The effect of concentration, vehicle and surfactant on the
absorption of benzocaine -³H across the rat's rectal mucosa was
investigated. Blood radioactivity levels were determined after the
application of benzociane -³H containing suppositories and ointments.
A wet oxidation method was used for sample digestion. Since the
radioactivity counted is the...
The stability of 1 3-bis(2-chloroethyl)-1-nitrosourea
(NSC 409962)(BCNU) was investigated in several buffered
aqueous media, in mixed solvent and in nonaqueous solvent
systems, and in the presence of several electrolytes and
nonelectrolytes. The degradation rate constant of BCNU in
these systems was calculated from the parameters of the
linear regression of...
The bioavailability and pharmacokinetics of theophylline
in rabbits were determined following both oral and
intravenous administration of the drug. Serum theophylline
concentrations were determined using high pressure
liquid chromatography. Pharmacokinetic parameters were
determined and verified by computer analysis. The overall
mean Beta disposition constant was 0.089 hr⁻¹ which corresponds
to...
Dyphylline is an analog of theophylline and the latter
is the most popular member of the methylxanthine family in
use for the treatment of asthma. Although dyphylline is
devoid of some problems associated with theophylline, a
reported short half-life has made it's clinical usefulness
limited. To avoid this problem a...
Improved assay methods for determination of dyphylline levels in plasma, saliva, and urine utilizing high pressure liquid chromatography have been developed. Detection of levels as low as 25 ng/ml from 0.5 ml plasma and 50 ng/ml from 0.5 ml saliva were possible. Both procedures utilized the same extraction process. A...
The role of iron in the body is well known for it is a component of hemoglobin, myoglobin, cytochrome, enzyme catalase and peroxidase. Iron deficiency anemia is widespread among vulnerable groups in industrialized societies and in the general population of tropical developing areas. In the United States there are ten...
The relative bioavailability and pharmacodynamics
of tolbutamide from two different commercially available
tablet products has been evaluated in healthy subjects
in a single dose cross over study. Products were aged
by exposing tablets to 98% relative humidity for 3 days
at ambient temperature which was found to differentially
affect both...
Dyphylline is an analogue of theophylline and the
latter is the most popular member of the methyixanthine
family in use for the treatment of asthma. Although
dyphylline is devoid of some problems associated with
theophylline, a reported short half-life for dyphylline
(2.1 hours) has made its clinical usefulness limited. In...
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...
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....
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...
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...
Gastric retention time of single unit dosage forms in swine was found
to be much longer than in humans. It was concluded that swine are not a
good animal model to study GI transit time of nonerodable or slowly eroded
dosage forms. Noneradable and slowly eroded dosage forms used to...
Lactobacilli have been used in the dairy and pharmaceutical industries because of their nutritious and/or
therapeutic effects. Lactobacillus acidophilus and
Lactobacillus bulqaricus were isolated from a commercially
available product and studied for their growth and colony
characteristics as described in Chapter I and Chapter II.
Survival of these lactobacilli in...
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...
Effects of lactobacilli in enteric coated capsules
were studied in piglets (Chapter I). Lactobacillus
acidophilus and Lactobacillus bulgaricus isolated from a
commercial product were formulated in capsules, enteric
coated, and then given to both Escherichia coli-challenged
and unchallenged baby pigs. Decreased
incidence and severity of diarrhea, and decreased weight
deceleration...
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...
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...
In vivo research following ingesting of commercially available
Lactobacillus tablets, which contain about 2X10⁶ cfu/tablet of
Lactobacillus acidophilus and Lactobacillus bulgaricus cells in a dose
of four tablets daily, showed serum lipoprotein concentrations did not
change significantly. In order to increase the number of viable
Lactobacillus bacteria after challenging in...
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...
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...
This thesis describes a project to produce controlled release ketoprofen beads for capsules, both at Oregon State University and in an industrial scale-up operation, that are bioequivalent to the commercial product Oruvail. A bead formulation was produced by layering drug and binders in water onto nonpareil sugar seeds in a...
This thesis describes a novel "Tablet-in-a-Bottle" oral suspension formulation.
Ingredients with unstable physical or chemical characteristics can be placed in a core tablet, and then dry compression coated with an outer layer which provides separation from other components. The new suspension formulation comprises fast disintegrating clavulanic acid (KCA) tablets with...
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...
Acetaminophen has been safely used for analgesia for many years.
Literature suggests that a plasma acetaminophen level of 5μg/ml is necessary to
maintain analgesic relief in humans. Current dosing regiments are inconvenient (every
4-6 hours) and do not maintain this minimum plasma level. Simulations were
conducted to examine various doses...
This thesis is compromised of two distinct formulation sections, which are described below:
New compression-coated tablet formulations were developed for amoxicillin/clavulanate. Amoxicillin in an outer coat was separated from clavulanic acid in a core tablet by inactive ingredients in a middle coat. A chewable compression-coated tablet formulation with 50% stearic...
This dissertation describes formulation of a gastric retention device (GRD) and sustained release (SR) hydrochlorothiazide beads at Oregon State University. Formulation condition and amounts of excipients had significant influence on characteristic of the GRD. The GRD containing SR hydrochlorothiazide beads was employed to assess bioavailability/bioequivalency study in healthy subjects. An...
This dissertation is comprised of four distinct formulation sections, which are described below: A novel solid dosage formulation was investigated for achieving zero-order drug release profile by combining tablet shape design and tablet membrane film coating. Verapmail (model drug) was compressed into hydrophilic matrix tablet cores of flat-faced and bi-convex...
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...
This thesis describes in vitro and in vivo evaluation of a gastric retention formulation (GRF) developed at Oregon State University. The formulation was prepared from xanthan gum and locust bean gum as gelling agents and other formulation ingredients were added, then it was originally vacuum oven dried. The effect of...
This thesis describes evaluation of a gastric retention device (GRD) developed at Oregon State University. The device was originally fabricated from Xanthan gum and Locust bean gum. A modified gastric retention device containing other additives was developed and investigated in this work. The modified device was evaluated in vitro for...
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....
Effects of gastrointestinal transit on plasma concentrations of drugs from enteric-coated pellet formulations were demonstrated using pharmacokinetic models describing plasma concentrations of drugs from various enteric-coated pellet formulations. Gastric emptying time, lag time of emptying, and drug release rate from pellets in the small intestine, along with other pharmacokinetic parameters...
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...
Hot-melt pan-coating, which is a novel coating method and takes 2-3 hours for 300 mg coating weight gain per capsule and tamper-resistant coating, which takes 30 minutes, is much faster than tedious sugar coating and allows greater coating weight gains in shorter times than spray-melt coating. Although hot-melt pan coating...
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...
A nifedipine sustained release dosage form was prepared by using hot-melt batch
coating. Substrates are sugar beads, mesh size 30-35. Stearic acid, Acid Triglyceride, and
carnauba wax were coating agents used to make single layer coated beads and multiple
layer coated beads containing nifedipine. Dissolution of nifedipine from the beads...
The first project of this thesis is an in vitro study. This study was performed with 8 hydrocortisone topical products on the market for the purpose of comparing one Tec Lab product, a Corticool gel, to the other seven common products on the market. The permeation of these products was...
Vital rates and population connectivity are fundamental concepts in animal ecology and such information is critical for successful conservation planning. The Black-backed Woodpecker (Picoides arcticus) is a species of conservation concern because of its strong association with forests recently burned by high-severity wildfire. However, several recent studies have found that...
Bee populations are declining around the globe, while the need for their pollination services is increasing with growing food demands by an expanding population. There is a need for innovative practices to increase pollination in agricultural environments without harming wild bee populations. However, the use of artificial visual attractants has...
Effective watershed restoration planning and prioritization is often very difficult because decision making typically involves a large number of alternatives evaluated on the basis of multiple and often conflicting technical, social, economic, and environmental objectives and criteria. In order to solve such complex decision making problems, multiobjective decision making (MODM)...