Engineering Commons^™

Batch And Continuous Production Of Stable Dense Suspensions Of Drug Nanoparticles In A Wet Stirred Media Mill, Afolawemi Afolabi

Dissertations

One way to improve the bioavailability of poorly water-soluble drugs is to reduce particle size of drug crystals down to nanoscale via wet stirred media milling. An increase in total surface area per mass loading of the drug and specific surface area as well as reduced external mass transfer resistance allow a faster dissolution of the poorly-water soluble drug from nanocrystals. To prevent aggregation of nanoparticles, polymers and surfactants are dissolved in water acting as stabilizers via adsorption onto the drug crystals.

In the last two decades, ample experimental data were generated in the area of wet stirred media milling …

Pressure Swing Membrane Absorption Process For Separation Of Low Temperature Post-Shift Reactor Syngas, John Chau

Dissertations

This thesis is concerned with a cyclic pressure swing membrane absorption process (PSMAB) for separation of the feed gas mixture containing —40% CO₂-He balance using pure ionic liquid, 1-butyl-3-methylimidazolium dicyanamide ([bmim][DCA]), and its solution containing poly(amidoamine) (PAMAM) dendrimer Gen 0 primarily with a dry feed gas. An advanced pressure swing membrane absorption process is developed to produce purified He as a surrogate for H₂ at a high pressure from simulated low- temperature shifted syngas for different membrane modules. The PSMAB process also simultaneously produces a highly purified CO₂ stream containing bulk of the CO₂ in …

The Effect Of Nanoclays On The Properties Of Aspirin Modified Enteric Polymer Prepared By Hot-Melt Mixing, Nonjaros Chomcharn

Dissertations

Melt mixing in batch equipment or continuous extruders is a technique that recently gained the attention of the pharmaceutical industry. This dissertation investigates two controlled-release drug delivery systems. The first system, namely the enteric matrix, contains an active pharmaceutical ingredient (API) and plasticizer in an enteric polymer while in the second system a nanoclay is added to the enteric matrix, to produce a polymer nanocomposite. The first system employs hot-melt mixing to prepare a modified enteric matrix, as a delayed-release dosage form. Different concentrations of aspirin (ASP) ranging from 10 – 30% w/w are melt-mixed with a plasticized Eudragit® …

Reaction Mechanisms Of Hydrocarbon And Mercury Systems In The Atmosphere And In Combustion: A Theoretical Study Of Thermochemical And Kinetic Properties, Itsaso Auzmendi Murua

Dissertations

The continuing increase in the world population and the rapidly changing lifestyle and education of this population projects significant increases in energy requirements. Global warming is a worldwide major concern with a very serious potential stress on our climate threatening major changes to the environment. It is, without question, of major importance to improve the efficiency and optimize the current available combustion processes and fuel sources, to develop alternative fuels and to reduce the emissions of toxic pollutants.

The objective of this dissertation is to present thermochemical, kinetic and modeling results on two reference fuels (the land vehicle fuel isooctane …

Metal Based Reactive Nanocomposites Prepared By Cryomilling, Shasha Zhang

Dissertations

Aluminum is one of the most commonly used metal fuel additives for propellants, explosives, and pyrotechnics. Recent interest has been focused on replacements for aluminum as fuel additives to achieve higher combustion temperatures and stronger pressure pulses for applications in advanced munitions systems. Two applications are addressed in this work. In the applications for explosives designed to defeat stockpiles of chemical and biological weapons, it is of interest to develop multifunctional materials combining the high energy density of metal fuels with the biocidal activity of halogens. A challenge of this effort is to design and prepare powder-like Al-I2 materials which …

Engineering Spores To Display G Protein-Coupled Receptors For Directed Evolution, Alyssa Misoo Kim

Theses

All human cells are surrounded by a plasma membrane made from a phospholipid bilayer, which is responsible for maintaining a biologically active species, while stopping entry of deleterious substances from the outside. G protein-coupled receptors (GPCRs) are the membrane proteins, which transmit signals across the cell membrane. GPCRs are involved in almost every physiological process, and irregular control leads to pathological conditions. Therefore, they are major drug targets. Crystal structure determination is required to understand the molecular details of activation/deactivation. However, GPCRs are difficult to crystallize because of stability issues. An efficient protein engineering system needs to be developed. The …

Batch Foaming Of Hot Melt Extruded Excipient/Disintegrant/Api Pharmaceutical Formulations And The Study Of The Effects Of The Resulting Cellular Structures On Api Dissolution, Na Yao

Theses

This thesis focuses on the impact of a disintegrant included in a foamed immediate release system composed of a polymer excipient and an Active Pharmaceutical Ingredient (API). Indomethacin (INM) is used as model API; Eudragit® EPO (EPO) is used as polymer excipient; AcDiSol and Crospovidone (Cros) are used as two kinds of disintegrant. The main objectives are to gain an understanding of the resulting morphologies, as well as the impact of disintegrants on drug release from foamed polymeric matrices.

In the first part of this research, the Hot Melt Extrusion (HME) process is used to compound the following pharmaceutical formulations: …

Hydrodynamic Effects Of A Cannula In A Usp Dissolution Testing Apparatus 2, Qianqian Liu

Theses

Dissolution testing is routinely used in the pharmaceutical industry to provide in vitro drug release information for drug development and quality control purposes. The USP Testing Apparatus 2 is the most common dissolution testing system for solid dosage forms. Usually, sampling cannulas are used to take samples manually from the dissolution medium. However, the inserted cannula can alter the normal fluid flow within the vessel and produce different dissolution testing results.

The hydrodynamic effects introduced by a permanently inserted cannula in a USP Dissolution Testing Apparatus 2 were evaluated by two approaches. Firstly, the dissolution tests were conducted with two …

Heterogeneous Combustion Of Condensed Particles In Transition Regime, Deniz Yildiz

Theses

A steady-state model of heterogeneous combustion for a spherical particle is developed accounting for the transition regime of heat and mass transfer. The model assumes formation of condensed products and reaction rate controlled by the transport of oxidizer to the particle surface. The model is based on the Fuchs’ limiting sphere approach. Calculations are performed for combustion of zirconium particles of different sizes. Temperature and oxygen concentration profiles are calculated and compared to those predicted by the continuous medium transfer model. It is shown that for particles in the range from 100 nm up to 30 gm heat and mass …

Effect Of Tablet Compression On The Dissolution Of Aspirin Tablets Using A Novel Off-Center Paddle Impeller (Opi) Dissolution Testing System, Chuan Sun

Theses

In the pharmaceutical industry, dissolution testing is routinely carried out to determine the dissolution rate of oral solid dosage forms. Among several testing devices, the USP Dissolution Apparatus 2 is the device most commonly used. However, despite its widespread use, this apparatus has been shown to produce test failures and to be very sensitive to a number of small geometry changes.

The objective of this study was to determine whether a novel dissolution system termed “OPI” for “off-center paddle impeller” was sensitive enough to determine differences in tablet dissolution profiles caused by different compression pressure during the tablet manufacturing process. …

Methane Partial Oxidation Over Phthalocyanine Catalyst, Yuan Zhu

Theses

The partial oxidation reaction of methane over a zeolite-supported ruthenium phthalocyanine catalyst is studied in a packed bed reactor. The investigation of such reaction is desirable because partial oxidation of methane yields a synthesis gas that can be upgraded to liquid chemicals and fuels.

Reactants of this study are He-diluted CH₄ and O₂. The effluent includes unreacted CH₄ and O₂, He, CO, CO₂, H₂, and H₂O vapor. Thermal conductivity gas chromatography is applied to identify the mole fractions of reactants and products. System pressure is maintained at 50 …

Production Of Stable Bcs Class Ii Drug Suspensions By Melt Emulsification And Subsequent Incorporation Into Polymer Strip Films, Emanuel Joseph Vizzotti

Theses

One of the ways to improve the dissolution rate of poorly water-soluble drugs is to produce fine drug particles with increased surface area. This increase will lead to bioavailability enhancement. However, smaller drug particles are thermodynamically unstable and tend to aggregate or grow. Therefore, proper formulation and process parameters must be chosen to keep the particles small. In this study, fine drug particles of two model drugs, fenofibrate and ibuprofen, are prepared by the melt emulsification technique. The influence of suspension formulation (i.e., the inclusion of polymers and surface-active agents) on particle stability is investigated. Moreover, different agitation techniques during …

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 …

Hollow Fiber Membrane-Based Air Gap Membrane Distillation, Xuan Wang

Theses

Membrane Distillation (MD) is a thermally-driven separation process. In this research, desalination of 1 % NaCl solution is achieved by one type of MD namely, Air Gap Membrane Distillation (AGMD). The characteristics of AGMD are evaluated by using a hollow-fiber-set-based compact device. Hot brine solution and cold water are passed through two different fiber sets separately: porous hydrophobic polyvinylidene fluoride hollow fibers of the E type (PVDF E) and solid polypropylene (PP) hollow fibers. Vapor from the hot brine crosses the membrane pores of the PVDF fibers and the air gap, and finally condenses over the surface of solid hollow …

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 …

Dissolution Of Different Commercial Aspirin Tablets Using A Novel Off-Center Paddle Impeller (Opi) Dissolution Testing System, Yang Qu

Theses

Dissolution testing is routinely conducted in the pharmaceutical industry to provide in vitro drug release information for quality control purposes. The most common dissolution testing system for solid dosage forms is the United States Pharmacopeia (USP) Dissolution Testing Apparatus 2. In this work, a modified Apparatus 2, termed "OPI" System for "off-center paddle impeller," in which the impeller is placed 8 mm off center in the vessel is tested to determine its sensitivity to differentiate between the dissolution profiles of differently formulated and manufactured tablets. Dissolution tests are conducted with both the OPI System and the Standard System using three …

Effects Of Api Particle Size On The Dissolution Rate In Molten Polymer Excipient Matrices During Hot Melt Extrusion, Conducted In A Co-Rotating Twin-Screw Extruder, Meng Li

Theses

The effect of the Active Pharmaceutical Ingredient (API) particle size on the dissolution rate in the polymer excipient during hot melt extrusion is investigated using a co-rotating twin-screw extruder with three different screw configurations. Acetaminophen (APAP) and amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCap-PVAc-PEG) (Soluplus) are chosen as the model API and water- soluble polymer excipient, respectively. APAP is milled using a fluid energy mill (FEM) into two different particle sizes. The thermal properties of processed samples are characterized by TGA and DSC. SEM and optical microscopy are also used in the morphological studies. Under quiescent conditions, API particles …

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 …