, complexes between siRNA and delivery vehicles made …

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical …

Halo- And Solvato-Fluorochromic Polymer Nanoassemblies For Cancer Theranostics, Derek Alexander Reichel

Theses and Dissertations--Pharmacy

Theranostics is an emerging treatment approach that combines diagnostics with therapy in order to personalize treatment regimens for individual patients and decrease cancer mortality. Previously, nanoparticles entrapping conventional fluorescent dyes were developed for cancer theranostics, but fluorescent nanoparticles did not allow clinicians to significantly improve cancer treatments.

The use of fluorescent dyes that are sensitive to solvent acidity (halo-fluorochromism) and polarity (solvato-fluorochromism) may overcome the limitations of fluorescent nanoparticles and improve cancer therapy by enabling researchers to detect chemical properties within the nanoparticle core environment. The model halo- and solvato-fluorochromic dye Nile blue was attached to the core of nanoscale …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Inhibition Of Oxidative And Conjugative Metabolism Of Buprenorphine Using Generally Recognized As Safe (Gras) Compounds Or Components Of Dietary Supplements, Neha V. Maharao

Theses and Dissertations

This dissertation aimed at developing an inhibitor strategy to improve the oral bioavailability (F_oral) and systemic exposure (AUC_∞) of buprenorphine (BUP) as well as reduce the variability associated with them. Twenty-seven generally recognized as safe (GRAS) compounds or dietary substances were evaluated for their potential to inhibit the oxidative and conjugative metabolism of BUP, using pooled human intestinal and liver microsomes. In both the organs, oxidation appeared to be the major metabolic pathway with a 6 fold (intestine) and 4 fold (liver) higher intrinsic clearance than glucuronidation. Buprenorphine was predicted to show low and variable F …

Evaluation Of The Regional Drug Deposition Of Nasal Delivery Devices Using In Vitro Realistic Nasal Models, Mandana Azimi

Theses and Dissertations

The overall objectives of this research project were i) to develop and evaluate methods of characterizing nasal spray products using realistic nasal airway models as more clinically relevant in vitro tools and ii) to develop and evaluate a novel high-efficiency antibiotic nanoparticle dry powder formulation and delivery device. Two physically realistic nasal airway models were used to assess the effects of patient-use experimental conditions, nasal airway geometry and formulation / device properties on the delivery efficiency of nasal spray products. There was a large variability in drug delivery to the middle passages ranging from 17 – 57 % and 47 …

Investigation Of Polymeric Composites For Controlled Drug Release, Hsi-Wei Yeh

Theses and Dissertations

The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of …

A Biorelevant In Vitro Model To Characterize In Vivo Release Of Bone Morphogenetic Protein-2 (Rhbmp-2), Deblina Biswas

Theses and Dissertations

Biorelevant in vitro release/dissolution tests are designed to predict the in vivo behavior of a drug and are crucial in understanding its in vivo performance. Currently, there is no standardized compendial in vitro release testing methods or regulatory guidance’s for release/dissolution testing of implants due to their complex physiological locations.Furthermore, existing compendial methods do not capture the local release profile of ‘novel’ parenterals in physiological low fluid volume surrounding areas.

Long acting and in situ forming implants with orthobiologic proteins and peptides have increased over the past few decades due to a better understanding of genetic engineering. One of these …

Lung Disposition Model-Based Analyses Of Clinical Pharmacokinetic Profiles For Inhaled Drugs, Anuja Raut

Theses and Dissertations

There has been a desire to accurately interpret the inhaled pharmacokinetic (PK) profiles of drugs in humans to aid successful inhaled drug and product developments. However, challenges are layered, as 1) the drug dose delivered to the lung (DTL) from inhalers is a portion of the formulated dose but rarely determined; 2) lung delivery and regional deposition differ, depending on drug, formulation and inhaler; 3) drugs are not only absorbed from the lung but may also be from the gastrointestinal (GI) tract; and 4) in addition to absorption into the systemic circulation, multiple non-absorptive processes also eliminate drugs from the …

Pharmaceutical M&A Activity: Effects On Prices, Innovation, And Competition, Barak D. Richman, Will Mitchell, Elena Vidal, Kevin Schulman

Faculty Scholarship

The rise of blockbuster pharmaceutical acquisitions has prompted fears that unprecedented market concentration will weaken competition. Two of the most prominent concerns focus on the upstream and downstream ends of the pharmaceutical industry: (1) the concern that these mergers will concentrate the market for discovery and will therefore lead to fewer discoveries; and (2) the concern that merging large marketing, sales, and distribution forces will strengthen the hands of select pharmaceutical manufacturers and weaken downstream competition. Having considered potential dynamic effects in the industry and conducted a series of preliminary interviews with knowledgeable observers, though, this Article argues that neither …

Engineered Peptides For Applications In Cancer-Targeted Drug Delivery And Tumor Detection, R. Soudy, N. Byeon, Y. Raghuwanshi, S. Ahmed, A. Lavasanifar, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting …