Pharmacy and Pharmaceutical Sciences Commons^™

Functionality And Role Of Different Fatty Alcohols In Topical O/W Cream Formulation, Supriya Bhide

Electronic Theses and Dissertations

Fatty alcohols are excipients that are abundantly used in various pharmaceutical formulations. The objective of the present study was to evaluate the impact of incorporating different fatty alcohols on microstructural and formulation characteristics of topical o/w clotrimazole cream formulation. The formulations containing different fatty alcohols as Kolliwax® CSA 50 (CSA 50), Kolliwax® CSA 70 (CSA 70), Kolliwax® MA (MA), Kolliwax® CA (CA), Kolliwax® SA (SA) were prepared by selecting suitable RPM and homogenization time. The M.P. of API and fatty alcohols were determined using DSC technique. The prepared cream formulations were evaluated for their phase separation. The various tests like …

Polymer Based Delivery Of Doxycycline Hyclate For The Prevention Of Peri-Implant Mucositis Infection, Sagar Deepak Sawant

Electronic Theses and Dissertations

Peri-implant mucositis is a silent inflammatory condition that is destructive in nature affecting only the soft tissues in the vicinity of dental implants. The current line of treatment includes the use of systemic antibiotics, mechanical debridement using LASER decontamination, the use of mouthwash or oral rinsing with chlorhexidine, maintenance and improvement of oral hygiene, mechanical debridement with or without systemic antibiotic treatment, mechanical debridement with or without the use of local drug delivery systems. However, these treatments do not solve the problem of implant rejection as peri-mucositis progresses to per-implantitis which causes severe bone loss and ultimately leading to implant …

Novel Applications Of Hot-Melt Extrusion Technology, Ajinkya Moreshwar Bhagurkar

Electronic Theses and Dissertations

Hot-melt extrusion, an adaptable technology, has established its position in a wide spectrum of manufacturing operations like amorphous solid dispersions, immediate and controlled oral formulations, implants, and taste masked products. In recent years the industrial focus has shifted towards continuous manufacturing, thus melt extrusion is being explored for new applications. The aim of this research work was to investigate the novel applications of hot-melt extrusion by carrying out an in depth study to understand the interplay between the process and the product. The conventional techniques used for the preparation of ointments and nanostructured lipid carriers are multi-step and time consuming …

Development And Characterization Of Fluocinolone Acetonide Loaded Nanosized Lipid Carriers For Ocular Delivery Via Subconjunctival Route: Synergistic Effect Of Vitamin A Palmitate, Bhavik Soneta

Electronic Theses and Dissertations

Though nanotechnology which exploits the use of nanoparticles for therapeutic application have embarked as an emerging tool for drug delivery applications, the delivery of therapeutic molecules into deep ocular compartments has always been a challenging task. In this regard, the main objective of our current investigation was to develop and evaluate the fluocinolone acetonide (FA) loaded nanostructure lipid carrier (FA-NLC) in situ gel for improved ocular bioavailability by subconjunctival injection. FA, a corticosteroid administered for inhibiting the ocular inflammation either as intravitreal injection or as intravitreal implants. The FA-NLCs were developed by using vitamin A palmitate as one of the …

Feasibility Of Aquasolvetm Hpmc-As Lg Via Hot-Melt Extrusion: Effect Of Pressurized Co2 On Physico-Mechanical Properties, Mashan Almutairi

Electronic Theses and Dissertations

The objective of the current study was to investigate the processability of Aquasolve™ HPMC-AS LG via hot-melt extrusion, and to examine the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of Efavirenz (EFA)-loaded extrudates (EXT). EFA is as a poorly water-soluble drug and HPMC-AS LG was chosen as a carrier for this study. To optimize the process parameters and formulations, various physical mixtures were prepared with the following composition: EFA (30-40-50% w/w) and HPMC-AS LG (70-60-50 % w/w) respectively. Physical mixtures were extruded through the co-rotating twin-screw extruder (16mm Prism Euro Lab, Thermo Fisher Scientific) utilizing a standard …

Synthesis And Characterization Of Redox-Sensitive Polymer And Prodrug For Targeted Drug Delivery, Chang-Hee Whang

Electronic Theses and Dissertations

Systemic administration of chemotherapeutics is associated with various side effects deriving from accumulation in off-target sites and acute toxicity of the drugs. In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy. This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms. By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer …

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 …

Preparation And Evaluation Of Cefuroxime Axetil Gastro-Retentive Floating Drug Delivery System For Improved Delivery Via Hot-Melt Extrusion Technology, Rahul Madhukar Lalge

Electronic Theses and Dissertations

Purpose: The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery system of amorphous Cefuroxime Axetil (CA) to minimize the enzymatic degradation in the gastro intestinal tract utilizing hot-melt extrusion technology for improved absorption.

Methods: Preliminary studies were performed to select the appropriate lipids. Selected ratios of CA and lipids were extruded using a twin screw hot-melt extruder. Extrudates obtained were milled to obtain floating granules and were further evaluated for drug content, floating strength and micromeritic properties. In vitro drug release studies were performed in 900 mL of simulated gastric fluid (without enzyme) of pH …

Topical Formulation For Stimulating Sweat Secretion As An Alternative To Iontophoresis, Tasnim Fatima

Electronic Theses and Dissertations

Sweat test or pilocarpine iontophoresis test is the existing method for diagnosis of cystic fibrosis that is recommended to perform at 48 hours after birth. However, the current method is painful, with several side effects such as full thickness skin burn, skin rash, erythema etc. Therefore, the purpose of this study is to develop a pilocarpine topical formulation which can stimulate sweat secretion when applied on skin without iontophoresis. Several formulations with Transcutol®, polyethylene glycol 400 (PEG 400), Polyethylene glycol 200 (PEG 200), menthol and salicylic acid (SA) each at varying concentrations were screened as penetration enhancers. In vitro penetration …

Predictors Of Dental Opioid Analgesic Prescribing, Opioid Use And Dental Emergency Department Visits In The Mississippi Medicaid Population, Chukwuebuka Dibie

Electronic Theses and Dissertations

OBJECTIVES: The objectives of this study were: (1) to determine prevalence of opioid analgesics prescribing for non-ED dental related visits in the Mississippi Medicaid population, (2) to assess predictors of receiving opioid analgesics following non-ED dental related events among Mississippi Medicaid beneficiaries, and (3) to determine prevalence of opioid analgesic prescribing for dental related emergency departments (ED) visits in the Mississippi Medicaid population. METHODS: A retrospective, cross-sectional, observational database analysis using Mississippi Medicaid administrative claims data from January 1, 2015 to December 31, 2016. Beneficiaries with dental related visits were included in this study. Descriptive statistics were utilized to assess …

Fluorinated Organic Molecules For Medicinal Applications, Munia Sowaileh

Electronic Theses and Dissertations

The significant applications of fluorinated molecules in the pharmaceutical, agrochemical, and material sciences make them attractive synthetic targets. Difluoromethylation methods are of exceptional value and a limited number of techniques are available to perform that transformation. The primary method for introducing CF2 groups is through the use of difluoroenolates. Difluoroenolates can be generated from α-keto pentafluoro gem -diols under mild conditions. The process involves the cleavage of carbon-carbon bond and the release of trifluoroacetate. The release of trifluoroacetate is a versatile method to generate fluorinated molecules. We explored the utility of this method in generating various fluorinated moieties including α,α-difluoroketones, …

Novel Application Of Twin Screw Extruder On Production Of Diverse Formulations, Xingyou Ye

Electronic Theses and Dissertations

Twin-screw extruder has attracted considerable attention in the pharmaceutical industry as an alternative processing instrument due to its advantages compared to other conventional equipment, such as economical processing, small footprint, reduced in-process times, solvent-free and continuous processing. These superiorities have led to the application of twin-screw extruder to produce numerous dosage forms, including pellets, tablets and films. Many other formulations production can also be beneficial from the introduction of twin-screw extruder to the process. Nanocrystal formulations are promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods …

Preparation And Evaluation Of Valacyclovir Hydrochloride Ocular Inserts By Hot Melt Extrusion Technique, Gauri Shadambikar

Electronic Theses and Dissertations

The objective of the current study was to investigate the processability of Hot Melt Extrusion to formulate Ocular Inserts of Valacyclovir Hydrochloride and Evaluate its drug release in vitro and in vivo. Valacyclovir is the prodrug of Acyclovir, which is used in treatment of ocular keratitis and HSV infections. The bioavailability of the prodrug is better than the acyclovir and it is proved to permeate extensively through the corneal barrier. The polymer of choice was Klucel® Pharm MF and JF grades for the study. To optimize the formulation, different physical mixtures of the polymers and plasticizers (PEG 400 and Propylene …

Synthesis Of 2,4,6-Substituted Pyrrolo[2,3-D]Pyrimidines As Potential Anticancer Agents, Si Yang

Electronic Theses and Dissertations

This thesis mainly focuses on the introduction of the background and work have been done in the areas of antifolates development, such as folate function, its three uptake mechanisms inside human cells, antifolates’ role in chemotherapy, et. al. In addition, the Structure-Activity-Relationship design rationale for the series of antifolates will also be discussed. Nevertheless, the details of synthesizing these pyrrolo[2,3-d]pyrimidines as potential antifolates have been described, including chemistry reviews on the pyrrolo[2,3-d]pyrimidine scaffold, and the challenges encountered and the solutions how to solve or improve in order to achieve better yield.

Role Of Human Arylamine N-Acetyltransferase 1 In Tumorigenesis And Cancer Biology., Marcus William Stepp

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a well-known phase II metabolic enzyme that has been associated with carcinogenesis. Its role in the biotransformation of aromatic and heterocyclic amine carcinogens has been investigated for many years, but more recent investigations focus on a possible endogenous role of human NAT1 in cancer initiation and progression. To further explore and understand possible endogenous roles for NAT1, we conducted in vitro enzymatic reactions, in vivo studies using homozygous high (rapid) or low (slow) NAT2 activity congenic F344.WKY rats, and genetically modified human breast cancer cell lines. Human NAT1 and rodent NAT2 hydrolyzed acetyl-coenzyme …

Withaferin A Synergistically Enhances The Effects Of Paclitaxel Against Lung Cancer., Al Hassan Kyakulaga

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer-related deaths among both men and women in the U.S and worldwide. Today, paclitaxel (PAC) or taxol alongside platinum-based drugs is the most widely used agent as the first-line regimen for advanced NSCLC. However, due to toxicity, drug resistance, solubility and efficacy issues, efficacy has plateaued. In the present study, the potential of a novel plant-derived steroidal-lactone, withaferin A (WFA), for clinical use alongside PAC to improve efficacy against NSCLC was explored. The anticancer effects of PAC and WFA alone, and in combination against the in vitro cell proliferation, cell adhesion, migration and …

Synthesis And Characterization Of Ph/Temperature Dual Sensitive Multiblock Copolymer For Drug Delivery, Hyung Kyung Lee

Electronic Theses and Dissertations

The objective of this study was to develop a novel multiblock copolymer (MBCP) with temperature/pH dual-sensitivity which undergoes gelation at body temperature and degradation at acidic pH for controlled drug delivery applications. The MBCP with molecular weight of 42000 Da was synthesized by polycondensation between an acid-labile ketal linker, 2,2-bis(aminoethoxy)propane (BAP) and Pluronic® P104 using L-lysine diisocyanate ethyl ester (LDI) or 1,6-Diisocyanatohexane (HDI). The gelation temperature of 20% (w/v) MBCP was in the range of 29 to 31 ºC when tested with three different techniques: rheometer, test tube inversion method, and falling ball method. The polymer shopH-triggered degradation and drug …

Burden Of Illness And Pharmacoeconomic Evaluation Of Lumacaftor/Ivacaftor In Cystic Fibrosis, Pratyusha Vadagam

Electronic Theses and Dissertations

Objectives: (1) To estimate the burden of illness in cystic fibrosis (CF) using 2010-2014 Medical Expenditure Panel Survey (MEPS) data, and (2) to conduct a pharmacoeconomic evaluation of lumacaftor/ivacaftor in the treatment of CF.

Methods: The study was conducted in two parts. Part 1 involved a retrospective analysis using individuals in MEPS database with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code of 277.00 for a principal diagnosis of CF. Dependent variables were cumulative and out-of-pocket (OOP) expenditures and independent variables included patient demographics and clinical characteristics. Unweighted and weighted estimates of expenditure in CF group, …

Comprehensive Structural, Thermal And Toxicological Characterization Of 1-Ethyl-3-Methylimidazolium Alkylbenzenesulfonate Ionic Liquids, Hiranmayee Kandala

Electronic Theses and Dissertations

Synthesis and characterization of 1-ethyl-3- methylimidazolium alkylbenzenesulfonate ionic liquids for extraction of lignin from prairie cord grass have been studied. The ionic liquids (ILs) 1-ethyl-3- methylimidazolium benzenesulfonate (EBS), 1-ethyl-3- methylimidazolium toluenesulfonate (ETS) and 1-ethyl-3- methylimidazolium xylenesulfonate (EXS) have been synthesized in this research. An extensive structural, physical, thermal and toxicological characterization has been performed to understand the behavior of these ionic liquids. The reaction yield for the synthesis of EBS, ETS, and EXS ionic liquids was determined to be 91.2 ± 1.5 %, 96.1 ± 0.7 %, 99.0 ± 0.5 % respectively. Spectral analysis using NMR and FTIR confirms the …

Patient Friendly Formulations Utilizing Hot Melt Extrusion Technology, Manjeet Bhagwan Pimparade

Electronic Theses and Dissertations

This research work exhibited the new outlook of hot melt extrusion technology for orally disintegrating tablet, fast disintegration films and fixed dose combinations. Previous research demonstrated these applications by conventional formulation techniques which has inherent shortcoming of use of large amount of solvent and batch size manufacturing. This present work addressed some of the unique challenges which could provide patients ease of administration and reduce dosing frequencies, and moreover, mitigate the manufacturing challenges. For orally disintegrating tablet study, ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to …

Preparation And Characterization Of Acitretin-Loaded Niosomes For Psoriasis Treatment, Marey Abdulmootani Almaghrabi

Electronic Theses and Dissertations

Psoriasis is a chronic skin disease that manifests as impaired epidermal differentiation. The disease is typically treated with acitretin, an effective oral cytotoxic agent. However, due to its side effects, its use is highly limited. Topical delivery of acitretin may decrease the systemic toxicity and increase the drug’s bioavailability at the pathological site. However, this approach has some limitations. The decrease in skin integrity due to psoriasis could lead to escape of drug into the systemic circulation system and consequently compromise the topical approach. Also, the high instability of acitretin in the presence of heat could limit its topical application. …

Burden Of Depression Among Individuals With Irritable Bowel Syndrome(Ibs) In The Medicaid Population, Kaustuv Bhattacharya

Electronic Theses and Dissertations

Objective: to determine the period prevalence of IBS and comorbid depression among individuals with Irritable Bowel Syndrome (IBS) in multi-state Medicaid population, and to assess the impact of comorbid depression on healthcare utilization and costs among individuals with IBS enrolled in fee-for-service Medicaid program. Methods: a retrospective cohort study was conducted using 2006-2008 Medicaid analytic extract files for 39 states. Beneficiaries with IBS were identified based on any medical claims for the disease. Beneficiaries with one or more medical claims for depression during the study period were considered to have had comorbid depression. For each beneficiary, the first claim for …

Target Based Design And Synthesis Of Fused Pyrimidines In The Potential Treatment Of Cancer And Opportunistic Infection, Khushbu Shah

Electronic Theses and Dissertations

This dissertation describes an introduction, background and research progress in the areas of agents designed as (a) selective Pneumocystis jirovecii dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted therapy for cancer.

PCP is a host species-specific infection. Most of the drugs, synthesized and evaluated so far, have been tested against Pneumocystis carinii dihydrofolate reductase (the causative organism in rats), which would not necessarily be effective against pjDHFR (the causative organism in humans). Trimethoprim-sulfamethoxazole (TMP-SMX) combination, which has been …

Identification Of Cdks As Novel Targets Of Aspirin And Its Metabolites: A Potential Role In Cancer Prevention, Rakesh Dachineni

Electronic Theses and Dissertations

Background:
The pursuit of drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. Till date, although multiple CDK inhibitors have been identified and few are undergoing clinical trials, only two synthetic drugs have been approved by Food and Drug Administration (FDA) for use in the treatment of cancer. These two drugs are mainly used for the treatment of metastatic breast cancer in combination with other drugs; however they have toxicity associated with their use and extends patients life not more than 24 months. Therefore, there is an urgent need for …

Food Protein-Based Core-Shell Nanocarriers For Oral Drug Delivery Applications: (Influence Of Shell Composition On In Vitro And In Vivo Functional Performance Of Zein Nanocarriers, Md Saiful Islam

Electronic Theses and Dissertations

Oral delivery is the most preferred route for drug administration. Oral drug delivery is limited by poor physicochemical properties of drugs and physiological barriers in the gastrointestinal tract. To this end, there is a need for developing new carrier systems to enhance the oral bioavailability of poorly absorbed molecules. Food-grade biopolymers are attractive materials for developing drug delivery carriers’ due to their unique properties and proven safety. Six different core-shell nanocarriers were prepared using food-grade biopolymers including zein-casein (ZC) nanoparticles, zein-lactoferrin (ZLF) nanoparticles, zein-β-lactoglobulin (ZLG) nanoparticles, zein-whey protein isolate (ZWP) nanoparticles, zein-pluronic-lecithin (ZPL) nanoparticles and zein-PEG (ZPEG) micelles. The study …

Molecular Characterization Of The Opioid Receptors: Design, Development, And Preclinical Evaluation Of Salvinorin A-Based Molecular Probes., Adam Keasling

Electronic Theses and Dissertations

The field of salvinorin chemistry represents a novel and emerging field of opioid research. The novelty is derived from the lead pharmacophore: salvinorin A — a neoclerodane diterpenoid natural product isolated from Salvia divinorum. Salvinorin A represents a pharmacologically unique compound in that it is the first known non-nitrogenous KOR subtype-selective agonist, exhibits a comparatively safe physiological profile with no reports of toxicological effects in clinical trials, and, most importantly, has a steadily growing body of literature indicating potentially useful clinical applications (e.g. antinociceptive, anti-addictive, antipruritic, neuroprotective, etc.). This has encouraged the development of analogues as essential molecular probes to …

Development Of Phenotypic Drug Discovery Models For Tropical Parasitic Diseases, Surendra Kumar Jain

Electronic Theses and Dissertations

Malaria and visceral leishmaniasis are major killer parasitic diseases. These diseases though occur primarily in tropical countries; economic burden and overall health impacts of malaria and leishmaniasis are global. The emergence of drug-resistant and more-virulent strains of the pathogens has further amplified the problems. New drug discovery approaches primarily rely on in vitro and in vivo models of the disease. The pathogens causing leishmaniasis and malaria are intracellular. Leishmania parasite grows as amastigotes in macrophages cells, and malaria parasite grows within the hepatocytes or erythrocytes. The intracellular forms of the pathogens are responsible for the pathophysiology of the diseases. New …

Phytochemical Investigation Of Psychoactive Medicinal Plants For The Treatment Of Neurological Disorders, Vedanjali Gogineni

Electronic Theses and Dissertations

Neurological disorders include disorders such as migraine, tension-type headaches, Parkinson’s disease (PD), epilepsy, dementia, and Alzheimer’s disease (AD). Globally, PD is the second most comneurodegenerative disorder following AD. In developed countries, PD affects 1% of all population over 60 years of age. The prevalence of PD is increasing over the years and is expected to double by 2030. It is proposed that combination of dopaminergic drugs with monoamine oxidase B (MAO-B) inhibitors, anticholinergics, catechol-O-methyl transferase inhibitors, and other non-dopaminergic drugs can better alleviate levodopa-induced motor complications along with better control of motor symptoms. MAO-B inhibitors play a significant role in …

Synthesis, Chemistry, Biological Evaluation And Structure-Activity Relationships Of Rac- And Chiral 6-Desmethyl-5Β –Hydroxy-D-Secoartemisinin And Analogs, Mohamed Elsideiq Jihan

Electronic Theses and Dissertations

The prevention and cure of malaria is difficult as it thrives under poor socio- and pharmacoeconomic conditions in third world, tropical and subtropical regions. It is a parasitic disease spread through the bite of an infected Anopheles mosquito. In humans, malaria can be caused by several Plasmodium species that include: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi. The natural product artemisinin is a sesquiterpene lactone with an endoperoxide bridge isolated from the Chinese annual herb qinghao (Artemisia annua L or sweet wormwood). The relatively stable endoperoxide bridge is essential for their antimalarial activity. The synthesis of …