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Biomedical subjects

T J Roseman

Publications and source records attributed to T J Roseman.

At least 19 recordsLinked to original sources
PubMed1990

In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model.

The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).

Animals↗
PubMed1990

The development of USP dissolution and drug release standards.

Dissolution tests have been in use in the pharmaceutical industry for over 20 years, and they are official in The United States Pharmacopeia since the early 1960s. The dissolution test, reviewed primarily as a quality control tool, replaced the use of disintegration tests which had been official in The United States Pharmacopeia since 1950. Refinements in the dissolution test equipment and methodology have occurred over the years in order to enhance its relevance. The Subcommittees of the USP Committee of Revision dealing with these issues have developed and refined compendial dissolution standards and policies for conventional solid-oral dosage forms and modified-release dosage forms.

Delayed-Action Preparations↗
PubMed1984

Menses induction in rhesus monkeys using a controlled-release vaginal delivery system containing (15S) 15-methyl prostaglandin F2 alpha methyl ester.

Polymeric controlled-release vaginal delivery systems were designed for (15S)15-methyl prostaglandin (PG)F2 alpha methyl ester (carboprost methyl). The drug was incorporated into a highly permeable reservoir membrane that was bound to a relatively nonpermeable support membrane. The rate of drug release was controlled by coating the reservoir membrane with a less permeable rate-controlling membrane. Vaginal devices were prepared with in vitro steady-state release rates from 5 to 180 microgram/hour. The release curves were characterized by an initial, transient rapid release of the drug, followed by a linear zero-order release phase. Pregnancy was terminated in rhesus monkeys following a 24-hour treatment with vaginal devices having release rates of carboprost methyl of 45 microgram/hour or greater. Successful menses induction was associated with peripheral plasma concentrations of (15S)15-methyl PGF2 alpha between 2000 and 3000 pg/ml. Peripheral plasma concentrations of progesterone declined very rapidly to less than 1.0 ng/ml in monkeys in which pregnancy was terminated. These studies demonstrate the feasibility of manufacturing controlled-release vaginal delivery systems containing carboprost methyl for use in early pregnancy termination.

Abortion, Induced↗
PubMed1983

Solubility and partitioning VI: octanol solubility and octanol-water partition coefficients.

A simple equation for the estimation of the aqueous solubility of crystalline solutes was previously derived based on the assumption that the presence of water does not significantly alter the crystal properties of the solute. The data presented verify the solubility equation for a set of 36 nonelectrolytes and weak electrolytes. Using the same set of solutes, the two major assumptions used to derive the equation were also verified: that the octanol solubility of nonelectrolytes is exponentially proportional to the melting point of the solute and that the octanol-water solubility ratio is a good approximation of the octanol-water partition coefficient.

Chemical Phenomena↗
PubMed1983

Menses induction and second-trimester pregnancy termination using a polymeric controlled release vaginal delivery system containing (15S)15-methyl PGF2 alpha methyl ester.

A polymeric controlled release vaginal delivery system was developed for 15(S)15-methyl PGF2 alpha methyl ester. This delivery system is a reservoir-type device consisting of laminated membranes that are mounted on an inert holder. The delivery systems were designed to have in vitro steady-state release rates of 50 or 100 micrograms/hr. Included in the study were seven early pregnant (amenorrhea up to 49 days) patients who were treated with 50 micrograms/hr devices and five early pregnant patients who were treated with 100 micrograms/hr devices. Three second-trimester cases received a 50 micrograms/hr device and five received a 100 micrograms/hr device. Five of the seven early first-trimester patients given 50 micrograms/hr devices aborted completely. The plasma levels of PG in those patients were 400-600 pg/ml for up to 6 hours. In the two cases that did not abort completely, the plasma levels of drug dropped sharply after both patients had started to bleed vaginally one hour after administration of the device. All five early pregnant patients treated with 100 micrograms/hr devices aborted completely. None of the three second-trimester cases aborted within 24 hours following administration of the 50 micrograms/hr devices. Three of the five second-trimester patients aborted within 24 hours following treatment with 100 micrograms/hr devices. The plasma levels of drug reached 1-1.5 ng/ml during the first 2-5 hours and then declined, especially after rupture of the membranes. The variation of plasma levels of drug following vaginal administration of the devices in different individuals was considerably less than following vaginal suppositories. Therefore, this device seems to be close to an ideal delivery system for vaginal administration of abortifacients.

Abortifacient Agents↗
PubMed1981

Solubility and partitioning IV: Aqueous solubility and octanol-water partition coefficients of liquid nonelectrolytes.

The aqueous solubility and octanol-water partition coefficient of over 100 nonelectrolyte organic liquid solutes are related by the simple equation log Sw = -1.016 log PC +0.515, where Sw is the molar solubility of liquid solutes in water and PC is the experimental partition coefficient of the solutes in the octanol-water system. The liquids studied represent a wide variety of organic compounds including aliphatic and aromatic hydrocarbons, alcohols, esters, ethers, aldehydes, and ketones. This finding is in agreement with that reported by Hansch and coworkers. However, these results are significant because only the experimental values for the aqueous solubilities and octanol-water partition coefficients are included, as opposed to the calculated partition coefficients used by Hansch. This relationship is extremely useful in understanding the overall solubility and partitioning phenomenon for organic liquids are provides a basis for studying crystalline solids and gases.

Chemical Phenomena↗
PubMed1981

Transport of prostaglandins through silicone rubber.

The in vitro release profiles of the F-series of prostaglandins were determined from a silicone rubber matrix of constant surface area. Silicone rubber was selective toward prostaglandin transport and offers potential as a controlled-release delivery system. Drug release patterns were dependent on the lipophilicity of the prostaglandin molecule. For dinoprost (prostaglandin F2 alpha), the following sequences was observed: methyl ester greater than free acid greater than tromethamine salt. The biologically potent carboprost methyl [(15S)-15-methylprostaglandin F2 alpha methyl ester] was release considerably faster than the methyl ester of the parent dinoprost molecule, while release of the tromethamine salt of the two prostaglandins was similar. Permeability rates of the salts were depressed substantially when compared to their respective C-1 methyl esters. Results from independent membrane transport studies supported the observed dependence of steady-state flux on the chemical structure of the prostaglandin molecule. Plots of the amount released per unit area versus the square root of time were linear except for the initial drug release phase, and the total amount of prostaglandin released increased as the initial loading dose was raised. The data were analyzed according to a physical model describing drug release from inert matrix systems. The observed concentration dependence was consistent with the predictions of the model.

Diffusion↗
PubMed1981

Continuous flow bead-bed dissolution apparatus for suppositories.

A bead-bed dissolution apparatus for suppositories was evaluated by measuring the release of benzocaine from various vehicles. During dissolution, suppositories soften, deform, disintegrate, and eventually pass through a phase change from a solid to an oil. The control of the interfacial area during dissolution is a key factor in obtaining experimentally reproducible release data. The proposed suppository dissolution apparatus was designed to provide greater constancy of the exposed suppository area for dissolution. The apparatus consisted of a glass bead-bed containing the suppository. A continuous flow of liquid was passed through the bead-bed at a constant rate. Direct contact of the suppository was maintained with the dissolution medium, confining the suppository within the beads.

Benzocaine↗
PubMed1979

Stability of E-type prostaglandins in triacetin.

A drug delivery system for E-type prostaglandins is described. In this system, consisting of drug dissolved in triacetin and filled into soft gelatin capsules, normally unstable prostaglandins show excellent stability at room temperature.

Drug Stability↗
PubMed1979

Lyophilization of pharmaceutical injections: theoretical physical model.

A physical model for the lyophilization kinetics of parenteral formulations is presented. Mathematical relationships are derived, which involve the simultaneous change in the receding boundary of the ice-vapor interface with time as well as water vapor diffusion across the dry porous matrix and boundary layer. Heat from an external heat source is transferred across the frozen solution to the receding ice surface. The model predicts that the water lost and the receding boundary distance are linearly related to the square root of time when lyophilization is matrix controlled. The mathematical descriptions are predictive of the physicochemical and transport events and can lead to the design of quantitative experiments to relate theory to formulation design.

Chemical Phenomena↗
PubMed1976

Glass for parenteral products: a surface view using the scanning electron microscope.

The scanning electron microscope was utilized to explore the internal surface of glass ampuls and vials used in parenteral products. The surface topography of USP Type I borosilicate glass containers was viewed after exposure to "sulfur," ammonium bifluoride, and sulfuric acid treatments. The scanning electron micrographs showed startling differences in the appearance of the surface regions. "Sulfur treatment" of ampuls was associated with a pitting of the surface and the presence of sodium sulfate crystals. The sulfur treatment of vials altered the glass surface in a characteristically different manner. The dissimilarity between the surface appearances was attributed to the method of sulfur treatment. Ampuls exposed to sulfuric acid solutions at room temperature did not show the pitting associated with the sulfur treatment. Scanning electron micrographs of ammonium bifluoride-treated ampuls showed a relief effect, suggesting that the glass was affected by the bifluoride solution but that sufficient stripping of the surface layer did not occur to remove the pits associated with the sulfur treatment. Flakes emanating from the glass were identified with the aid of the electron microprobe. Scanning electron micrographs showed that these vitreous flakes resulted from a delamination of a thin layer of the glass surface. It is concluded that the scanning electron microscope, in conjunction with other analytical techniques, is a valuable tool in assessing the quality of glass used for parenteral products. The techniques studied should be of particular importance to the pharmaceutical industry where efforts are being made to reduce the levels of particulate matter in parenteral dosage forms.

Beryllium↗
PubMed1976

High-pressure liquid chromatographic determination of the 15-epimer of dinoprost in bulk drug.

The p-nitrophenacyl esters of dinoprost and its 15-epimer are well resolved using high-pressure liquid chromatography. Quantitation was achieved using the internal standard technique. The specially synthesized diphenylurea ester of cholic acid was found to be a model internal standard. Graphs of peak height ratios of the prostaglandin to the internal standard were linear with respect to the amount of prostaglandin injected, with the lower detection limit of the 15-epimer being about 0.5%. Data are presented that demonstrate the usefulness of this analytical technique in determining the concentration of the 15-epimer present during studies on the kinetics of decomposition of dinoprost.

Chromatography, High Pressure Liquid↗
PubMed1976

Effect of vaginally administered 15(S)15-methyl-PGF2alpha on egg transport and fertility in rabbits.

The effects of vaginal suppositories containing 1.0 mg of 15[S]15-methy-PGF2alpha on oviductal motility, egg transport, and fertility were determined in rabbits. Suppository treatment caused a significant increase (P less than 0.02) in the amplitude of oviductal contractions, and a decrease in the frequency of contractractions (P less than 0.04). Altered oviductal motility persisted for an average of 2 hr after treatment. Treatment with 1, 2, or 3 suppositories at various times after ovulation caused a significant reduction in the number of eggs located in the oviducts (P less than 0.025). There was, however, a great deal of variation in egg recovery in treated animals (range 0 to 100%). Treatment of mated rabbits during the time of tubal egg transport caused a significant reduction in the number of Day-12 implants (P less than 0.05). The percentage of corpora lutea represented by Day-12 implants was similar to egg recovery rates in animals similarly treated. The treatment had no effect on fetal survival from Day 12 to 28 of pregnancy. The decrease in fertility caused by these vaginal suppositories is presumably due to the stimulatory effect on oviductal motility which accelerates tubal transport of the embryos into the uterus. Embryos that arrive in the uterus prematurely probably do not implant and degenerate or are expelled.

Animals↗
PubMed1976

Evaluation of vaginal delivery systems containing 15[s]15-methyl PGF2alpha methyl ester.

Silicone vaginal delivery systems containing 15[S]15-methyl-PGF2alpha methyl ester have been evaluated in vitro, and in vivo in the rhesus monkey. Three types of vaginal devices have been formulated to contain different concentrations of drug. The cumulative amount of 15[s]15-methyl-PGF2alpha methyl ester released in vitro from a planar silicone rubber matrix was dependent upon the initial loading dose of the prostaglandin. Drug-containing vaginal rings were evaluated in early pregnant and mid-trimester pregnant monkeys. Within 10 min after ring administration there was an increase in the amplitude and frequency of contractions. In mid-trimester pregnant animals there was an initial increase in plasma progesterone and then a decrease following treatment, while there was a progressive decrease in plasma progesterone in early pregnant animals. All 6 mid-trimester pregnant monkeys treated with vaginal rings aborted. Pregnancy was terminated in 4 of 5 early pregnant monkeys treated with vaginal rings. Blood levels of 15-methyl-PGF2alpha rose rapidly to attain a peak 1 hr after treatment with vaginal rings. After the peak, plasma levels of 15-methul-PGF2alpha declined to a plateau which was fairly constant between 2 and 8 hr. Vaginal silicone-gelatin laminates containing 15[s]15-methyl-PGF2alpha methyl ester were also effective in causing an increase in uterine muscle activity and terminating pregnancy in mid-trimester in pregnant monkeys. Plasma progesterone also increased shortly after treatment in these animals, and then declined after the peak at 8 hr. The plasma profile of 15-methyl-PGF2alpha when animals were treated with these vaginal laminates was different from that observed following ring treatment. In pregnant animals the concentration of 15-methyl-PGF2alpha rose more slowly following laminate insertion, and the peak values were considerably less than those following ring treatment. Vaginal devices used in monkeys and humans caused plasma concentrations of 15-methyl-PGF2alpha that were generally lower than those observed in monkeys treated with either vaginal rings or laminates. These studies have demonstrated that silicone vaginal delivery systems containing 15[S]15-methyl-PGF2alpha methyl ester result in sustained and fairly constant plasma levels of 15-methyl-PGF2alpha, and terminate both 1st- and 2nd-trimester pregnancies in the monkey. The vaginal device offers the possibility for self-administration of PGs for early pregnancy termination and menstrual cycle regulation.

Abortion, Induced↗