Pharmacy and Pharmaceutical Sciences Commons^™

Fabrication Of Topical Film Forming Polymeric Solution For Pain Management, Maha Hani Alkurdi

Electronic Theses and Dissertations

FFS were developed by varying the type and content of the film forming polymer. The resulting formulations were evaluated according to favorable film characteristics in vitro and ex vivo drug release profiles. Eudragit E100 was identified as a suitable release matrix for ketoprofen. In the case of diclofenac Na; however the ex vivo permeation study results failed to show a characteristic release profile for either the test formulation or the marketed formulation VOLTAREN® Gel. Nevertheless the presented work provided a rationalized way for the development and evaluation of FFS and investigated their potential as delivery systems for ketoprofen and diclofenac …

In-Situ Gel Of Cyclosporine A – Loaded Solid Lipid Nanoparticles For Topical Occular Delivery For Dry Eye Disease, Samir Shyambabu Senapati

Electronic Theses and Dissertations

Cyclosporine (CSA) is a highly potent immunosuppressant drug and has been used to treat rheumatoid arthritis, psoriasis, organ rejection post-transplant, and chronic dry eye disease. The objective of this investigation was to increase the CSA residence time on the ocular surface using solid lipid nanoparticles (SLNs) and its in-situ gel formulation (CSA-SLN-IG), for treatment of dry eye disease. CSA loaded SLNs (CSA-SLN) were prepared with the homogenization method, using Precirol ® ATO 5 as a solid lipid and Tween® 80 and Poloxamer 188 as surfactants. Prepared SLNs were optimized based on particle size, zeta potential (ZP), PDI, assay and stability. …

Globalization Of Clinical Research And Assessment Of Global Access To Treatments Approved Between 2006-2015, Rafael Duncan Escandon

Walden Dissertations and Doctoral Studies

Globalization in clinical research and development has increased since the 1990s. Products approved in the United States (U.S.) and European Union (EU) include increasing numbers of research participants from low- and middle-income countries. The purposes of this quantitative correlational study were to investigate the lag time, or drug lag, between U.S. approval and the approval of selected drugs in all countries that hosted their pivotal clinical trials. The study population was limited to products approved first in the U.S. between 2006 and 2015. The health capability model and research for health justice framework were the theoretical frameworks for the study. …

The Orphan Drug Act At 35: Observations And An Outlook For The Twenty-First Century, Nicholas Bagley, Benjamin Berger, Amitabh Chandra, Craig Garthwaite

Articles

On the thirty-fifth anniversary of the adoption of the Orphan Drug Act (ODA), we describe the enormous changes in the markets for therapies for rare diseases that have emerged over recent decades. The most prominent example is the fact that the profit-maximizing price of new orphan drugs appears to be greater today than it was in 1983. All else equal, this should reduce the threshold for research and development (R&D) investment in an economically viable product. Further, the small size of patient populations for orphan drugs, together with the increasing prevalence of biologics among orphan drugs, have created a set …

Regulatory Gaps In Drug Compounding: Implications For Patient Safety, Innovation, And Fraud, Joanna Shepherd

Faculty Articles

Drug compounding is the practice of mixing, combining, or altering drug ingredients to create a product that meets the medical needs of a patient whose needs cannot otherwise be met with commercially-available products. Compounding is essential for patients that are allergic to certain ingredients or cannot tolerate the route of administration or dosage form of a commercially-available drug. Compounding may also enable pharmacists to supply medications when there is a shortage of commercially-available drugs. For example, amid the nationwide shortage of generic liquid Tamiflu and growing flu deaths in early 2018, pharmacists around the country used Tamiflu capsules to compound …

การประเมินผลการใช้เครื่องมือวัดคุณภาพชีวิตด้านการรักษาด้วยยาร่วมกับการบริบาลทางเภสัชกรรมสำหรับผู้ป่วยนอก, อชิรญา บุตรดาน้อย

Chulalongkorn University Theses and Dissertations (Chula ETD)

วัตถุประสงค์: ประเมินผลของการใช้แบบสอบถาม PROMPT ในการให้บริบาลทางเภสัชกรรม ในด้านการสื่อสารเรื่องคุณภาพชีวิตด้านการใช้ยาระหว่างเภสัชกรและผู้ป่วย การค้นหาปัญหาจากการใช้ยา การติดตามผลการแก้ไขปัญหาจากการใช้ยา ความร่วมมือในการใช้ยา การเปลี่ยนแปลงแนวทางการรักษาผู้ป่วยของแพทย์ และคุณภาพชีวิตด้านการใช้ยา วิธีการวิจัย: การทดลองแบบสุ่มที่มีกลุ่มควบคุม ในผู้ป่วยนอกจำนวน 315 คน ที่เข้ารับการรักษาที่โรงพยาบาลสมุทรปราการระหว่างเดือนสิงหาคม 2561 ถึง กุมภาพันธ์ 2562 แบ่งผู้ป่วยเป็น 2 กลุ่มคือ กลุ่มมาตรฐาน (กลุ่มที่ไม่ใช้แบบสอบถาม PROMPT ในการบริบาลทางเภสัชกรรม) และกลุ่มศึกษา (กลุ่มที่ใช้แบบสอบถาม PROMPT ในการบริบาลทางเภสัชกรรม) โดยมีการเก็บข้อมูลจำนวน 2 ครั้ง คือ ก่อนการแทรกแซกและหลังการแทรกแซงเมื่อผู้ป่วยมาพบแพทย์ในครั้งถัดไป ผลการวิจัย: คะแนนการสื่อสารของผู้ป่วยทั้ง 2 กลุ่ม มีความแตกต่างกันอย่างมีนัยสำคัญทางสถิติ (p < 0.001) กลุ่มศึกษาพบปัญหาจากการใช้ยามากกว่ากลุ่มมาตรฐาน (p<0.05) และมีคะแนน คุณภาพชีวิตด้านการใช้ยาดีขึ้นอย่างมีนัยส าคัญทางสถิติเมื่อเทียบกับกลุ่มมาตรฐาน (p<0.01) สรุปผลการวิจัย: การให้บริบาลทางเภสัชกรรมโดยใช้แบบสอบถาม PROMPT ช่วยเพิ่มการ สื่อสารเรื่องคุณภาพชีวิตการใช้ยาระหว่างผู้ป่วยกับเภสัชกร และช่วยให้คุณภาพชิวิตด้านการใช้ยาของ ผู้ป่วยดีขึ้นได้

Application Of Near-Infrared Spectroscopic Technique In Content Uniformity Monitoring Of 5 Mg Amlodipine Tablets During Compression, Nattaporn Poltem

Chulalongkorn University Theses and Dissertations (Chula ETD)

Near-Infrared Spectroscopy (NIRs) technique was used to quantitatively analyzed 5 mg amlodipine tablets. The aim of this study was to develop calibration model by NIRs technique to accurately determine content uniformity of amlodipine tablets during commercial scale production. Amlodipine tablets were initially manufactured in laboratory scale to generate calibration model with concentrations ranging from 80% to 120% labeled amount using NIRs analysis with spectral range of 4000 –10000 cm-1. Results were compared with reference High-Performance Liquid Chromatographic (HPLC) method. Best near-infrared spectral preprocessing were obtained by utilizing Savitzgy-Golay 1st Derivative treatment followed by Standard Normal Variate (SNV) to improve data …

Formulation Development, Preclinical Testing, And Primary Packaging Optimization For Cannabinoids And Other Therapeutics, Pranjal Taskar

Electronic Theses and Dissertations

Through the process of drug development, a molecule goes through discovery screening; lead selection and optimization, ADME testing, toxicity profiling, dosage form determination, preclinical testing in an in vitro and in vivo setup, folloby clinical research, FDA review and approval until eventually it is manufactured in the determined dosage form and reaches the patient. At every point through this process, scientists actively work towards a smoother transition and a quick and safe approval of the molecule towards the next step. The different chapters in this research would cover various phases of drug development; from discovery stage to fill-finish and primary …

Rhabdomyolysis Associations With Antibiotics: A Pharmacovigilance Study Of The Fda Adverse Event Reporting System (Faers), Chengwen Teng Pharm.D., Ph.D., Courtney Baus, James P. Wilson, Christopher R. Frei

Faculty Publications

Introduction: Daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir are known to be associated with rhabdomyolysis. Other antibiotics may also lead to rhabdomyolysis, but no study has systemically compared rhabdomyolysis associations for many available antibiotics.

Objectives: The objective of this study was to evaluate the association between rhabdomyolysis and many available antibiotics using the FDA Adverse Event Report System (FAERS).

Methods: FAERS reports from January 1, 2004 to December 31, 2017 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify rhabdomyolysis cases. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the …

Synthesis Of A Novel Surface Active, Light Sensitive Polymer For Encapsulation And Delivery Of Paclitaxel, Amit Raviraj Pillai

Electronic Theses and Dissertations

Melanoma and non-melanoma (basal cell and squamous cell carcinoma) skin cancer (NMSC) have been recognized as an epidemic as they happen to be the most comtype of cancers in the white population. Cancer cell targeting i.e. differentiating cancer cells from normal cells has been an area of active research to reduce the side effects of cancer chemotherapy. For this research project, we have developed a novel light sensitive Methylene Blue (MB)-Polyethylene glycol (PEG) conjugate with significant surfactant properties. The aim of this study was to synthesize a smart light sensitive polymer which activates and releases the encapsulated drug on exposure …

Investigation Of Theophylline Nicotinamide Pharmaceutical Co-Crystals Utilizing Hot Melt Extrusion, Priyanka Srinivasan

Electronic Theses and Dissertations

The objective of the current study was to investigate the feasibility of Theophylline and Nicotinamide pharmaceutical co-crystals by hot melt extrusion technology and to evaluate the processability by using HPMCAS-MG and PEO as polymer carriers. Theophylline, a BCS class I was chosen as a model drug and Nicotinamide, a vitamin B family was selected as a suitable co-former for the co-crystals study. HPMCAS-MG, a synthetic polymer and PEO, water-soluble polymer were chosen as polymer carriers for the study. To optimize the process parameters and formulations, a physical mixture of 1:1 molar ratio of theophylline and nicotinamide were prepared. Physical mixture …

Application Of Quality By Design And Process Analytical Technology Towards Hot-Melt Extrusion Processes, Priyanka Thipsay

Electronic Theses and Dissertations

Solid self-emulsifying drug delivery systems were developed instead of a conventional liquid system. Solid surfactants was chosen to emulsify lipids with different HLB properties. Type of surfactant, type of lipid, Lipid/surfactant L/S ratio, feed rate, screw speed and screw configuration, were the formulation and process parameters evaluated. Solid self-emulsifying drug delivery systems were successfully developed on the hot-melt extruder for the first time which is a continuous processing technology.

Novel Application Of Melt Extrusion And Additive Manufacturing On Developing Diverse Dosages, Jiaxiang Zhang

Electronic Theses and Dissertations

New drug product development is a time consuming and costly process. One of the significant challenges is the poor aqueous solubility of many active pharmaceutical ingredients (APIs). Among those techniques, hot-melt extrusion(HME) is optimal for pharmaceutical solid dispersion development because of it free of using an organic solvent, easy scale up, and suitable for continuous processing with ensured optimal quality control.

Comparative Effectiveness And Safety Of Non-Vitamin K Antagonists Oral Anticoagulants And Warfarin In Elderly Patients With Non-Valvular Atrial Fibrillation And Diabetes, Siddhi Korgaonkar

Electronic Theses and Dissertations

Results: The matched sample consisted of 4578 patients (2291 in each group). NOACs were found to significantly reduce the risk of stroke/SE compared to warfarin (Hazard Ratio (HR): 0.373, 95% confidence interval (CI): 0.247 - 0.564, p<0.001); but, no significant difference was seen between NOACs and warfarin in terms of reducing the risk of MI (HR: 0.864, CI: 0.594 – 1.257, p=0.446). NOACs were found to significantly reduce the risk of ICH (HR: 0.500, CI: 0.300 – 0.834, p=0.008) and OB (HR: 0.608, CI: 0.424 – 0.870, p=0.007); but no difference was seen in the risk of MGB (HR: 0.862, CI: 0.640 – 1.160, p=0.326) between NOACs and warfarin. NOACs were also found to reduce the risk of all-cause mortality (HR: 0.783, CI:0.656 – 0.873, p=0.007). The composite of effectiveness and safety outcomes, and all-cause mortality was statistically significant proving superior overall effectiveness and safety of NOAC therapy to warfarin therapy in terms of risk reduction (HR:0.685, CI:0.587 – 0.801, p<0.001).

Valuation Of Mentorship In Pharmacy Education And The Impact Of Perceived Personal Relevance, Ashley Stubblefield Crumby

Electronic Theses and Dissertations

Mentorship is an important component of personal and professional development for student pharmacists. This research measured the value of mentorship in this population examined potential influencing factors and the likelihood to participate in a mentoring relationship and identified preferences for the mentoring relationship. Data collection involved survey self-report of student pharmacists (P1-P4) at four participating universities. An adapted 29-item Mentoring Functions Scale (MFS) was used to measure value with functions divided into career and psychosocial categories. The highest ranked mentoring functions were psychosocial with an average score of 9 or greater on the 10-point scale. Perceived personal relevance measured using …

Pharmacy Value-Based Incentive Programs: An Evaluation Of Health Plan Strategies, Pharmacist Attitudes, And Financial Impact On Retail Stores, Tristen H. Jackson

Electronic Theses and Dissertations

Since the Affordable Care Act (ACA) in 2012 health plans serving Medicare beneficiaries have begun receiving sizeable incentives (>$1B) for demonstrating high ratings to quality performance scores in CMS’s Medicare star ratings program. Several of the quality measures can be directly impacted by retail pharmacists (e.g. medication adherence measures) resulting in health plans implementing programs designed to incentive retail pharmacies to work toward improving their own performance related to quality measures. While awareness of these value-based incentive (VBI) programs is growing there is still a significant lack of research which elucidates the nature of these programs and the potential …

Comparative Assessment Of Safety And Quality Of Tinospora Species-Tinospora Crispa And Tinospora Sinensis, Abidah Parveen

Electronic Theses and Dissertations

Tinospora crispa Miers ex Hook.f. & Thomson and Tinospora sinensis (Lour.) Merr. (Menispermaceae) are two species that have morphological similarities which makes distinction between the two of critical importance because T. crispa has been reported to cause hepatotoxicity. Comparative morpho-anatomy of the leaves and stems of Tinospora species indigenous to south and southeast Asia was undertaken to elaborate their distinguishing pharmacognostic features. Chemical characterization of the secondary metabolites of the two species may aid in elucidating their chemical diversity and hence help to resolve safety and quality issues. Phytochemical investigation of the stems led to the isolation of nineteen compounds …

Role Of Cardiolipin Remodeling In The Malignant Progression Of Breast Cancer, Jawaher H. Alkhamisy

Electronic Theses and Dissertations

In spite of the current advances in both radiotherapy and surgical techniques as well as molecularly targeted therapies, over 90 percent of cancer mortality rate is due to metastases. Considering the pivotal role of metabolism in cellular physiology, there is no doubt that metabolic alterations are critical for metastatic progression. Cardiolipin (CL), the signature phospholipid of mitochondria, is linked to a variety of vital mitochondrial processes, like oxidative phosphorylation. Cardiolipin is a unique dimeric phospholipid which contains four fatty acyl chains. Moreover, the CL remodeling process is believed to be responsible for generation of immature CL species that contribute to …

Unraveling Anticancer Activity And Pharmacokinetics Of Dihydroartemisinin Dimer Oxime, Lu Dai

Electronic Theses and Dissertations

Artemisinin is currently used as an antimalaria drug. Studies have shown its monomeric form exhibited promising anticancer effects by inhibiting the proliferation, inducing apoptosis, and increasing oxidative stress of tumor cells. Recently, several dimeric forms of artemisinin have been synthesized with more potent anticancer activity. In this study, nine dihydroartemisinin dimers with diversely functionalized linkers exhibited similar cytotoxicity against human breast adenocarcinoma MDA-MB-231 in vitro. Among these nine DHA dimers, DHA dimer oxime was selected for further anticancer activity and pharmacokinetic study. Our preliminary study shothat DHA dimer oxime displayed more than a 10-fold increase of antiproliferation effect over its …

End Of Life Costs In Medicare Beneficiaries With Parkinson’S Disease, Sasikiran Nunna

Electronic Theses and Dissertations

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder which is characterized by motor and non-motor disorders. The prevalence of PD is high among elderly patients. Due to the chronic nature of PD, increasing prevalence and ageing population, it is important to understand the burden of PD at various stages of patient’s life so that value of PD therapies can be assessed. While direct healthcare costs during the life time of PD were assessed in previous studies, there is lack of information about end of life costs in PD patients. This dissertation aimed at filling the gap in literature …

Characterization Of Drug-Loaded Milled Extrudate Particles Produced By Hot Melt Extrusion Technology For Dry Powder Inhalers, Ahmed Almotairy

Electronic Theses and Dissertations

The aim of the current investigation is to develop a sustained-release dry powder inhalation (DPI) formulation through continuous Hot Melt Extrusion (HME) process and see the impact of Sodium Bicarbonate (SB) and Mannitol (MAN) on the hydrophobic Eudragit RL PO (ERLPO) polymer. Ball milling and air-jet milling were utilized to have powder with a particle size range that is required for inhalation. Air-jet milled formulations shopromising particle size results compared to ball milled formulations. All solid-state characterization studies revealed no change on Theophylline (TH) crystallinity or occurrence of drug-excipient interactions in physical mixtures and formulations. X2 formulation released TH constantly …

Progress Toward The Synthesis Of 3-Methoxyflavones As Potential Antioxidants, Neuroprotective Agents, And Trifluoromethylated 19f Nmr Probes, Reem Alkhodier

Electronic Theses and Dissertations

The total synthesis of polyhydroxylated flavones have proven to be challenging, due to the presence of more than one hydroxyl group. Direct cyclization was not successful in any of the attempts. However, by using a silyl protecting group, the cyclization was feasible. Other reactions like the Friedel-Crafts acylation and selective protection of phenols were also difficult.

Synthesis Of Fluoroflavones As Potential Neuroprotective Agents, Maali Alshammari

Electronic Theses and Dissertations

Flavones are polyphenol natural products that are known to have neuroprotective effects against many diseases caused by the formation of reactive species. Flavonoids are subgroup of flavones and they are believed to function as antioxidants. Specifically, they target free radicals and eliminate its harmful effect on the cell. Fluoroflavones were designed to improve the potency of the antioxidant activity and potentially be used as neuroprotective agents. A monofluorinated and trifluoromethylated flavone were synthesized by using commercially available fluorination reagents, N-fluorobenzenesulfonimide; and Togni’s or Umemoto's respectively. After the synthesis of the desired flavones and their monofluorinated and trifluoromethylated derivatives, biological testing …

Design Of Thermosensitive Hydrogel For Extended-Release Of Praziquantel, Sheng Feng

Electronic Theses and Dissertations

Parasitic diseases are a severe threat to people and animals. Praziquantel is the most comanti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications …

Development Of Controlled Release Oral Dosages By Density Gradient Modification Using 3d Printing Technologies, Zhiqing Hu

Electronic Theses and Dissertations

Over the years, three-dimensional (3D) printing has gradually become more comin people's lives. Due to its quick development, it has attracted the attention of researchers in the pharmaceutical industry. The main purpose of this project was to couple fused deposition modelling (FDM) 3D printing with hot melt extrusion (HME) technology to manufacture tablets with different drug release profiles and to solve dose issues related to an individual’s physiological differences and to enhance extended release properties. Ketoprofen was used as the model drug and different properties were added to the polymer to create a formulation suited to HME technology for the …

Conformational Studies Of Glucose Transporter 1 (Glut1) As An Anticancer Drug Target, Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong

Journal Articles: Pharmaceutical Sciences

Glucose transporter 1 (GLUT1) is a facilitative glucose transporter overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. GLUT1 works through conformational switching from an outward-open (OOP) to an inward-open (IOP) conformation passing through an occluded conformation. It is critical to determine which conformation is preferred by bound ligands because the success of structure-based drug design depends on the appropriate starting conformation of the target protein. To find out the most favorable GLUT 1 conformation for ligand binding, we ran systemic molecular docking studies for different conformations of GLUT1 using known …

Spontaneous Self-Assembly Of Amyloid Β (1–40) Into Dimers, Mohtadin Hashemi, Yuliang Zhang, Zhengjian Lv, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The self-assembly and fibrillation of amyloid β (Aβ) proteins is the neuropathological hallmark of Alzheimer's disease. However, the molecular mechanism of how disordered monomers assemble into aggregates remains largely unknown. In this work, we characterize the assembly of Aβ (1–40) monomers into dimers using long-time molecular dynamics simulations. Upon interaction, the monomers undergo conformational transitions, accompanied by change of the structure, leading to the formation of a stable dimer. The dimers are stabilized by interactions in the N-terminal region (residues 5–12), in the central hydrophobic region (residues 16–23), and in the C-terminal region (residues 30–40); with inter-peptide interactions focused around …

Actinomycin Familial Diversity Driven By Phenoxazinone-Core Reactivity, Matthew Richard Mcerlean

Theses and Dissertations--Pharmacy

Actinomycins are a class of compounds consisting of phenoxazinone-like core attached to two peptidolactone rings, denoted as α and β. A unique component of a few families—actinomycins G, Y, and Z—is a chlorinated β-ring threonine residue. Families G and Y also contained an actinomycin that possess a β-ring heterocycle (actinomycins G₅ and Y₅, respectively); prior to this work, no β-ring heterocycle-containing actinomycins were reported for the Z family. Unlike other actinomycin derivatives, Y₅’s cytotoxicity was abolished while still maintaining some antibacterial potency.

We constructed a model compound to probe the physical properties of the actinomycin …

Developing A Workflow To Evaluate Medications For Repurposing Using Health Claims Data: Application To Substance Use Disorders, Emily Ruth Hankosky

Theses and Dissertations--Pharmacy

Healthcare big data are a growing source of real-world data with which to identify and validate medications with repurposing potential. Previously, we developed a claims-based workflow to evaluate medications with potential to treat stimulant use disorders. In order to test the workflow, the framework was applied in the context of opioid use disorders (OUDs), for which there are medications with known efficacy. Using the Truven Marketscan Commercial Claims Database, a nested case-control analysis was conducted to determine the association between OUD medications (buprenorphine, naltrexone) and remission. Cases were defined as enrollees with a remission diagnosis and matched (1:4) to controls …

Phase Behavior Of Amorphous Solid Dispersions: Miscibility And Molecular Interactions, Kanika Sarpal

Theses and Dissertations--Pharmacy

Over the past few decades, amorphous solid dispersions (ASDs) have been of great interest to pharmaceutical scientists to address bioavailability issues associated with poorly water-soluble drugs. ASDs consist of an active pharmaceutical ingredient (API) that is typically dispersed in an inert polymeric matrix. Despite promising advantages, a major concern that has resulted in limited marketed formulations is the physical instability of these complex formulations. Physical instability is often manifested as phase heterogeneity, where the drug and carrier migrate and generate distinct phases, which can be a prelude to recrystallization. One important factor that dictates the physical stability of ASDs is …