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Biomedical subjects

B W Barry

Publications and source records attributed to B W Barry.

At least 55 records · Page 3Linked to original sources
PubMed1985

Vapour and liquid diffusion of model penetrants through human skin; correlation with thermodynamic activity.

This work investigates vapour and liquid permeation through human skin of model penetrants benzyl alcohol, benzaldehyde, aniline, anisole and 2-phenylethanol applied in model vehicles butanol, butyl acetate, isophorone, isopropyl myristate, propylene carbonate, toluene, n-heptane and water. Vapour permeation was a linear function of thermodynamic activity as measured by headspace gas chromatography, except when the vehicle was n-heptane. Liquid permeation did not always follow simple thermodynamic predictions, e.g. for the penetrant, benzyl alcohol, when the vehicle damaged the skin (toluene, n-heptane) or when propylene carbonate produced low fluxes and isopropyl myristate, high values. At comparable thermodynamic activities, liquid fluxes were often ten-fold higher than vapour fluxes, and these differences were reflected by the partition coefficients and the amount of penetrant entering the stratum corneum membrane. The conclusion was that liquid fluxes were membrane controlled, whereas an interfacial effect probably contributed to low vapour permeation.

Benzyl Alcohol↗
PubMed1985

Optimization of bioavailability of topical steroids: non-occluded penetration enhancers under thermodynamic control.

The non-occluded vasoconstrictor test under thermodynamic control assessed the effect of penetration enhancers on the topical bioavailability of a model steroid betamethasone 17-benzoate, using aqueous dimethylisosorbide (DMI) as a standard solvent. The aqueous potential penetration enhancers used were at 10% steroid saturation i.e. ideally at identical steroid thermodynamic activity. In the vasoconstrictor test, 2-pyrrolidone, N-methyl-2-pyrrolidone, propylene glycol with oleic acid, propylene glycol with azone and dimethylformamide (DMF) increased the steroid bioavailability compared with that from DMI, while propylene glycol alone produced borderline improvement. Azone and oleic acid in combination with DMI or Betnovate cream did not increase the steroid bioavailability indicating the importance of the correct cosolvent. The pyrrolidones established superior stratum corneum reservoirs compared with DMI, the other vehicles being similar to DMI. It was concluded that excepting DMI, the solvents tested were penetration enhancers for the model steroid betamethasone 17-benzoate and are worthy of further study. However, irritant effects may make some of them unacceptable for clinical use.

Administration, Topical↗
PubMed1984

Optimization of bioavailability of topical steroids: penetration enhancers under occlusion.

The occluded vasoconstrictor assay was used to assess the effect of penetration enhancers on the topical bioavailability of a representative steroid, betamethasone 17-benzoate, with dimethylisosorbide (DMI) as a reference solvent. In the initial test, only N-methyl-2-pyrrolidone (NMP) increased the steroid bioavailability; acetone, dimethylformamide (DMF), 2-pyrrolidone (2-P), and 1-ethyl-2-pyrrolidone (EP) were equal to DMI, while propylene glycol (PG) and N,N-diethyl-m-toluamide (DEET) were poorer. Reocclusion showed that NMP and acetone established superior stratum corneum reservoirs; DMF, 2-P, EP, and PG were as effective as DMI but DEET was less effective. It was concluded that occlusive hydration and lack of thermodynamic control may have obscured the enhancing abilities of the solvents, 2-P, NMP, EP, DMF, and DEET induced erythema in some volunteers, although this was usually short-lived.

Acetone↗
PubMed1984

Effects of freezing on human skin permeability.

The percutaneous absorption of water was measured in-vitro at 30 degrees C for pale caucasian abdominal skin which had been stored at -20 degrees C for up to 466 days and compared with fresh skin. Prolonged freezing of the skin did not affect the absorption of water which had a mean permeability coefficient of 1.71 +/- 0.62 X 10(-3) cm h-1 (180 diffusion experiments with 39 skin specimens). No significant difference was found between the absorption of water through human skin which was fresh or had been frozen. The mean permeability coefficient for skin which had not been frozen was 1.30 +/- 0.55 X 10(-3) cm h-1 for 6 skin specimens.

Aged↗
PubMed1983

Penetration enhancers for human skin: mode of action of 2-pyrrolidone and dimethylformamide on partition and diffusion of model compounds water, n-alcohols, and caffeine.

Penetration-enhancing solvents may modify diffusional routes through the stratum corneum and the partitioning of drugs into these pathways. To investigate the mechanisms of action of enhancers, steady-state fluxes were measured in vitro for polar methanol, nonpolar octanol, and an intermediate compound, caffeine, selected as model penetrants; human stratum corneum conditioned on both sides with water or accelerants (2-pyrrolidone or dimethylformamide solutions) was used. We determined partition, permeability, and apparent diffusion coefficients, and derived the standard free energy of transfer of the methylene group from water to stratum corneum (-423 cal mol-1); less negative values were obtained for transfer from 2-pyrrolidone solutions. We conclude that for these model compounds, and taking a fully hydrated membrane as a standard: (a) 2-pyrrolidone enhances permeation through the polar route of the skin by increasing the diffusivity, and reduces passage through the nonpolar route by decreasing diffusivity and partitioning, (b) dimethylformamide promotes polar route absorption by raising diffusivity and partitioning and reduces nonpolar absorption by decreasing both parameters, and (c) for caffeine, the markedly increased absorption (15-fold) caused by dimethylformamide is associated with damage to the membrane.

Aged↗
PubMed1983

Possible dosage regimens for topical steroids, assessed by vasoconstrictor assays using multiple applications.

The bioavailabilities and activities of three amcinonide preparations and Betnovate cream were assessed using three multiple-dosage regimen vasoconstrictor assays in 10 volunteers. Applications were made once daily, twice daily and every alternate day with an initial three times daily loading dose applied on the first day only. Blanching responses first increased and then decreased due to tachyphylaxis. It is proposed that clinically the most advantageous dosage regimen is a once daily application with no loading dose.

Administration, Topical↗
PubMed1982

Optimization of bioavailability of topical steroids: thermodynamic control.

In theory, under strictly defined ideal conditions, the bioavailability of a drug from a topical formulation should depend only on the thermodynamic activity of the medicament in the base. We tested this fundamental postulate using a steroid as the test drug, formulated in a series of solutions and gels at 90% saturation, i.e., ideally at constant thermodynamic activity. The in vivo assessment method was the occluded vasoconstrictor test in humans. For most systems, this simple measure of thermodynamic activity correlated with drug bioavailability as assessed by the blanching response. Where there were differences, we have rationalized them in terms of penetration enhancement, irritancy, dehydration of the stratum corneum, or steroid binding in the base, although such factors have not been explicitly demonstrated.

Administration, Topical↗
PubMed1977

Bioavailability and activity of topical corticosteroids from a novel drug delivery system, the aerosol quick-break foam.

Experiments were conducted to: (a) compare the bioavailability of betamethasone benzoate in a quick-break aerosol foam and semisolid dosage forms, (b) compare the activity of betamethasone benzoate, betamethasone valerate, clobetasol propionate, triamcinolone acetonide, desonide, flumethasoid reservoir formation in skin, and (d) assess the effect of a natural moisturizer. Efficacy was determined by a graded response 6-hr occluded vasoconstriction test with subsequent reocclusion for reservoir demonstration. Moisturizer effect was assessed by a nonoccluded vasoconstriction test using "plain" and sodium 2-pyrrolidone-5-carboxylate-containing concentrates on arms pretreated with water or moisturizer. The activities of betamethasone benzoate concentrate, collapsed foam, ointment, and gel were similar and significantly better than the activity of the cream. Clobetasol propionate was significantly better than the other medicated concentrates, which were equivalent. Steroid-induced blanching decreased in the presence of a moisturizer.

Administration, Topical↗
PubMed1977

Vasoconstrictor activities and bio-availabilities of seven proprietary corticosteroid creams assessed using a non-occluded multiple dosage regimen; clinical implications.

The bio-availabilities and activities of commercial creams (Metosyn, Synalar, Betnovate, Locoid, Alphaderm, Dioderm and Efcortelan 1%) were assessed using a multiple dosage regimen vasoconstrictor assay in ten volunteers. The blanching response first increased but then diminished with continued application over a 5-day period: following a 2-day 'resting period', when no steroid was applied, the application sites recovered considerably but tachyphylaxis again resulted from subsequent repeated applications. Acute tolerance occurred with the hydrocortisone formulations (Alphaderm, Dioderm and Efcortelan 1%) in a manner similar to that observed with the potent preparations. Metosyn was significantly more active (P less than 0.05), and Efcortelan 1% was significantly less active (P less than 0.05), than the other formulations. Apart from the reversal of Dioderm and Alphaderm the rank order of preparations was similar to that previously noted in the 6 h occluded single-application vasoconstrictor test. The results may have significance in dosage from design and application for topical corticosteroid formulations.

Administration, Topical↗
PubMed1977

Permeation of oestrone, oestradiol, oestriol and dexamethasone across cellulose acetate membrane.

The permeation across cellulose acetate of three oestrogens, differing only in the number of hydroxyl groups attached to the nucleus, and a 'standard' steroid, dexamethasone, was investigated using the lag-time method for calculating diffusion parameters, between 10 and 40 degrees. Diffusion coefficients for the similarly-sized oestrogens were relatively insensitive to marked changes in polarity, but increased permeation was correlated with increased partition coefficients, decreased polarity and fewer hydroxyl groups on the nucleus. Permeation increased with temperature and energies of activation were calculated from Arrhenius-type plots. Ep values ranged from 4-84 k cal mol-1 (20 kJ mol-1) for the least polar steroid (oestrone) to 6-91 k cal mol-1 (29 kJ mol-1) for the most polar steroid (oestriol). The results implied that steroid diffusion occurred through aqueous membrane channels, but that it was impeded to various extents by both obstruction and polar interaction effects.

Cellulose↗
PubMed1976

Proprietary hydrocortisone creams. Vasoconstrictor activities and bio-availabilities of six preparations.

Six proprietary hydrocortisone creams were evaluated for vasoconstrictor activities and bio-availabilities using an occluded blanching test. Statistical analysis showed a significant difference between the formulations. Dioderm, containing 0-1% hydrocortisone, was significantly more active than the 1% hydrocortisone creams--Alphaderm, Calmurid HC, Efcortelan and Vioform-Hydrocortisone. There was no significant difference between Dioderm and Dioderm C. Unlike creams containing more potent corticosteroids the hydrocortisone formulations apparently failed to produce steroid reservoirs in the stratum corneum as assessed by the blanching response.

Administration, Topical↗
PubMed1976

Solubilization of hydrocortisone, dexamethasone, testosterone and progesterone by long-chain polyoxyethylene surfactants.

Solubility and dialysis methods were used to study the solubilization of hydrocortisone, dexamethasone, testosterone and progesterone in aqueous long-chain polyoxyethylene non-ionic surfactant solutions. Partition coefficients, Km, between micellar and aqueous phases were calculated between 10-50 degrees. Km decreased with temperature and polyoxyethylene chain length but increased with decrease in steroid polarity. The standard free energy change, deltaGOS, for the solubilization of the steroids decreased with decrease in steroid polarity and surfactant hydrophilic chain length but was essentially independent of temperature. The enthalpies and entropies for the process were determined from the variation of Km with temperature. deltaHOS and deltaSOS increased with decreasing steroid polarity but were essentially independent of temperature and polyoxyethylene chain length.

Chromatography, Thin Layer↗
PubMed1976

Influence of non-ionic surfactants on permeation of hydrocortisone, dexamethasone, testosterone and progesterone across cellulose acetate membrane.

The lag-time method of diffusion has been used to investigate permeation of hydrocortisone, dexamethasone, testosterone and progesterone across cellulose acetate membranes between 10 degrees and 40 degrees. The process depended mainly on membrane-water partition coefficients of the steroids so that the least polar compound permeated the fastest. Permeation generally increased with increasing temperature and from the temperature dependance of the diffusion coefficient, energies of activation were derived. The varied from 2.4 kcal mol(-1) for the least polar steroid, progesterone, to 7.4 kcal mol(-1) for the most polar, hydrocortisone. n-C16 Polyoxyethylene surfactants when present below and above the cmc increased the steroids permeation rates. Varying the polyoxyethylene chain length (OE equals 17-63) did not significantly affect permeation rates, suggesting that the enhancing effect of surfactants arises from their hydrophobic group.

Acetates↗
PubMed1976

Bioavailability of topical steroids.

This paper review our modification of the vasoconstrictor (blanching) assay for topical corticosteroids using human volunteers, which we have improved and extended so that it may be used as a useful screening test for clinical efficacy besides being employed to determine the bioavailability of steroids from topical bases. Work is reported on the blanching activities of (1) 14 novel steroids in ethanol, (2)hydrocortisone 17-butyrate in eight topical vehicles, (3) betamethasone 17-benzoate in foam, ointment, cream and gel bases, and (4) 61 commercial formulations used in Great Britain. Pharmacokinetic/pharmacodynamic relationships are discussed as aids to optimizing topical steroid treatment.

Administration, Topical↗
PubMed1975

Vasoconstrictor activities of some novel synthetic steroids in alcoholic solution.

Ethanolic solutions of 8 new, topically active, anti-inflammatory steroids and 1 standard (betamethasone 17-valerate) were assessed with a modified vascoconstrictor assay. Pallor was graded at 17 reading times for determination of complete blanching curves. The compounds were ranked by three methods: (1) summed % total possible score, (2) area under the blanching profile, and (3) square root transformation of sum of scores divided by number of volunteers, for statistical differentiation of the solutions. Conclusions on structure-vasoconstrictor activity relationships were that substitution or removal of 21 hydroxy provided compounds with a wide range of activity. Poor activity correlated with a hemisuccinate salt grouping at position 21, or the absence of 11beta-hydroxy.

Administration, Topical↗
PubMed1975

Comparative bio-availability and activity of proprietary topical corticosteroid preparations: vasoconstrictor assays on thirty-one ointments.

Thirty-one proprietary corticosteroid ointments were evaluated for vasoconstriction using an occluded blanching test. The results were expressed as three parameters: (1) area under the blanching curve, (2) summed % total possible score, and (3) square root transformation of sum of scores divided by number of volunteers. Experiments were performed to (a) compare the bio-availability and activity of the ointments, (b) determine the effect of antimicrobial additivies, and (c) assess the retention of steroids in the skin. Scores for the additivie-containing and 'plain' preparations were within 90% except for Locorten-Vioform/Locorten (58%). A steroid reservoir in the skin was demonstrated lasting for 8-14 days. Selected preparations were re-tested by a non-occluded method. The results for the ointments were compared with those previously obtained using the corresponding creams.

Administration, Topical↗
PubMed1975

The effect of mucin on the bioavailability of tetracycline from the gastrointestinal tract; in vivo, in vitro correlations.

The bioavailability of tetracycline in the presence and absence of a porcine gastric mucin dispersion (1% W/V) has been studied by in vivo perfusion of the rat small intestine, the rat everted gut, a diffusion cell technique and the Sartorius Absorption Simulator Apparatus. In the presence of the mucin preparation an approximate 50% reduction in the numerical values of each of the parameters used to measure the tetracycline movement across the membrane was found. The physiological significance of each technique and the methods themselves are discussed. Interaction of tetracycline with the porcine gastric mucin preparation is considered in relation to the molecular structure of mucus. The results suggest the drug is bound in some way, as yet undefined, to the mucin macromolecule.

Animals↗