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Biomedical subjects

H W Jun

Publications and source records attributed to H W Jun.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effectiveness and mode of action of isopropyl myristate as a permeation enhancer for naproxen through shed snake skin.

The effectiveness and mode of action of isopropyl myristate (IPM) as an enhancer for the permeation of naproxen through shed snake skin have been investigated. The highest naproxen permeability was afforded by IPM (36.2 x 10(-4) cm h-1), followed by menthol (25.0 x 10(-4) cm h-1), oleic acid (11.1 x 10(-4) cm h-1), azone (7.3 x 10(-4) cm h-1) and control (1.4 x 10(-4) cm h-1). Whereas the permeability of un-ionized naproxen (47.4 x 10(-5) cm h-1) was much greater than that of ionized naproxen (1.11 x 10(-5) cm h-1), IPM-treatment of the intact skin increased the flux of ionized naproxen significantly more (50-fold) than that of un-ionized naproxen (15-fold). The large effect of pH on the permeation of naproxen through the intact stratum corneum became insignificant after extraction of lipids from the skin. Similar permeation of naproxen through intact and delipidized skin after IPM treatment indicated that the lipid barrier of the skin was largely impaired by IPM. Direct application of IPM to skin yielded a 2.6-fold higher naproxen permeability than the application of IPM as gel. A greater amount of naproxen was absorbed from 1% test gel (pH 5) containing IPM than from 10% commercial gel (pH 7) containing no IPM. These results show that use of IPM can significantly improve the bioavailability of naproxen in topical preparations.

Animals↗
PubMed1995

Pharmacokinetic studies of methotrexate in plasma and synovial fluid following i.v. bolus and topical routes of administration in dogs.

PURPOSE: The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus i.v. and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. METHODS: A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. RESULTS: Peak MTX concentrations in SF occurred at 38 +/- 5 min following bolus i.v. dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 +/- 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 +/- 1.2 hr) and SF (12.7 +/- 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 +/- 0.21 hr) was longer than that in plasma (2.56 +/- 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at approximately 4 hr, lasting for approximately 20 hr. The bioavailability of MTX from the gel was 11.8 +/- 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. CONCLUSIONS: Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation.

Administration, Topical↗
PubMed1993

Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde.

The kinetics of conversion of methenamine to the active form formaldehyde were studied in pooled urine samples at 37 degrees in the pH range 4.9-6.5. Using a method for the determination of both formaldehyde and unhydrolyzed methenamine, the rate of formaldehyde formation in urine was found to be apparent first order and was pH dependent. Bactericidal concentrations of formaldehyde (> 28 micrograms ml-1) were achieved in 3 h in urine of pH 6.0 containing methenamine at 750 micrograms ml-1. There was no difference in the in vitro rate of conversion of methenamine to formaldehyde between the urine collected from normal subjects and the urine from subjects administered ascorbic acid. The rates of degradation of the mandelate and hippurate salts in buffer systems of various pH values did not differ significantly from those of methenamine base in urine adjusted to the same pH. The half-life of methenamine conversion to formaldehyde increased approximately 20 times from 20 h at pH 5.0 to about 400 h at pH 6.5. The data suggest that unless the urine is maintained below pH 6 only a small fraction of methenamine would be converted daily to formaldehyde and, thus, may explain the need for large doses of this drug in patients.

Anti-Infective Agents, Urinary↗
PubMed1992

Availability of phenindione-beta-cyclodextrin inclusion complex.

The inclusion complexation was occurred between beta-cyclodextrin (beta-CD) and phenindione (1) in aqueous solution. The complex formation was proved by solubility, dissolution and permeation study. The inclusion complex was prepared and its physicochemical properties was studied. 1 was combined with beta-CD in 1:1 molar ratio. Using the solubility data, the value of apparent stability constant obtained of 1/beta-CD complex was 492.7. The dissolution rate of 1 was increased in presence of beta-CD. The permeability coefficients of 1 were 7.86 x 10(-3), 4.76 x 10(-3) and 5.0 x 10(-3), corresponding to pure drug, its physical mixture with beta-CD and the inclusion complex, respectively. The presence of human albumin generally decreased the permeability coefficient of the drug. The reduction (79.5%) was found to be nearly equal in case of either pure 1 or its complex with beta-CD. Administration of 1 or its inclusion complex with beta-CD to rabbits increase prothrombin times, the effect was more pronounced in the complex form of drug than free one.

Animals↗
PubMed1991

Release rates of ketoprofen from poloxamer gels in a membraneless diffusion cell.

Release rates of ketoprofen from topical gels consisting of poloxamer 407 were evaluated using a membraneless diffusion cell with isopropyl myristate as the receptor medium. The effects of formulation variables such as polymer content (20-30%), drug (0.2-3.0%) and ethanol (0-20%) concentrations, pH (3.0-6.0), and temperature of the gels (25-45 degrees C) on drug release were studied. Release of ketoprofen from the gel decreased exponentially as the polymer concentration increased. Over the temperature range studied, the drug release rate appeared to correlate with the Arrhenius function. The change of the gel pH from 3 to 6 substantially increased the release rate of ketoprofen. The enhanced drug release in the presence of ethanol is attributed to the decrease in viscosity of the gel. With higher drug loading in the gel, an increase in the release rate, but a reduction of diffusion coefficient of the drug, was observed.

Diffusion↗
PubMed1990

Anti-inflammatory activity of ketoprofen gel on carrageenan-induced paw edema in rats.

The anti-inflammatory activity of a 1% ketoprofen gel containing 20% Pluronic F-127 was evaluated using the carrageenan-induced rat paw edema method. The activity of the gel was compared with that of other topical nonsteroidal anti-inflammatory drug (NSAID) preparations. The Pluronic gel formulation was significantly more effective against edema formation than other ketoprofen gels used. The 1% ketoprofen gel in the Pluronic base inhibited 53% of the carrageenan-induced edema formation as compared with 38% inhibition obtained with a 3% ketoprofen gel in a Carbopol-based formulation. The topical ED50 of the 1% ketoprofen gel was 2.2 mg/kg whereas the oral ED50 of ketoprofen in a suspension was 6.1 mg/kg, indicating that the relative equiponderal availability of the topical gel was nearly three times that of the oral suspension. The application of 50 mg of the 1% ketoprofen gel on the rat hind paw at various time intervals from 0 to 24 h prior to the carrageenan injection significantly inhibited edema formation in all groups of dosed rats. A significant correlation was found between the percent inhibition of rat paw edema and the log dose of ketoprofen injected subplantarly for the dose range between 0.1 and 10 micrograms/paw.

Administration, Topical↗
PubMed1986

Separation and quantitation of methenamine in urine by ion-pair extraction.

An ion-pair extraction technique is described for separating methenamine, a urinary tract antibacterial agent, from formaldehyde in human urine samples. Separation conditions are developed from extraction constants for the methenamine-bromocresol green ion-pair. The technique involves adsorption of the ion-pair onto a silica cartridge and elution with methylene chloride:1-pentanol (95:5). Methenamine is freed from the ion-pair by the addition of excess tetrabutylammonium iodide and converted to formaldehyde (determined spectrophotometrically) by reaction with ammonia and acetylacetone. Linear standard plots were obtained from urine containing methenamine which was diluted to 10-160 micrograms/mL. The lower limit of detection was 6 micrograms/mL of methenamine. Absolute recovery from urine was greater than or equal to 94.5%. The precision (CV) of detection of methenamine in the presence of formaldehyde was less than 2%, and less than or equal to 4.5% for the detection of formaldehyde in the presence of methenamine. No interferences were noted. The applicability of the method was demonstrated by analysis of human urine levels of both methenamine and formaldehyde following oral administration of a methenamine salt to a volunteer.

Adult↗
PubMed1984

Formation of encapsulated hydrophilic polymer beads by combined techniques of bead polymerization and phase separation.

A novel and rapid procedure for the preparation of hydrophilic polymer beads coated with ethyl cellulose has been developed. The coated polymer beads were prepared by combining techniques of bead polymerization and phase separation into a single step procedure. The final product has a size range of 200-1000 micrograms and consists of the core copolymer of 2-hydroxyethyl methacrylate-acrylamide and the barrier membrane of ethyl cellulose. Examination of beads in which amaranth dye was used as a model of active ingredient showed the dye to be uniformly distributed throughout the polymer matrix. Microscopic examination indicated that ethyl cellulose coated the core matrix. The effects of ethyl cellulose concentration, degree of agitation and molar ratio of monomers on the size of coated beads were investigated.

Cellulose↗
PubMed1984

Encapsulated hydrophilic polymer beads containing indomethacin as controlled release drug delivery systems.

Encapsulated hydrophilic polymer beads containing indomethacin were prepared by a combined technique of bead polymerization and phase separation. The drug delivery system consisted of the copolymer of 2-hydroxyethyl methacrylate and acrylamide as the core matrix and ethyl cellulose as the barrier membrane. The drug was incorporated into the polymer matrix during the formation of the beads. The system was found to be useful as a sustained release dosage form. Release of drug from the coated beads followed a zero-order rate up to 40% of the drug released. A linear relationship exists between the rate of release and the reciprocal amount of ethyl cellulose used for coating, indicating that the drug release was controlled by the coating thickness. Addition of polyvinyl pyrrolidone in the formulation significantly increased the amount of drug released. Blood level studies showed that drug absorption from the encapsulated beads was lower than that of indomethacin powder. It appeared that indomethacin was completely absorbed from the encapsulated beads.

Animals↗
PubMed1982

Improved and rapid high-performance liquid chromatographic assay for 13-cis-retinoic acid or all-trans-retinoic acid.

A rapid, specific, and sensitive reversed-phase high-performance liquid chromatographic (HPLC) assay for the quantitative determination of all-trans-retinoic acid (I) or 13-cis-retinoic acid (II) in rat serum without extraction of lyophilization is described. Chromatographic separation from retinol, serum components, and retinol acetate standard was achieved on octadecylsilane-coated particles with acetonitrile-1% ammonium acetate as th eluent. Serum samples (100 microliter) containing as little as 10 ng of retinoid were analyzed. Serum level profiles of rats dosed with the retinoids demonstrated the utility of the assay and indicated elimination half-lives of 0.58 and 0.92 hr for I and II, respectively.

Animals↗
PubMed1982

Blood level studies of all-trans- and 13-cis-retinoic acids in rats using different formulations.

Studies to determine the bioavailability of all-trans-retinoic acid from a microencapsulated product were carried out using rats as test animals. The microcapsules were tableted in rat food and individual rats given a tablet containing the equivalent of 10 mg of all-trans-retinoic acid. Comparisons were made with bioavailability data obtained after intravenous and oral administrations of a solution and a suspension. The elimination of all-trans-retinoic acid following intravenous administration of 1- to 5-mg doses occurred by dose-dependent kinetics. The half-lives for the terminal linear portion of the elimination phase after the plateau level were 0.78, 0.74, and 0.93 hr for the 1-, 2.5-, and 5-mg doses, respectively. Based on the doses administered and the relative area under the serum level curves, the all-trans-retinoic acid microcapsules were found to be approximately 34% as bioavailable as the solution dosage form and the microfine suspension 93% as bioavailable. The bioavailability of all-trans-retinoic acid in oral solution was approximately 40% of the intravenous dose. For comparison, rats were also dosed intravenously with 13-cis-retinoic acid, and this compound was found not to follow dose-dependent kinetics at similar dosage levels used for all-trans-retinoic acid.

Animals↗
PubMed1980

Distribution of tetracycline in red blood cells.

The distribution of tetracycline into human red blood cells was studied in vitro at 37 degrees. The drug was taken up rapidly by the cells, and its distribution equilibrium was reached after approximately 10 min of incubation. The steady-state distribution ratio of the drug between the red cells and extracellular fluid of 0.9% NaCl solution was 2.84, while the distribution ratio between the cells and the plasma solution was 0.9. The reduced cellular uptake in plasma was due to binding of the drug to plasma components. Calcium ions in plasma appeared to reduce tetracycline uptake by the red cells. The red cell distribution of tetracycline in dogs was in close agreement with the in vitro data using the washed human red cells. A dog suffering from severe hypoalbuminemia showed greater uptake of the drug by the erythrocytes, while a normal healthy dog exhibited the red cell-plasma distribution ratio of 0.98. The release rate of tetracycline from the preloaded cells into normal saline solution indicated that the release was directly proportional to the cellular concentration of the drug; the first-order release rate was approximately 1.38 hr-1.

Animals↗
PubMed1980

Kinetics of hydrolysis of methenamine.

The kinetics of degradation of methenamine were studied in citrate--phosphate buffers between pH 2.0 and 7.4 at 37.5 degrees. GLC was used to monitor the rate of hydrolysis. The conversion of methenamine to formaldehyde was found to be pH dependent in the buffers of constant ionic strength, with the reaction half-life decreasing from 13.8 hr at pH 5.8 to 1.6 hr at pH 2.0. The kinetics of degradation also were measured at 47, 57, and 67 degrees, and the reaction obeyed the Arrhenius relationship. At pH 2.0, the activation energy was calculated to be 23.5 kcal/mole; at pH 5.1, it was 12.0 kcal/mole.

Formaldehyde↗
PubMed1979

Examination of blood clobazam levels and several pupillary measures in humans.

The State-Trait Anxiety Inventory was administered to 15 subjects before initiation of the experiment. Three subgroups of five subjects were defined by computing the unweighted sum of the state and trait anxiety scores. A 40-mg dose of clobazam, a 1.5-benzodiazepine, was administered to each subject and repeated with two additional dosage forms following a 2-week washout period. Blood samples were withdrawn, and blood levels were determined by fluorometric analysis. Additionally, pupillary measures of critical flicker fusion, constriction, and dilation in response to a cognitive task were obtained at 0, 2, 4, and 6 hr. A repeated measures analysis of variance revealed that blood levels were, as expected, statistically different over time and dosage form. The pupillary constriction mirrored the blood levels in statistical patterns. The pupillary measure of cognition related to the anxiety state after the performance effects of the cognitive task were statistically removed. The results suggest that clobazam has less immediate human effect than does diazepam.

Anxiety↗
PubMed1978

Plasma levels of clobazam after three oral dosage forms in health subjects.

As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement.

Administration, Oral↗
PubMed1978

Interaction of tricyclic antipsychotic and antidepressant drugs with 1-anilino-8-naphthalenesulfonic acid.

The binding of 1-anilino-8-naphthalenesulfonic acid to selected tricyclic antipsychotic and antidepressant drugs was studied by fluorescence spectroscopy. The acid exhibited an increase in fluorescence intensity accompanied by a hypsochromic shift of the emission lambdamax in the presence of these drugs. These fluorescence characteristics, in addition to those of acid-drug complexes after addition of potassium chloride or urea, suggested that binding was hydrophobic. The spectra also provided evidence regarding the importance of certain structural features of drugs in determining the nature of binding.

Anilino Naphthalenesulfonates↗