Pharmaceutics and Drug Design Commons^™

A New Method For Investigating Bioequivalence Of Inhaled Formulations: A Pilot Study On Salbutamol, Homa Razaei, Maryam Khoubnasabjafari, Vahid Jouyban-Gharamaleki, Hamed Hamishehkar, Mohammad Reza Afshar Mogaddam, Elaheh Rahimpour, Reza Mehvar, Abolghasem Jouyban

Pharmacy Faculty Articles and Research

Purpose: An efficient, cost-effective and non-invasive test is required to overcome the challenges faced in the process of bioequivalence (BE) studies of various orally inhaled drug formulations. Two different types of pressurized meter dose inhalers (MDI-1 and MDI-2) were used in this study to test the practical applicability of a previously proposed hypothesis on the BE of inhaled salbutamol formulations.

Methods: Salbutamol concentration profiles of the exhaled breath condensate (EBC) samples collected from volunteers receiving two inhaled formulations were compared employing BE criteria. In addition, the aerodynamic particle size distribution of the inhalers was determined by employing next generation impactor. …

Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali

Pharmaceutical Sciences (PhD) Dissertations

The Ca²⁺-activated potassium channels K_Ca channels are a unique family of potassium channels activated by intracellular calcium. K_Ca channels are critical for maintaining K⁺ homeostasis and modulate several physiological processes, from the firing properties of neurons to the control of the transmitter release. The Ca²⁺ sensitivity of these channels allows intracellular Ca²⁺ to regulate the electrical activity of the cell membrane. Increased Ca²⁺ sensitivity of K_Ca channels caused by gain of function mutations (GOF) in the KCNN genes results in a broad spectrum of human channelopathies, including Zimmermann- Laband syndrome (ZLS), …

Solid Dispersion Technology For Improving The Solubility Of Antiviral Drugs, Maria Elvina Tresia Butar-Butar, Nasrul Wathoni, Hestiary Ratih, Yoga Windhu Wardhana

Pharmaceutical Sciences and Research

Most drugs, including antiviral drugs, show low solubility in water, which affects dissolution, bioavailability, and therapeutic effectiveness. Therefore, many antiviral drugs are given in very large doses. One of the efforts to overcome these problems is the application of solid dispersions in which polymers and surfactants can trap drug molecules that are in the amorphous phase. Drugs in a hydrophilic carrier will increase wettability, water absorption capacity, and porosity of particles, so that the drug is released better. This review article will discuss the development of technology in solid-state, how solid dispersion overcomes the lack of solubility and the rate …

Synthesis Of Ferrous Fumarate From Indonesian Iron Sand And In Vivo Body Weight Gain Test In Rats, Taufiq Indra Rukmana, Felicia Natalia Kurniadi, Harmita Harmita

Pharmaceutical Sciences and Research

Iron deficiency anemia (IDA) is a health problem in Indonesia. Prevention and treatment of IDA is carried out by giving fortified foods and oral iron therapy. Both can use ferrous fumarate which is made with reacting bivalent iron and disodium fumarate. Bivalent iron can be obtained from iron sand in Indonesia. This study aims to synthesize ferrous fumarate from Indonesian iron sand, which is from Malang, Sukabumi, and Cianjur area, and to determine its absorption through in vivo body weight gain test in male Wistar white rats (Rattus norvegicus). First, ferrous fumarate was synthesized through reaction of ferrous …

Beyond Use Date (Bud) Determination Of Ambroxol Hydrochloride Syrup By High-Performance Liquid Chromatography – Uv/Vis Detector, Catur Jatmika, Raditya Iswandana, Indah Dewi Lestari

Pharmaceutical Sciences and Research

Ambroxol HCl is a mucolytic agent often used to treat respiratory disorders associated with excess mucus secretion. This study aims to determine the beyond-use date (BUD) of ambroxol HCl syrup on the market based on analysis of the decrease in drug content using High-Performance Liquid Chromatography (HPLC) – UV/Vis detector. The HPLC conditions were reversed-phase with a C18 column, mobile phase containing acetonitrile - phosphate buffer 0.05 M pH 4.5 (60:40) at a flow rate of 1.0 ml/min using UV detection at 248 nm. To determine BUD, five syrup preparations (brands) obtained from the Jakarta area were analyzed in triplicate. …

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …

The Application Of Continuous Stationary Phase Gradients To High-Performance Liquid Chromatography And Its Potential To Improve Pharmacological Research, Hannah Klose

Senior Honors Theses

The separation of mixtures into different components is integral to experimentation and analysis in a multitude of fields. Chromatography is one of the most popular, well-developed, and well-studied methods used to examine the makeup of a mixture. Thus, the improvement of chromatographic procedures directly benefits research across many scientific disciplines. The application of a continuous stationary phase gradient to High-Performance Liquid Chromatography (HPLC) methods has been proposed to improve the separation of complex mixtures that are difficult to achieve with existing separation techniques. By incorporating a gradient stationary phase, analysts will create a more selective mode of separation to improve …

Development, Optimization, And In Vitro/In Vivo Evaluation Of Azelaic Acid Transethosomal Gel For Antidermatophyte Activity, Ali Nasr, Noha Badawi, Yasmine Tartor, Nader Sobhy, Ali Nasr

Pharmacy

Treatment of dermatophytosis is quite challenging. This work aims to investigate the antidermatophyte action of Azelaic acid (AzA) and evaluate its efficacy upon entrapment into transethosomes (TEs) and incorporation into a gel to enhance its application. Optimization of formulation variables of TEs was carried out after preparation using the thin film hydration technique. The antidermatophyte activity of AzA-TEs was first evaluated in vitro. In addition, two guinea pig infection models with Trichophyton (T.) mentagrophytes and Microsporum (M.) canis were established for the in vivo assessment. The optimized formula showed a mean particle size of 219.8 ± 4.7 nm and a …

Computational Evaluation Of Bioactive Compounds From Vaccinium Vitis-Idaea L (Ligonberry) For Treating Kras-Associated Lung Cancer, Ayooluwa Ilesanmi, Gbenga Dairo, Toheeb Balogun, Bibiire Awoyale

Undergraduate Research Conference

Lung cancer is the cancer of the lung's epithelial cells typically characterized by difficult breathing, chest pain, blood-stained coughs, headache, and weight loss. If left unmanaged, lung cancer can spread to other body parts. While several treatment methods exist for managing lung cancer, exploring natural plant sources for developing therapeutics offers great potential in complementing different treatment approaches. In this study, we concentrated on inhibiting the mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) by targeting an associated protein (Phosphodiesterase 6δ) to which KRAS form complexes. We evaluated bioactive compounds from Lingonberry (Vaccinium vitis-idaea L), adopting computational approaches such as …

Virtual And In Vitro Screening Of Natural Products Identifies Indole And Benzene Derivatives As Inhibitors Of Sars-Cov-2 Main Protease (MPro), Dony Ang, Riley Kendall, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with …

Effectiveness And Safety Of Apixaban Vs Warfarin In Patients With Venous Thromboembolism With Risk Factors For Bleeding Or For Recurrences, Alexander T. Cohen, Janvi Sah, Amol D. Dhamane, Dionne M. Hines, Theodore Lee, Lisa Rosenblatt, Birol Emir, Allison Keshishian, Huseyin Yuce, Xuemei Luo

Publications and Research

Introduction

Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences.

Methods

Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia …

The Science Of Oral Carbapenems, Landon Olsen, Daniel J. Yang, Aiyi Chen, Thahn-Liem Vu, H. Stephen Lee

Annual Research Symposium

No abstract provided.

A Ligand-Based Approach To Identifying Commercially Available Inhibitors Of Human Galactokinase (Galk), Tyler Rose

Annual Research Symposium

The purpose of this project was to find inhibitors of the human galactokinase (GALK) enzyme. GALK is responsible for catalyzing the conversion of galactose to galactose 1-phosphate, the first step in galactose metabolism. Galactose 1-phosphate builds up in the cells of patients with type 1 galactosemia due a genetic disorder. It has been proposed that inhibiting galactose 1-phosphate production by GALK may prevent many of the major complications of type 1 galactosemia. In this study, a ligand-based approach was used to identify commercially available inhibitors of GALK, starting from galactose-bearing natural products. Candidate inhibitors were screened for their ability to …

Tech Note 2023-1 Nih Contribution To Phased Clinical Development Of Drugs Approved From 2010-2019, Edward Zhou, Matthew Jackson, Fred Ledley

CISI Publication

This report describes the methods and preliminary results for the manuscript titled, “Spending on Phased Clinical Development of Approved Drugs by the US National Institutes of Health Compared With Industry.”

Characterization, Antibacterial, Antioxidant, Antidiabetic, And Anti-Inflammatory Activities Of Green Synthesized Silver Nanoparticles Using Phragmanthera Austroarabica A. G. Mill And J. A. Nyberg Extract, Shady Swidan, Dina Khodeer, Sarah Shabayek, Ali Nasr, Roaa Khinkar, Mohammed Aldurdunji, Maryam Ramadan, Jihan Badr

Pharmacy

Introduction: Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.

Methods: The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.

Results …

Pharmacology Of Disulfiram As An Antibacterial Agent, Yogesh Meka

Theses, Dissertations and Capstones

Disulfiram (Antabuse®) is an oral prescription drug used to treat alcohol abuse disorder (AUD). Disulfiram (DSF) and its metabolites act on the body by inhibiting multiple enzymes involved in alcohol metabolism. This study aims to understand the pharmacology of disulfiram as an antibacterial medication. Previous studies on DSF showed antibiotic activity against multidrug-resistant Staphylococcus aureus strains (MRSA). The initial aim of this study was to decipher the mechanisms involved in inhibiting bacterial growth by DSF, which was done by performing biochemical studies. The studies revealed that DSF had antagonistic effects on redox buffering and energy production. Another aim of this …

Investigating The Use Of Mpges-1 Inhibitors For The Treatment Of Abdominal Aortic Aneurysms, Lauren M. Weaver

Theses and Dissertations--Pharmacy

The cardiovascular field is still searching for a treatment for abdominal aortic aneurysms (AAA). This inflammatory disease is a deadly, permanent ballooning of the aortic artery. It often goes undiagnosed until a late stage where associated rupture has a high mortality rate. Surgery is the only option available to patients, but it is risky. There are currently no FDA-approved pharmacological treatments for AAA available. Historically, drugs that have been examined in interventional clinical trials for treatment of AAA were repurposed therapeutics. Novel treatments have been unable to reach the clinic, stalling out in pre-clinical studies. Exceedingly few murine studies have …

Effectiveness Of A Long-Acting Cocaine Hydrolase In Metabolizing Cocaine And Its Physiologically Active Metabolites, Linyue Shang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy specific for cocaine addiction or overdose. Cocaine-induced toxicity in animals and humans is due to its multiple physiological effects on the central nervous system, cardiovascular system, etc. The toxicity of cocaine is highly complex, as its metabolites also contribute to the toxicity. Notably, the combination of cocaine and alcohol is common among drug users and can produce additional metabolites. Some of the metabolites are more toxic than cocaine itself. Hence, to develop an ideal therapeutic candidate, the candidate should not only account for cocaine but should also detoxify other …

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic

Theses and Dissertations--Pharmacy

Ubiquitin (UB) and ubiquitin-like protein (UBL) pathways have emerged as important targets for oncology drug discovery based on the success of proteasome inhibitors (bortezomib or carfilzomib), E3 inhibitors, and the NEDD8 E1 inhibitor pevonedistat (MLN42924). Chemical inhibitors have also proven to be useful probes for identifying and dissecting multifactor UB and UBL regulatory networks. Toward this end, we have pursued approaches to target NEDD8 ligation to Cullins, through developing small molecule inhibitors of DCN1 (defective in Cullin Neddylation 1). DCN1 was discovered as a potentiating RBX1-dependent NEDD8-ligation, through recognizing the acetylated N-terminal methionine of the NEDD8 E2s UBE2M and UBE2F. …