Pharmacy and Pharmaceutical Sciences Commons^™

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

A Detailed Parameter Study Into The Dermal Absorption Of Chemical Warfare Agents And The Effects Of Pharmacokinetics, Koko Lear

Theses

Chemical warfare agents (CWAs) are substances of varying toxicity profiles. These chemicals exhibit complex dynamics and pose a serious health risk when released into the environment. A mathematical model based on Fick’s second law of diffusion was developed to comprehend how these compounds were absorbed into the skin. The analysis applied to both small and large doses and, successfully, predicted experimental results. This work also includes the effects of CWA physicochemical properties on evaporation and dermal absorption through the stratum corneum. A sensitivity analysis was conducted to assess the impacts of small variations in the initial dose, environmental conditions, and …

Towards Quality By Design (Qbd) Of Pharmaceutical Oral Films Loaded With Poorly Watersoluble Drugs, Eylul Cetindag

Dissertations

Oral films are an emerging drug delivery dosage form with numerous advantages such as ease of handling, the possibility to circumvent the first-pass metabolism, better patient compliance, capability for continuous manufacturing, and as a platform for personalized medicine. As films are different from other final dosages by their dimensions and their matrix form, further research is required to better understand the impact of excipient and drug on product performance to assure a consistent and good quality product. Therefore, this dissertation aims to contribute towards the processability and manufacturability of films by examining the impact of the materials and processes. First, …

Exploring Fused Deposition Modeling (Fdm) Three-Dimensional Printing Tablet Design Options For Pharmaceutical Dosage Forms, Guluzar Gorkem Buyukgoz

Dissertations

This dissertation examines the use of Fused Deposition Modeling (FDM) based three-dimensional (3D) printing approach for developing patient-specific dosage forms and addressing related technical challenges in such drug delivery systems. The first main objective is to explore pharmaceutical tablet design options using novel FDM 3D printing technology as the drug delivery platform such that drug form and tablet properties are tailored by considering patient age-specific formulations and dissolution control. Of the five different design options, two proposed options meet the main objective of providing similar drug release, whereas the popular option of fixed drug concentration but differing tablet size could …

Formulation Strategies To Enhance Solubility And Permeability Of Small Molecules For Drug Delivery Applications, Pradeep Kumar Bolla

Open Access Theses & Dissertations

All the new chemical entities/drug molecules intended for therapeutic use must be administered using an appropriate delivery system/dosage form to achieve maximum bioavailability. However, designing a drug delivery system is complex as several factors such as lipophilicity, molecular mass, crystallinity, ionic charge, polymorphic forms and hydrogen bonding) affect the solubility and permeability of these molecules. Biopharmaceutics drug classification system (BCS) categorizes the existing drugs into four classes based on the aqueous solubility and membrane permeability and it is reported that >70% of the drugs are poorly soluble and belong to BCS class II and BCS class IV. Several physical, chemical …

Effect Of 3d Printed Tablet Shape On Drug Release Profile, Christina Gedeon

Theses

There is a growing interest in utilizing additive manufacturing (AM) as a manufacturing tool to develop oral tablets for personalized medicine. This ultimate goal in mind, this study explores the feasibility of extrusion-based fused deposition modeling (FDM) to 3D print oral tablets with tunable design to control drug release profile. Tablets are printed using poly(vinyl alcohol) (PVA) loaded with model drugs: acetaminophen and caffeine. Hot melt extrusion (HME) is used to fabricate PVA filaments loaded with acetaminophen and caffeine. These filaments are used to fabricate a range of tablets with varying designs to prepare immediate and delayed release tablets. Thermal …

Modelling In Vitro Dissolution And Release Of Sumatriptan Succinate From Polyvinylpyrrolidone-Based Microneedles Aided By Iontophoresis, James Paul Ronnander

Dissertations

A novel dissolving microneedle array system is developed to investigate permeation of a sumatriptan succinate formulations through the skin aided by iontophoresis. Three formulations consisting of hydrophilic, positively charged drug molecules encapsulated in a water-soluble biologically suitable polymer, polyvinylpyrrolidone (PVP), have been accepted by the U.S. Food and Drug Administration (FDA). The microneedle systems are fabricated with 600 pyramid-shaped needles, each 500 µm tall, on a 0.785-cm² circular array. In vitro transdermal studies with minipig skin and vertical Franz diffusion cells show > 68% permeation of sumatriptan over a 24-hour period. A combination of microneedle and electrical current density ranging …

Roles Of Surfactant And Binary Polymers On Dissolution Enhancement Of Bcs Ii Drugs From Nanocomposites And Amorphous Solid Dispersions, Md Mahbubur Rahman

Dissertations

Drug nanocomposites and amorphous solid dispersions (ASDs) are two major formulation platforms used for the bioavailability enhancement of BCS Class II drugs. The major drawback of nanocomposites is their inability to attain high drug supersaturation during in vitro (<50% relative supersaturation) and in vivo dissolution. On the other hand, formulating an amorphous solid dispersion (ASD) with high drug loading (>20%) that releases drug rapidly, while generating and maintaining high supersaturation over at least three hours is challenging. The goal of this thesis is to develop a fundamental understanding of the impact of anionic surfactants–polymers on in vitro drug release from nanocomposites and ASDs, while addressing the above challenges. To achieve this goal, the following objectives are set: (1) compare griseofulvin …

Application Of Electrostatic Dry Powder Coating Technology On Hard Capsules, Zhehao Jing

Electronic Thesis and Dissertation Repository

This project applied electrostatic dry powder coating technology on hard gelatin and HPMC capsules using Eudragit^® RS/RL and Eudragit^® L 100-55 to achieve sustained release and enteric release respectively. Dry powder coating eliminated the difficulties associated with conventional liquid coating processes such as poor adhesion and stickiness for capsules. Additionally, through optimizing sprayed plasticizer volume, the coating powders deposited on the capsules could be efficiently maximized. The weight gain of coating and the formulation of coating materials were important parameters which controlled the release profiles of coated capsules. The release mechanism of coated capsules was quite different from …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Process Analytics From Passive Acoustic Emissions Monitoring During Fluidized Bed Pellet Coating In Pharmaceutical Manufacturing, Allan Carter

Electronic Thesis and Dissertation Repository

Piezoelectric microphones were attached to a top spray fluidized bed to provide valuable process signatures. Relationships were developed between sound waves and conditions within the fluidized bed to relay critical quality and performance information. Deep learning analytics were used to extract valuable information from experimental data. Advancements in passive acoustic emissions monitoring will play a key role in optimizing pharmaceutical manufacturing pathways to ensure drug quality and performance.

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

Understanding The Thermodynamics And Oral Absorption Potential Of Pharmaceutical Amorphous Solid Dispersions, Nico Setiawan

Theses and Dissertations--Pharmacy

Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such …

Design And Analysis Of Curcumin Conjugated Poly(Beta-Amino Ester) Networks For Controlled Release In Oxidative Stress Environments, Carolyn T. Jordan

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress, the imbalance of free radical generation with antioxidant defenses, leads to cellular inflammation, apoptosis and cell death. This compromised environment results in debilitating diseases, such as oral mucositis (OM), atherosclerosis, and ischemia/reperfusion injury. Antioxidant therapeutics has been a proposed strategy to ameliorate these imbalances and maintain homeostatic environments. However, the success of these approaches, specifically curcumin, has been limited due to characteristics such as hydrophobicity and high reactivity when released as bolus doses to contest to oxidative stress induced diseases. The development of a controlled release system to aid in protection of the antioxidant capacity of curcumin, as …

Comparative Analysis Of The Dissolution Performance Of Aspirin Tablets In The Usp Apparatus 2 And In A Minivessel Dissolution System, Annmarie C. Walker

Theses

Dissolution testing is a critical component of quality control procedures in the pharmaceutical industry in order to ensure that the final solid dosage forms have consistent dissolution properties. Dissolution tests are also routinely conducted to evaluate the in-vitro performance of solid dosage forms during pharmaceutical development, to aid in the behavior of formulations, and to optimize drug release from dosage forms.

The use of compendial dissolution test apparatus and techniques, such as the USP 2 (Paddle), to characterize the dissolution performance of oral drug delivery system is an established area of pharmaceutical science. However, this method is not always appropriate, …

Computational And Experimental Determination Of The Mixing Efficiency Of A Microfluidic Serpentine Micromixer, Siril Arockiam

Theses

In microfluidics, efficiency and mixing time are the greatest disadvantages. These parameters hinder the application of microfluidic devices for biochemical and immunological assays. However, once these disadvantages have been overcome by optimizing the parameters of the microfluidic device, it becomes the important analytical tool. In this experiment, various designs of microfluidic devices have been both simulated using COMSOL software, and experimentally verified to obtain the optimized parameter such as depth and velocity for better mixing efficiency. The COMSOL model has been validated by comparing the results with fluorescent images data of the experiment. The microfluidic device is built with Adhesive …

Green Chemistry Oxidative Modification Of Peptoids Utilizing Bleach And Tempo, Jesse Leland Roberts

Graduate Theses and Dissertations

Biotherapeutic drugs, derived from biological molecules such as proteins and DNA, are becoming an integral and exceptionally critical aspect of modern medicine. Compared to common pharmaceutical drugs, biotherapeutics are much larger in size and have greater target specificity, allowing them to treat many chronic diseases ranging from cancer to rheumatoid arthritis. The major issue with protein based therapeutics is that they readily undergo proteolysis, or enzymatic degradation, when administered through subcutaneous injections. Traditionally, biotherapeutic modification procedures have centered on the use of PEG derivatives. This process, called PEGylation, is unfavorable due to the increases in molecular weights of the proteins …

Power Dissipation And Power Correlations For A Retreatblade Impeller Under Different Baffling Conditions, Chadakarn Sirasitthichoke

Theses

Glass-lined stirred reactors and tanks are commonly used in the pharmaceutical industry because of their corrosion resistance, ease of cleanliness and minimization of product contamination. Most industrial glass-lined tank reactors are provided with a torispherical tank bottom and a retreat curve impeller with low impeller clearance from the vessel bottom. The power, P, dissipated by the impeller is a critical process parameter to mixing processes to achieve the desired mixing effect, especially since the power per unit volume, P/V, directly controls mass transfer processes and other mixing phenomena. However, little information has been published about the power dissipation and the …

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 …

Computational And Experimental Determination Of The Hydrodynamics In A Stirred Unbaffled Vessel Provided With Angle-Mounted Axial Impellers, Ji Ma

Theses

In most industrial applications, stirred tanks and reactors are typically provided with baffles to improve their mixing characteristics. However, in a number of pharmaceutical production facilities unbaffled vessels are commonly used. The absence of baffles is preferred in such cases because it reduces the potential for contamination and makes cleaning the vessel between batches easier. However, the lack of baffles also has a negative impact on the system’s hydrodynamics since it often results in poor mixing of the batch, especially if the impeller is centrally placed, since the liquid in such a system is subject to a strong tangential flow, …

Biodegradable Nano-Hybrid Polymer Composite Networks For Regulating Cellular Behavior, Charles Henley Sprague

Masters Theses

Photo-crosslinkable polymeric biomaterials have emerged in the field of biomedical research to promote tissue regeneration. For example, scaffolds that can be crosslinked and hardened in situ have been known to make suitable implant alternatives. Since injectable and photo-crosslinkable biomaterials offer the advantage of being minimally invasive, they have emerged to compete with autografts, a current highly invasive method to repair diseased tissue. A series of novel photo-crosslinkable, injectable, and biodegradable nano-hybrid polymers consisting of poly(ε-caprolactone fumarate) (PCLF) and polyhedral oligomeric silsesquioxane (POSS) has been synthesized in our laboratory via polycondensation. To engineer the material properties of the nano-hybrid networks, varied …

Experimental Determination Of Solids Suspension With Angled Impeller In A Pharmaceutical Mixing Vessel, Yingxi Tang

Theses

Angled-mounted impellers are commonly used in a number of pharmaceutical industry applications, from laboratory reactors to full-scale tanks. In these systems, the impeller is not centrally and vertically mounted, as in most stirred vessels, but it enters the vessel, and is therefore immersed in the fluid, at an angle from the vertical. This arrangement provides some baffling effects that would not otherwise exist if the impeller was centrally mounted.

One common requirement for such systems is that they are capable of suspending small solids dispersed in the liquid. Therefore, it is critical to know the value of the minimum agitation …

Experimental Determination Of The Agitation Requirements For Solids Suspension In Dissolution Systems Using A Mini Paddle Apparatus, Yang Song

Theses

Dissolution testing is a critical step in quality control of manufactured final products in the pharmaceutical industry. The United State Pharmacopeia (USP) Dissolution Testing Apparatus 2 (paddle) is the most widely used dissolution test devices in the pharmaceutical industry to formulate solid drug dosage forms and to develop quality control specifications for its manufacturing process.

Mini vessels and mini paddle dissolution testing systems are smaller versions of the USP 2 Apparatus. The concept of the mini paddle apparatus is similar to that of the USP 2 setup but it is scaled down about to 1/5 of the volume and 40% …

Effect Of Impeller Submergence On Power Dissipation And Solids Suspension In Mixing Systems Equipped With Pitch-Blade Turbines, Yufeng Song

Theses

Mixing and dispersion of solids in a liquid is a process frequently encountered in the pharmaceutical industry and often conducted in cylindrical baffled tanks stirred by mechanical impellers. In operations where the liquid level is decreased (as often which emptying the tank) the process must be stopped when the solids are no longer suspended. In this work, the minimum agitation to suspend solids (Njs) when the liquid level was lowered, and the impeller submergence S_b changed as a result were determined for the case of a six-blade, pitch-blade turbine (6-PBT) impeller. The power consumed by the impeller …

Modeling, Optimization, And Sensitivity Analysis Of A Continuous Multi-Segment Crystallizer For Production Of Active Pharmaceutical Ingredients, Bradley James Ridder

Open Access Dissertations

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the …

Hydrodynamic Cfd Modeling Of A Pharmaceutical Reactor Vessel Provided With A Retreat-Blade Impeller Under Different Baffling Conditions, Christopher G. Foehner

Theses

In the pharmaceutical industry, glass-lined reactors and vessels are often utilized to carry out a variety of different unit operations. Within these systems, both the vessel and impellers are typically glass-lined in order to provide superior corrosion resistance, prevent product contamination, and enhance cleanability. This approach, in turn, often requires the use of different, and sometimes sub-optimal, baffling conditions, which affect the hydrodynamics of the vessels and the reactor performance.

Computational Fluid Dynamics (CFD) is a computational tool that employs numerical methods and algorithms to discretize and numerically solve partial differential equations (PDEs) representing mass, energy, and momentum conservation equations …

Assessment Of A Marine Polysaccharide For Use As Excipient In Pharmaceutical Hot-Melt Extrusion, Qing Ye

Theses

Pharmaceutical Hot Melt Extrusion (HME) is currently investigated by both industry and academia as a method for manufacturing solid oral dosages with improved bioavailability of poorly-water soluble active pharmaceutical ingredients (APIs) and control drug release of water-soluble APIs. Although HME is traditionally utilizing synthetic polymers to produce such dosages, biopolymers constantly gain ground by virtue of renewability, biocompatibility and in some cases biodegradability. In this work, the possibility of using Keltone, a marine polysaccharide derived from brown seaweed, as a polymeric excipient for pharmaceutical HME is explored. Keltone is insoluble in acidic pH and soluble in basic pH, therefore making …

Experimental Determination Of The Mixing Requirements For Solid Suspension In Pharmaceutical Stirred Tank Reactors, Anqi Zhou

Theses

Glass and glass-lined, stirred-tank reactors are of significant importance in the pharmaceutical and related industries. Because of fabrication issues, a retreat blade impeller (RBI) with a low impeller clearance off the tank bottom is commonly used in glass-lined reactors, typically combined with a single baffle (providing only partial baffling conditions) mounted from the top of the reactor. In addition, these reactors are often provided with a torispherical bottom. Other configurations are also used, including full baffling or no baffles at all, hemispherical bottoms, and different impeller types. Despite their common use, some of the most important mixing characteristics of this …