PubMed Health⌕ Search

Biomedical subjects

A H Ghanem

Publications and source records attributed to A H Ghanem.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of temperature upon the permeation of polar and ionic solutes through human epidermal membrane.

The temperature dependence of in vitro permeation through human epidermal membrane (HEM) was determined for urea, mannitol, tetraethylammonium ion (TEA), and corticosterone. The effect of temperature upon HEM electrical resistance was also measured. The majority of the experiments involved measuring the permeability coefficients of a specific permeant at 27 degrees C and 39 degrees C for a given HEM sample, the electrical resistance was also measured at each temperature. Similar experiments were also conducted with a model synthetic porous membrane. The effect of temperature was quantitated as the ratio of the permeability at 39 degrees C to the permeability at 27 degrees C for each permeant. These ratios observed for HEM with urea, mannitol, and TEA as the permeants were 1.66 +/- 0.05, 1.76 +/- 0.14, and 1.71 +/- 0.11, respectively. The change in temperature was shown to have a similar effect upon the electrical conductance of the HEM samples. The observed ratio for corticosterone permeation was 4.5 +/- 0.4. The experimental ratios observed for the three polar/ionic permeants were shown to approach those obtained from the model porous membrane and differed greatly from the ratio observed for the more lipophilic corticosterone, indicating differences in the effective transport mechanism/pathway for these classes of permeants. The permeability of urea was also observed to be inversely proportional to the electrical resistance of the HEM samples; this relationship was shown to be independent of temperature over the temperature range studied. The temperature dependence data and the observed relationship between urea permeability and electrical resistance strongly support the existence of a porous permeation pathway through the HEM as an operative diffusional route for polar-ionic permeants.

Corticosterone↗
PubMed1994

Quantitative in vivo iontophoretic studies.

An experimental methodology was developed to evaluate the physicochemical basis for in vitro-in vivo correlations in iontophoretic delivery situations. This experimental methodology can be used to quantitatively evaluate the extent of interaction between chemical permeation enhancers and iontophoresis for drug delivery. The inherent advantages of using Ag/AgCl electrodes are fully exploited to control pH and minimize depletion of permeant during prolonged periods of iontophoresis.

Animals↗
PubMed1994

Studies on the effects of applied voltage and duration on human epidermal membrane alteration/recovery and the resultant effects upon iontophoresis.

The effects of applied voltage and the duration of application upon human epidermal membrane (HEM) alterations and recovery were investigated. All experiments were conducted using a two-chamber diffusion cell with constant DC voltage (250-4000 mV) applied over a predetermined period, and HEM changes were monitored by measuring the electrical resistance before and after voltage termination. The key findings were that the rate of decrease in resistance was strongly dependent upon the applied voltage, the reversible recovery times were dependent upon both the magnitude and the duration of the applied field (frequently were several orders of magnitude greater than times for attaining significant resistance reduction), and reversible recovery times were much longer when lower voltages were applied for longer times to attain the same decrease in electrical resistance than for higher voltages at short times. These findings closely parallel those obtained on electrical breakdown/recovery of bilayer membranes (electroporation). The second part of this work examined the hypothesis that decreases in HEM electrical resistance induced by the applied voltage are accompanied by proportional increases in HEM permeability. A study was designed to test this hypothesis involving a four-stage protocol with HEM: passive transport, 250-mV iontophoresis, 2000-mV iontophoresis for 10 min, then back to 250-mV iontophoresis. The data obtained strongly support the view that the HEM alterations induced by the electric field result in pore formation and in the expected changes in HEM permeability.

Diffusion↗
PubMed1994

Transport of beta-estradiol in freshly excised human skin in vitro: diffusion and metabolism in each skin layer.

This paper describes an experimental and theoretical evaluation of beta-estradiol (E2) transport in post-surgery fresh human skin in vitro. Necessary auxiliary experimental methods were newly developed for these studies. The experimental fluxes of E2 and the metabolite, estrone (E1), using the dermis, stripped skin, and split-thickness skin were consistent with a model considering the human skin as a three-layer (stratum corneum, viable epidermis, and dermis) membrane with the enzyme activity mainly residing in the basal layer of the viable epidermis. The diffusion and metabolism parameters for each skin layer were determined in the overall transdermal transport of E2. Compared to fresh hairless mouse skin, fresh human skin appears more resistant to the stratum corneum diffusion of E2 and is much less capable of metabolizing E2 to E1. These in vitro results have been extrapolated to the possible in vivo human skin situation with blood vessels directly beneath the viable epidermis providing "sink" conditions a short distance from the dermo-epidermal junction. The model analysis has demonstrated that there would be less metabolism and that a much smaller amount of the transdermal metabolite (E1) would be taken up by the blood capillary due to the shorter dermis path length for permeants in vivo than in the in vitro case using dermatomed split-thickness skin.

Biological Transport↗
PubMed1994

Hindered diffusion of polar molecules through and effective pore radii estimates of intact and ethanol treated human epidermal membrane.

The in vitro passive transport of urea, mannitol, sucrose and raffinose across intact and ethanol treated human epidermal membrane was investigated. The intent of this study was to characterize the barrier properties and permeation pathways of these membranes for polar permeants under passive conditions. Based upon the relative permeabilities of these four solutes and hindered diffusion theory, the experimental data was adequately modeled for both membrane systems according to permeation through a porous membrane. Effective pore radii estimates for intact human epidermal membrane fell between 15 A to 25 A while similar estimates fell compactly between 15 A to 20 A for ethanol treated human epidermal membrane. Similarities between the relative permeabilities of human epidermal membrane for the four permeants studied and the relative permeabilities of these same permeants through ethanol pretreated human epidermal membrane indicate that significant similarities exist between the permeation pathways for both membrane systems. The results of this study have important implications for transdermal drug delivery in general and more specifically for strategies of designing effective chemical permeation enhancement systems.

Diffusion↗
PubMed1992

Factors to be considered in the evaluation of bioavailability and bioequivalence of topical formulations.

In this paper, an attempt is made to find functional definitions of bioavailability and bioequivalence for topical products and to examine critical factors that influence topical bioavailability and bioequivalence. A physical model approach for quantifying the problem and increasing our understanding is presented here. The key assumptions are (1) that the target site is in the lower epidermis (basal layer) or in the dermis, and (2) that it is the thermodynamic activity (i.e., the free drug concentration, C*, of the active drug species) at the target site that is the true correlate of drug effectiveness. Studies initiated to implement the physical model approach involved first validating a 'three-tiered' model for finite dose drug uptake/transport in skin with experimentally determined input parameters (partition coefficient, K, and steady-state permeability coefficients, P, for the stratum corneum, viable epidermis, and dermis). Hydrocortisone was used as the model drug with hairless guinea pig skin as the model membrane. The physical model is used to show, via the C* concept, how formulation factors may influence bioavailability and bioequivalence. Finally, a method is presented for predicting the efficacy of topical formulations employing appropriate in vitro data and physical model calculations.

Administration, Topical↗
PubMed1992

Model studies of epidermal permeability.

An in vitro physical model approach for describing and predicting transport of molecules and ions across skin is examined. The proposed model is represented by two transport-resistant layers in series: the stratum corneum and the epidermis plus dermis. The stratum corneum is regarded as the principal barrier to transport and is composed of two parallel pathways: the lipoidal pathway and the pore pathway. The epidermis-dermis is treated as a porous membrane. The model predicts three regimes for the transport behavior of permeants, and these predictions have been compared with experimental permeability coefficient data obtained with hairless mouse skin in a two-chamber (aqueous) diffusion cell. The model predicts (1) that extremely lipophilic molecules are rate-limited by the epidermis-dermis and have a limiting permeability coefficient value; (2) that extremely polar permeants are rate-limited by the pore pathway of the stratum corneum with its limiting permeability coefficient; and (3) that permeants with intermediate polarity are transported via the lipoidal pathway and exhibit a lipophilicity-dependent permeability coefficient. Experimental data involving a large number of permeants are found to be consistent with these model predictions. The model approach also has been applied in the study of the mechanism(s) of skin transport enhancement induced by short-chain alkanols in aqueous media. A possible mode of enhancing the lipoidal pathway at low concentrations of the alkanols may involve the polar head region of the lipid bilayer or the region slightly below the polar head plane, or both; alkanols may solvate the lipid-water interface, intercalating and disrupting the interactions of the upper regions of the alkyl chains and the interactions between the polar head groups. This could result in an increase in both diffusivity and partitioning tendency for a permeant in this microenvironment. At higher alkanol concentrations, the pore pathway becomes dominant in controlling the transport of the permeants across the stratum corneum.

Alcohols↗
PubMed1989

Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery.

Three factors are of primary importance in determining the iontophoretic flux of a charged solute: the electrochemical potential gradient across the skin, an increase in skin permeability to passive transport due to iontophoresis (loosely defined as skin damage), and a current-induced water flux. The latter two factors can also affect the transport of uncharged solutes during iontophoresis. A method of correcting for the skin damage effect is introduced. The contributions of the water transport effect relative to that of the applied voltage drop for charged solutes is estimated. It is shown that the water transport contribution is generally lower than the contribution due to the applied voltage drop. The observed iontophonetic flux of the enhancement factors due to the applied voltage drop alone are compared with the theoretical predictions based on the constant field assumption. It is shown that the theoretical predictions are higher than the experimental observations. This work also examines, for the first time, a synergism of iontophoresis and pretreatment with a chemical penetration enhancer as a means for delivering high molecular weight polypeptides. It is shown that a 2-h pretreatment with absolute ethanol followed by iontophoresis dramatically increases the permeability coefficient of insulin through human skin.

Administration, Cutaneous↗
PubMed1981

Physical properties and dissolution profiles of acetaminophen and acetylsalicyclic acid tablets made from sucrose-based vehicles.

Di-pae, Sugartab and Nu-Tab were used as direct compressible vehicles for acetaminophen and acetylsalicylic acid tablets. Direct compressible grades on lactose and Avicel were used as vehicles for comparison. Three different packing fractions were employed for tabletting acetaminophen and acetylsalicylic acid. The physical properties and dissolution characteristics of the prepared tablets depend on their packing fraction i.e. the mechanical strength, and disintegration and dissolution time are lowest at the lowest packing fraction and vice versa. It was found that the time required for maximum dissolution rate (t90) of drug was usually longer than the disintegration times of tablets and also t90 of acetylsalicylic acid was found to be faster than that of acetaminophen with all tested vehicles.

Acetaminophen↗
PubMed1981

The influence of binder type and concentration on the physical characteristics of calcium carbonate granules and their corresponding tablets.

Most studies involving binders are concerned with the properties of the final product. Very little has been done at comparing the mechanical properties of the granules, the force required to crush the tablets and the compression behavior. The aim of this investigation was to study the effect of different concentrations of five binders namely gelatin, PVP, methylcellulose, syrup and Eudragit E on the mechanical and physical properties of calcium carbonate granules and correlating that with the characteristics of the corresponding tablets. A template method was used for the preparation of calcium carbonate granules. The wet granules were dried for 34 h in air oven at 60 degrees C and were conditioned for a minimum of 2 h at 50% relative humidity before testing or tableting as this corresponds approximately to ambient conditions. The granules, were separated into different size fractions using the sieve analysis method, and were then measured for crushing strength (K), friability (%), flow ability, bulk volume and tap density. The granules possessing the best mechanical and physical characteristics were used for tableting. The compact obtained were also evaluated for both mechanical and physical properties. It was found that increasing the binder concentration was followed by an increase in the mean particle diameter, harder granules (-kt = ln Wa divided by W + Wb . db divided by W . da) and reduction in tap density. Except for those prepared with 2% methylcellulose and 30% syrup, all tablets prepared from granules with optimum properties are found to satisfy U.S.P. requirements of weight, thickness, disintegration time and mechanical properties.

Calcium Carbonate↗
PubMed1980

On the diffusion of chloramphenicol from oleaginous ointment bases.

The rate of diffusion of chloramphenicol from oleaginous ointment bases was investigated. It was found that the rate of diffusion of the drug from beeswax is markedly higher than that from hard paraffin. Cetrimide, whether present in the waxy base or in the aqueous diffusion medium, enhances markedly the rate of diffusion of chloramphenicol. The effect of cetrimide is, however, more pronounced in the case of hard paraffin. Incorporation of triolein in the waxy bases markedly increases the diffusion of the drug. This was correlated to changes in certain rheological parameters of the bases in presence of triolein.

Chloramphenicol↗
PubMed1979

Stability of indomethacin solubilized system.

Physical and chemical stability testing was carried out for indomethacin in the form of solution, syrup and elixir solubilized by Tween 80 and Brij 99. It was found that sucrose and alcohol markedly stabilize the indomethacin solution.

Chemical Phenomena↗
PubMed1978

Effect of liquid additives on release of chloramphenicol from ointment bases.

1, 3 and 5% water, ethyl alcohol, glycerol and propylene glycol were incorporated into oleaginous, absorption, emulsion (O/W and W/O) and water-soluble ointment bases (resp.) containing 5% of chloramphenicol and diffusion rate via the dialysis method was measured for 2 h. The rate of release was found to be greater from water-soluble bases than from the other bases, since rates from oleaginous, absorption and W/O emulsion bases were found to be the least in this respect. The effect of liquids added to these bases on drug release was found to be less pronounced than that obtained with water-soluble and O/W emulsion bases. For O/W emulsion bases the addition of ethyl alcohol increased the release of chloramphenicol as its concentration was increased. Propylene glycol increased the release at a concentration of 3%, but higher concentration produced opposite results. Glycerol was found to have a little effect in 5% concentration, but it increased the release as the concentration dropped to 3% concentration.

Chloramphenicol↗
PubMed1978

Solubilization of indometacin.

Three methods were employed for the solubilization of indometacin as an example of antirheumatic drugs, employing:--Non-ionic surface-active agents such as Tween 80 and 40, Myrj 53 and Brij 99,--urea and sodium citrate--urea-indometacin coprecipitate. The solubility of indometacin by nonionic surface active agents was in the following order: Tween 80 and Brij 99 greater than Tween 40 greater than Myrj 53. The efficiency of solubilization by these surfactants decreased as the polyoxyethylene chain increased. Urea increases the solubility of indometacin due to enhancing the solvation of the drug by water. Up to a concentration of 0.2 M sodium citrate increases the solubility of indometacin, followed by a sharp decline in the solubility by increasing its concentration of sodium citrate. Urea-indometacin coprecipitate show slight increase in the solubility of the drug.

Citrates↗