The microbial contamination rate was compared for parenteral nutrition solutions prepared by patients for home use and by pharmacy personnel for inpatient use. The methodology was divided into three phases. Phase I validated the Ivex[superscript R]-2 0.22 micron inline filter as a tool for microbiological testing in 5% dextrose injections....
It has been standard practice in the United States to separate lipid emulsions from the other components of total parenteral nutrition due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent...
The stability of valproate sodium syrup repackaged in three types of unit dose containers was studied. Two-milliliter samples of commercial valproate sodium syrup 250 mg/5 ml (of valproic acid) were packaged in polypropylene oral syringes, glass oral syringes, and glass vials (126 of each type). These were stored at 4,...
Two specific goals were addressed for this dissertation. First to investigate and identify the mechanistic profile of ketoconazole (KT)-induced hepatotoxicity by utilizing in vivo and in vitro approaches determining the mechanism of action for the hepatotoxicity incurred. To date, there has not been a mechanistic determination of the hepatotoxicity associated...
Development of a novel, useful, orally administered dosage form
providing controlled, sustained release of an active ingredient was desired.
Film layers of Aquacoat and Eudragit L-30D (commercially available
coating materials) were applied to acetaminophen cores. Amount of coating
material, number of polymer layers, and order of application were varied.
In...
Male Sprague Dawley rats received a single intraperitoneal dose
of BCNU in experiments designed to measure biochemical changes associated with the pulmonary toxicity described for this agent. Changes in
serum and lung lavage angiotensin converting enzyme (ACE) activity
were measured to detect changes in pulmonary endothelial cell integrity. Alpha-1-proteinase inhibitor...
This dissertation describes the development of a new sustained release formulation of nifedipine. The new formulation was developed by coating commercially available immediate release soft elastic gelatin capsules using a spray coating technique with two different polymeric combinations. Dissolution studies were conducted and showed that controlled release of nifedipine was...
The sea offers a wide variety of potentially useful resources. Marine algae have been a rich source of structurally unique natural products showing diverse biological properties. The current need to develop new antifungal, antibiotic, anticancer and antiviral drugs has prompted intense research efforts into the discovery, isolation and structure determination...
Currently, the only anthrax vaccine licensed for human use in the United States is the Anthrax-vaccine-absorbed (AVA or Biothrax®). AVA suffers from several drawbacks, including a complicated and lengthy dosing schedule that requires six initial injections administered over eighteen months, followed by annual boosters. Therefore, a new generation anthrax vaccine...
This thesis details my investigation of some pharmaceuticals and natural products on the transport of drugs which are substrates of P-glycoprotein (P-gp), such as cyclosporin A (CSA) and digoxin by using Caco-2 and MDCKII-MDR1 drug transport models. Three objectives were performed to address this goal. The first objective was to...
Pharmacokinetics of theophylline and N-7 substituted
theophylline in rabbits when administered alone and in
various combinations were investigated. This thesis has
four chapters dealing with etophylline and theophylline;
proxyphylline and theophylline; dyphylline and theophylline;
and etophylline, proxyphylline and dyphylline pharmacokinetics
when administered concomitantly. All chapters
are interrelated. Each chapter has...
Four different treatments of acetaminophen were administered to
eight healthy volunteers in multiple doses (five doses). Saliva
acetaminophen concentration-time profiles were determined. Non-compartmental
pharmacokinetic parameters for the first and last dose
were calculated and compared to determine whether acetaminophen
exhibited linear or dose dependent pharmacokinetics. Dose corrected
area under the...
The thrust of this thesis is to study oral solid dosage formulation using hot melt coating method and to use pharmacokinetic modeling and simulation (PK M&S) as a tool that can help to predict pharmacokinetics of a drug in human and the probability of passing various bioequivalence criteria of the...
A study was designed to examine the pharmacokinetics of theophylline in a well defined group of congestive heart failure (CHF) patients, without liver disease, and to evaluate the validity of the dosage guidelines recommended by the FDA. A total of five CHF patients and seven non-CHF patients were entered and...
A two-part study was conducted with three poorly water soluble
drugs (phenylbutazone, tolbutamide, theophylline) to develop two new
drug delivery systems based on physical-chemical approaches.
In the first part, tolbutamide and phenylbutazone were made into
solid dispersions with various excipients using a lyophilization
technique. In vitro dissolution studies of these...
This thesis is an investigation of the natural products deriving from marine algae and cyanobacteria and has resulted in the discovery of eleven new secondary metabolites. The structure elucidations of these new molecules were performed using a variety of spectroscopic techniques. Four new macrolides were isolated and characterized from the...
Dyphylline has been shown to be rapidly and completely
absorbed from oral tablets in an absolute bioavailability
study. In a pilot study two healthy male subjects received
1000 mg of dyphylline via intravenous infuson at a rate of
50 mg/min (1.0 ml/min) for 20 minutes. Plasma samples were
collected for...
The chemical stability of folic acid in 25 percent dextrose,
3.5 percent amino acids and multivitamin solution was investigated.
Solutions of 2.5, 5.0, 7.5 and 1.0 mg/liter of folic acid admixed
in the study solution were prepared. Solutions were stored
in light-room temperature, light-refrigeration, dark-room temperature,
or dark-refrigeration. Samples were...
This thesis details my investigations of marine cyanobacterial natural products that resulted in the discovery of eighteen new secondary metabolites. Isolation and characterization of these unique molecules were carried out using different chromatographic techniques and by careful analyses of 1D and 2D NMR data, respectively. Preliminary bioassays of the crude...
This thesis is an account of investigation on the natural products deriving from various marine algae and has resulted in the discovery of eleven novel bioactive metabolites. Isolation and characterization of these new molecules were carried out using different chromatographic techniques and by analyses of different spectroscopic data, respectively. Using...
An oral Vibrio vaccine for salmonids was developed.
The vaccine was produced by spray coating lyophilized
formalin-killed whole cells of Vibrio anguillarum (VA LS 1-
74) onto non-pareil sugar beads. Then methacrylic acrylic
acid copolymer (Eudragit L-30D) was applied as an enteric
protective coating.
Using x-ray radiographic techniques, it was...
A high-pressure liquid chromatography method based on
reported literature was developed for the quantitative
analysis of chlorpheniramine, pseudoephedrine,
phenylpropanolamine and acetaminophen in dissolution
fluids and urine. The effects of buffer, pH and different
concentrations of organic solvent in the mobile phase on
chromatographic separation are described in Chapter I.
Dissolution...
Perennial ryegrass (PRG, Lolium perenne) is a hardy cool-season grass that is infected with the endophytic fungus Neotyphodium lolii, which enables the plant to be insect repellant and drought resistant, lowering the use of insecticides and fertilizers. However, this fungus produces the compound lolitrem B (LB, m/z 686.4) which causes...
This thesis describes the chemical investigation of marine cyanobacteria collected in Madagascar and Panama with an emphasis on the isolation and structure elucidation of medicinally relevant secondary metabolites.
A collection of the marine cyanobacterium Lyngbya majuscula from the Radames Islands, Madagascar yielded two new cyclic depsipeptides, radamamides A and B,...
Gastrointestinal (GI) transit data were collected using pigs
as animal models. Density and size effects of non-disintegrating
dosage forms on GI transit were investigated. Total GI transit
times range from 2 to 33 days for 22 administrations of these nondisintegrating
dosage forms. Pigs are found to not be an
appropriate...
Poor aqueous solubility of a large number of newly discovered chemical entities is posing a significant challenge for the formulation industry and is delaying their drug development. The number of formulation techniques available to solubilize these poorly soluble molecules is very limited. In addition to that, traditional formulation methods involve...
This thesis describes 1) development of a gastric retention device (GRD) to
increase gastric retention time of certain drugs, 2) product formulations of an immediate
release itraconazole and controlled-release ketoprofen. GRD was fabricated from crosslinked
carbohydrate polymers. Rate and extent of hydration of the film in water and in
simulated...
Cardiac A₁ adenosine receptors mediate cardioinhibitory
properties of adenosine and structural congeners. The objective of
these studies was to increase our understanding of molecular
processes involved in ligand interactions with receptors mediating
cardioinhibitory effects of adenosine and the interactions of these
receptors with guanine nucleotide binding regulatory proteins.
Porcine atrial...
This dissertation presents a research series demonstrating the use of pharmacokinetic modeling and simulations as tools to assess drug concentration and disposition in patient populations. For drugs requiring therapeutic drug monitoring, these tools are necessary to ensure patients are receiving a safe and effective dose of medication to address their...
This thesis describes investigations of marine algal secondary metabolites, with particular interest in their biomedical and agrichemical potential. Invaluable in such pursuits have been the access and application of advanced spectroscopic techniques, such as NMR, and the ability to assess the biological activity of the algal samples in a variety...
Following surveys of seaweeds in Oregon and the Caribbean, four algal species were selected for study on the basis of their crude extract biological activity or thin-layer chromatographic characteristics. Extracts were fractionated by normal phase chromatography, including high performance liquid chromatography (HPLC). Derivatives (methyl esters, acetates, and benzoates) of natural...
Oral administration is the most practical way of vaccination of fish. It has advantages over intraperitoneal injection and immersion methods that include no stressful handling, no interference with routine fish husbandry and antigens can be delivered to the fish in their feed.
An oral antigen delivery system was developed for...
Product formulation and in vitro dissolution characteristics of sustained-release chewable tablet dosage
forms are presented in chapter one of this thesis. In vivo
single dose and multiple dose studies of two
sustained-release formulations as well as one conventional
dyphylline formulation are described in chapter two. The
pharmacokinetics of dyphylline following...
This dissertation describes how to apply pharmacokinetic simulations and modeling in a clinical setting to monitor and adjust drug dosing in special patient populations. Pharmacokinetic simulations were used to investigate efficacy and risk of drug toxicity of a new dosing regimen for aminoglycoside antibiotics when administered to renal failure patients....
I have participated in a drug discovery program designed to screen marine algae for
inhibitors of cancer-related enzymes, antitumor compounds, antiinflammatory substances,
and other agents of potential pharmaceutical utility. Over 1,500 lipid and aqueous extracts
of marine plants and animals were surveyed for biomedical potential. Assays designed to
screen extracts...
Propionic acid, live Propionibacterium shermanii, and
Dimethyl Fumarate (DMF) were tested for their stimulatory or
inhibitory efects on yeast, bacteria, and molds. The amount
of propionic acid required for inhibition of molds was
strain specific and equal to or less than that required for
inhibition of the yeasts. Live P....
This thesis describes evaluation of a novel self-sealing chewable sustained release tablet that can maintain controlled release of drug regardless of compaction, crushing, or chewing. The new formulation contains polyethylene oxide which produces a sealant effect for cracks produced in the polymer coating during compaction. Dissolution studies were conducted and...
Cells of the ventrolateral dermomyotome delaminate and migrate into the limb buds where they give rise to all muscles of the limbs. The migratory cells proliferate and form myoblasts, which withdraw from the cell cycle to become terminally differentiated myocytes. The regulatory mechanisms that control the later steps of this...
Pharmacokinetic parameters for theophylline and
dyphylline were evaluated in horse cerebrospinal fluid
(csf) and plasma. Pharmacokinetic parameters did not
differ significantly (p > 0.05) at the same dose for
either drug when administered alone or concomitantly.
Theophylline and dyphylline penetrate horse csf to
produce approximately 1/2 the concentrations found in...