Chemical Engineering Commons^™

Qsar Modeling Of Chemical Penetration Enhancers Using Novel Replacement Algorithms, Hui Qiu

Theses

The applications of transdermal delivery are limited because of the resistance of the skin to drug diffusion. Only potent drugs, with molecular weight less than 500 Da, are suitable to cross the skin barrier. Chemical Penetration Enhancers (CPEs) are used to promote the absorption of solutes across the dermal layers. In this investigation, a Quantitative Structure-Activity Relationship (QSAR) model is applied to relate chemical penetration enhancer structures with the flux enhancement ratio through a statistical approach.

A database, consisting of 61 non-polar CPEs, is selected for the study. Each compound is represented by 777 QSAR descriptors, which encode the physical …

Power Dissipation And Mixing Time In A Partially Filled Pharmaceutical Reactor Equipped With A Retreat-Blade Impeller At Different Fill Ratios, Aniruddha Banerjee

Theses

Glass-lined, stirred reactors and tanks are of significant industrial importance, especially in the pharmaceutical and fine chemical industries. These reactors are manufactured with a “glass-lining,” i.e., a glass layer applied to the agitator, the inside of the reactor/tank and to any of the surfaces in contact with its contents in order to maximize corrosion resistance, facilitate reactor cleaning, and minimize product contamination. Because of glass-lining fabrication issues, a retreat blade impeller with a low impeller clearance off the tank bottom is commonly used in glass-lined reactors. In addition, since wall baffles cannot be easily mounted on the wall of glass-lining …

Separation Of Various Organic-Organic And Aqueous-Organic Solutions Via Pervaporation, John Tang

Dissertations

Pervaporation, an energy saving separation process, can be useful in pharmaceutical processing. However, the organic solvents involved in pharmaceutical product synthesis are chemically demanding; very few polymers are able to withstand them. An ideal membrane would be polymeric having a high thermal, chemical and mechanical stability. Such a membrane is made of a copolymer of polydimethyldioxole and tetrafluoroethylene known as PDD-TFE of the CMS-3 variety with a very high free volume. This novel membrane is used to separate a variety of organic-organic and aqueous-organic mixtures. An earlier study based on water-ethanol-isopropanol has shown evidence that the membrane selectivity may be …

Particle Engineering Via Surface Modification During Micronization For Pharmaceutical Applications, Xi Han

Dissertations

Improving the dissolution rate of Biopharmaceutics Classification System (BCS) class II drugs is an important research area. Micronization which can increase the specific surface area is a promising method to improve the dissolution rate. Micronization alone, however, can lead to downstream processing problems related to poor flow and dispersion properties. The importance of the flowability of pharmaceutical powders is well-documented in the literature. It is, therefore, important to develop a method that can simultaneously overcome these processing issues and allow for micronizing the API. In this work, dry particle coating technique is investigated in the context of micronizing API powders …

Mathematical Modeling Of Heavy Metals Diffusion And Removal From Cylindrical Cement Forms Coated With Bio-Film, Mojdeh Tabatabaie

Dissertations

A mathematical model is developed to predict bioleachi ng of heavy metals from long cylindrical shape cementitious samples. In this model, the metal concentration difference within the solid and its surface is considered as the main driving force for transport of metals to the surface of a sample at a given temperature and pressure. Fick’s first and second law are applied to explain the motion of contaminants in a long and uniform cylindrical solid. In addition, the model considers Michaelis-Menten type kinetics, a special case of the widely accepted Langmuir-Hinshelwood reaction mechanism, at the surface of the encapsulating cylinder. The …

Investigation Of The Fracture Phenomena During The Milling Process Of Inorganic Particulates And Brittle Fracture Of Polymer Composites Using Fractal Theory, Zheng Qian

Dissertations

This dissertation investigates the applicability and usefulness of applying Fractal mathematics and to the fracture of brittle particulates in Fluid Energy Mill devices, and in particular quantifying the resulting power law particle size distributions, examining the Surface Fractal Dimension of milled particulates, and relating the Izod Impact Strength values of composites of polypropylene and Calcium carbonate particulates which are large un-milled, small milled, as well as small and produced by the simultaneous milling and coating with nano-silica to the Surface Fractal Dimension of the impact fracture surfaces.

First, the dissertation examines the behavior of un-coated and micron-sized wax pre-coated particulates …

Desalination Of Brine And Produced Water By Membrane Distillation At Lower As Well As Higher Temperatures And Pressures, Dhananjay Singh

Dissertations

Direct contact membrane distillation (DCMD)-based desalination process is a thermally- driven separation process where a hydrophobic microporous membrane separates a hot brine feed and a cold distillate which condenses the water vapor from the hot brine passing through the membrane pores. So far, DCMD has been explored for hot brines and other aqueous solutions below 100oC. For feed solutions above 100oC, DCMD has an extra advantage over other conventional separation processes like reverse osmosis (RO) which requires cooling of the feed solution costing additional energy; further, RO can not utilize the heat available in the feed solution. Produced water obtained …

Hydrodynamic Effects Of An Arch-Shaped Fiber Optic Probe In A Dissolution Testing Apparatus 2, Yiran Zhang

Theses

Dissolution testing is widely used in the pharmaceutical industry to evaluate newly developed drug formulations and as a quality control method to insure that solid dosage forms have consistent dissolution property. Typically, samples are manually drawn from the dissolution vessel prior to analysis. An approach to overcome the limitations of manual sampling consists in the use of sampling probes, such as fiber optic probes, permanently inserted in the dissolution medium and continually sampling the drug concentration in it as the solid dosage form dissolves. Despite their advantages, permanently inserted fiber optic probes can alter the normal fluid flow within the …

Single And Multiphase Mixing In Partially Filled Stirred Vessels, Shilan Motamedvaziri

Dissertations

In many industrial applications, mixing vessels have a liquid height-to-tank diameter ratio, H/T, equal to, or larger than 1. However, there are many instances where this ratio is lower than 1, as in all those cases in which the vessel is either emptied or filled. Even when H/T<1, sufficient agitation must still be provided in order to attain the desired process objectives. When the impeller submergence is reduced as a result of lowering the liquid level, the fluid dynamics of even a single-phase stirred liquid can become quite complex, with different regimes possibly existing depending on the geometric characteristics of the system (such as impeller clearance, liquid height, or liquid submergence above the impeller). The objectives of this work were to study in detail the hydrodynamic changes that occur when H/T is decreased, and to determine the minimum liquid levels and the critical impeller submergence for different impeller off-bottom distances, impeller diameters and agitation speeds where adequate mixing process can still be achieved, both in a single liquid phase and in solid-liquid suspensions.

Flat-bottomed, baffled vessels (5L, 12L, 20L and 170L) equipped with a single disk turbine (DT) of four different sizes placed at five different impeller off-bottom clearances were used here to study the system's hydrodynamics and related mixing phenomena. A number of experimental tools were used to analyze the systems under investigation, including: …

Hot-Melt Mixing Of Partially Miscible Active Pharmaceutical Ingredient-Polymer Mixtures, Min Yang

Dissertations

Solid dispersion/solution processes for producing pharmaceutical oral dosages such as hot-met extrusion (HME) have received increasing attention by industry and academe because they can enhance drugs’ solubility and even bioavailability to a great extent by converting drugs from crystalline to amorphous form. HME can be carried out at two process temperature regimes: one where T_process > T_m of the drug and the T_g of the polymer (or the T_m for the case of semi-crystalline polymers); the other at T_m > T_process > T_g (T_m for the case of semi-crystalline polymer). Processing below the drug’s …

Preparation Of Different Polyamide Nanofiltration Membranes By Interfacial Polymerization And The Effect Of Post-Polymerization Treatment On Separation Performance, Yu Qin

Theses

Interfacial polymerization (IP) is a powerful technique for fabrication of thin film composite (TFC) membranes. In this study, polyamide nanofiltration (NF) composite membranes ware prepared by interfacial polymerization of polyethylenimine (PEI) or m-phenylene diamine (MPD) with isophthaloyl dichloride (IPD) on the surface of a porous polyethersulfone (PES) support. Concentrations of monomer reactants for this reaction were decided by equivalent weight ratio. A standard IP procedure was applied to successfully coat PES flat films. After preparation, three different post-polymerization treatments were employed and one optimal treatment was proven after membrane testing.

The TFC flat film membranes were characterized by nanofiltration of …

Combustion Dynamics Of Individual Reactive Material Particles, Carlo Francisco Badiola

Theses

Metallic reactive powders are widely used as solid fuels, pyrotechnic materials, and components of enhanced blast explosives. Metals are attractive because of their high combustion enthalpies and temperatures. Quantitative descriptions of the combustion processes and mechanisms for both pure metal and composite particles are also desired for their proper implementation in specific applications. Among reactive metals, Al is used most widely and its combustion has been studied extensively. A recently developed experimental setup using laser-ignited metal powders enabled one to record optical signatures for time-resolved combustion instances for 2-25 µm diameter aluminum particles burning in different atmospheres. Individual particle diameters …

Theoretical Prediction Of Drug Release In Gi Tract From Spherical Matrix Systems, Naga Lakshmi Ramana Susarla

Dissertations

The significance of controlled release drug delivery systems (CRDDS) lies in their ability to deliver the drug at a steady rate thus reducing the dosage interval and providing a prolonged pharmacodynamic effect. But despite the steadily increasing practical importance of these devices, little is known regarding their underlying drug release mechanisms. Mathematical modeling of these drug delivery systems could help us understand the underlying mass transport mechanisms involved in the control of drug release. Mathematical modeling also plays an important role in providing us with valuable information such as the amount of drug released during a certain period of time …

Effects Of Operating And Geometric Variables On Hydrodynamics And Tablet Dissolution In Standard And Modified Dissolution Testing Apparatuses 2, Yimin Wang

Dissertations

Dissolution testing is routinely conducted in the pharmaceutical industry to provide critical in vitro drug release information for quality control purposes, and especially to assess batch-to-batch consistency of solid oral dosage forms such as tablets. Among the different types of apparatuses listed in the United States Pharmacopoeia (USP), the most commonly used dissolution system for solid dosage forms is the USP Dissolution Testing Apparatus 2, consisting of an unbaffled, hemispherical-bottomed vessel equipped with a 2-blade radial impeller.

Despite its extensive use in industry and a large body of work, some key aspects of the hydrodynamics of Apparatus 2 have received …

Multifunctional Reactive Nanocomposite Materials, Demitrios Stamatis

Dissertations

Many multifunctional nanocomposite materials have been developed for use in propellants, explosives, pyrotechnics, and reactive structures. These materials exhibit high reaction rates due to their developed reaction interfacial area. Two applications addressed in this work include nanocomposite powders prepared by arrested reactive milling (ARM) for burn rate modifiers and reactive structures. In burn rate modifiers, addition of reactive nanocomposite powders to aluminized propellants increases the burn rate of aluminum and thus the overall reaction rate of an energetic formulation. Replacing only a small fraction of aluminum by 8Al•MoO₃ and 2B•Ti nanocomposite powders enhances the reaction rate with little change …

Effect Of Dry Particle Coating On The Properties Of Cohesive Pharmaceutical Powders, Lauren Elizabeth Beach

Dissertations

Engineered particles, which have undergone surface modification via dry coating, have been previously shown to have improved flow and handling properties. The improvements in these properties can be applied and are very useful for a number of industrial applications, in this case the pharmaceutical industry. This work investigates the effect of dry particle coating to improve the flowability of cohesive active pharmaceutical ingredient (API) powders and their blends. Improving the flow properties of cohesive API powders can significantly improve their handling and subsequent use for pharmaceutical processes such as formulation and manufacturing processing operations. Although it has been shown that …

Electrodeless Electro Hydrodynamic Printing Of Personalized Drug Dosages, Ezinwa Okeoma Elele

Dissertations

There is compelling evidence that variability in drug efficacy in individuals depends on their genetic fingerprints. These observations have given rise to the concept of personalized therapy whose ultimate goal is to develop medicinal agents designed for each niche of the population and individual patients according to their genetic background. The drawback in current pharmaceutical technologies is that most processes are designed to target large population and are unable to meet the demand of small-scale manufacturing of tailored therapeutics with diverse range of physical properties. One of the major challenges lie in developing efficient and cost effective methods of manufacturing …

Deagglomeration And Mixing Via The Rapid Expansion Of High Pressure And Supercritical Suspensions, Daniel To

Dissertations

Nano-materials are the focus of many research activities due to the desirable properties imparted from their small grain size and high interfacial surface area. However, these materials are highly cohesive powders in the dry state and typically form large agglomerates, leading to a diminished surface area or even grain growth, which minimizes the effectiveness of these nanomaterials. This dissertation addresses the issue of mixing nanopowders constituents by deagglomerating them and achieving simultaneous mixing so that even after inevitable reagglomeration, the effectiveness of large interfacial surface area may be preserved.

Nano-particle mixtures were prepared using the environmentally benign dry mixing methods …

Dissolution Testing Of Prednisone And Salicylic Acid Calibrator Tablets At Different Tablet Locations, Anandhavalavan Arulmozhi

Theses

Dissolution testing is routinely carried out in the pharmaceutical industry to determine the rate of dissolution of solid dosage forms. This test is one of the several tests that pharmaceutical companies typically conduct on oral dosage formulations (e.g., tablets) to determine compliance. The USP Dissolution Testing Apparatus 2 is the most common of the apparatuses listed in the USP. However, it has been shown previously that the dissolution profile of a tablet undergoing dissolution in the USP Dissolution Apparatus 2 can be affected by the tablet location in the apparatus.

In this work, the dissolution rates of both non-disintegrating tablets …

Dissolution Of Disintegrating Solid Dosage Forms In A Modified Dissolution Testing Apparatus 2, Shrutiben Rameshbhai Parekh

Theses

Dissolution tests are routinely carried out in the pharmaceutical industry to determine the dissolution rate of solid dosage forms. Dissolution testing serves as a surrogate for drug bioavailability through in vitro–in vivo correlation (IVIVR), and it additionally helps in guiding the development of new formulations and in assessing lot-to-lot consistency, thus ensuring product quality. The United States Pharmacopoeia (USP) Dissolution Testing Apparatus 2 is the device most commonly used for this purpose. Despite its widespread use, dissolution testing using this apparatus remains susceptible to significant error and test failures. There is documented evidence that this apparatus is sensitive to several …

Transdermal And Transbuccal Delivery Of Lidocaine And Nicotine : Combined Effects Of Iontophoresis And Chemical Enhancers, Ran Wei

Theses

This study focused on the effects of iontophoresis and chemical enhancers on drug release. The transport of Lidocaine HCl (LHCl) and Nicotine Hydrogen Tartrate (NHT) through the skin and mucosa was evaluated for potential clinical applications. These two potential delivery routes have the advantage of avoiding first-pass effect. Samples were pretreated with enhancer solutions for one hour before the experiments. Passive or 0.3 mA iontophoresis-assisted drug diffusion was conducted for 8 hours to monitor the cumulative amount of drug released. Graphical methods and mathematical optimization techniques were implemented to analyze the data. The effects of chemical enhancers on the delivery …

Investigation Of The Potential Catalytic Activities Of Several Metal Organic Framework (Mof) Materials, Guangyu Zhang

Theses

Metal-organic frameworks (MOFs) are promising porous materials due to their high porosities, large apparent surface areas, tunable pore properties and selective uptake of small molecules. Many researches have been focused on developing new MOF structures and exploring their use in gas storage and separation. Only few studies investigated the catalytic properties of MOFs. In this study, catalytic properties are explored over several MOFs including zeolitic imidazolate framework-8 (ZIF-8), Ni(FA) and Zn(FA). These MOFs are used as catalyst supports for iron or platinum nanoparticles. The catalysts are prepared using incipient wetness impregnation method and characterized with Brunauer-Emmett-Teller (BET), pulse chemisorption, X-ray …

Thermochemical Properties, Bond Energies And Internal Rotor Potentials In Methyl Ethyl Sulfide And Oxygenated Sulfur Hydrocarbons Intermediates For Modeling Its Combustion And Atmospheric Chemistry, Guanghui Song

Theses

Small (1 to 4 carbon) hydrocarbon sulfides and thiols are formed in the biosphere by microorganisms and subsequently emitted into the lithosphere, hydrosphere and atmosphere. In the atmosphere they are oxidized by photochemical and radical reactions to intermediate hydrocarbon and to sulfur oxides. The oxides of these sulfur compounds and the intermediates from the oxidation process are known to form aerosols that can counteract the global warming green house effect. Recent studies also suggest that some aerosols can also contribute to global warming. Sulfur oxides are also major contributors to acid rain as the results of the atmospheric chemistry oxidation …

Study Of The Heating And Ignition Of Metal Powder By Electrostatic Discharge, Ervin Beloni

Dissertations

The objective of this work was to understand the processes that lead to ESD stimulated ignition events in metal powders. Several metals were studied: Mg, Al, and Ti. A commercially available ESD test device was adapted for the present experiments. The ESD current and voltage were measured using inductance coils; the data were used to determine the electric circuit impedance, and energy transferred to the powder. A mode of the powder ignition (individual particles vs. dust cloud), ignition delays, burn times, and velocities of ignited and ejected particles were determined from optical measurements.

It was determined that the ESD energy …

Study Of Controlled Release Of Active Pharmaceutical Ingredients From Functionalized Nanoclays And Polymer Matrices, Jin Uk Ha

Dissertations

This dissertation contains the results of three related novel investigations in the field of structure-property-processing relationships of pharmaceutical polymer-based products. They are: a) modification of a pharmaceutical anionic nanoclay with two different Active Pharmaceutical Ingredients (APIs) to produce nanohybrid API carriers intended to be used alone or in acrylic polymer matrices, b) comparison of binary systems containing the above APIs in the selected acrylic polymers in terms of their miscibilities with the polymer, but in the absence of nanoclay, and c) comparison of the polymer/API binary systems with ternary polymer/API/Clay systems.

For the first study, the calcination method which can …

Study Of Controlled Release Of Dapsone From Modified Montmorillonite And Polymer Matrices, Jia Fan

Theses

This thesis focuses on the controlled release system of Dapsone (DAP) as the Active Pharmaceutical Ingredient (API) intercalated into sodium montmorillonite (MMT-Na+) and their combination with an anionic copolymer (Eudragit® S100). The effects of the excipients on the API dissolution rate were studied from their release profile in simulated intestinal fluid (pH=7.4) at 37±0.5°C. In the first part of the research, ionizable Dapsone was intercalated in the interlayers of MMT-Na+ to produce a nanohybrid. In the second part of the research, the nanohybrid was melt dispersed in the polymer to produce ternary (API/ Clay/ Polymer) composites. For comparison, API-polymer solid …

Design Of Novel Drug Delivery System And Optimal Dosage Regimens, Kwang Seok Kim

Dissertations

Three representative drug delivery systems were analyzed to emphasize the roles of mathematical models and computer-aided simulations in pharmaceutical research. In the first project, a protocol was developed so that the optimal regimen, consisting of the intravenous boluses and subsequent infusion of theophylline, could be obtained once information on the pharmacokinetics became available. The method was based on a two-compartment model of the human body. A module was created and posted on a website for free access. The second project dealt with the transdermal heat-assisted delivery of corticosterone. Heat conduction and drug diffusion through the patch and the skin were …

Design Of Drug Delivery Strategies Based On Well-Stirred Experiments, Kumud Kanneganti

Theses

Drugs are generally administered to the human body via injections (IV) or through other paths such as the buccal, nasal routes. The main consideration when designing a medication schedule is to maintain a therapeutic level of the drug in the body during the course of treatment. To achieve this goal, when IV drug therapy is selected, particular importance has to given to the dose to be injected and how to maintain the concentration of the pharmaceutical active ingredient (API) in the body between a Minimum Toxic Concentration (MTC) and a Minimum Effective Concentration (MEC). This therapeutic range varies with the …

Minimum Agitation Speed For Solid Suspension And Mixing Time In A Torispherical -Bottomed Pharmaceutical Stirred Tank Under Different Baffling Conditions, Dilanji Bhagya Wijayasekara

Theses

The minimum agitation speed, NS, required to just suspend solid particles dispersed in water was experimentally determined in this work for a glass-lined type of mixing tank provided with a torispherical bottom and agitated with a retreat-blade impeller under different baffling configurations. Ns for the same tank but equipped with a different agitation system, namely an axial impeller, was also experimentally determined for the purpose of comparing of performances of the two systems. The effect of impeller off- bottom clearance and the vessel's liquid level on the minimum agitation speed were also experimentally studied. Njs, was experimentally determined …

Experimental Investigation Of Mixing Time In A Stirred, Torispherical-Bottomed Tank Equipped With A Retreat-Blade Impeller, Nonjaros Chomcharn

Theses

Glass-lined reactors are typically used in the pharmaceutical and specialty chemicals industries because of their material compatibility with most reactants and their cleanability. These reactors are typically equipped with a retreat-blade impeller placed close to the bottom of the tank a single baffle mounted from the top. The mixing performance of such reactors has not received significant attention in the literature, despite their ubiquitous presence in the pharmaceutical industry. In particular, mixing time, i.e., the time required by the system to achieve a predefined level of homogeneity, has not been studied to any significant degree.

In this work, the mixing …