A comparison between in vitro rat and human and in vivo rat skin absorption studies

2004 ◽  
Vol 23 (9) ◽  
pp. 421-430 ◽  
Author(s):  
B Van Ravenzwaay ◽  
E Leibold
Keyword(s):  
Human Skin ◽  
Systemic Exposure ◽  
In Vitro Study ◽  
Skin Penetration ◽  
Dermal Absorption ◽  
Rat Skin ◽  
Dermal Penetration ◽  
Rat Study

In vitro skin penetration rates in rat and man were compared to those obtained in vivo in rats. Saturation of absorption was frequently observed at higher exposure levels in in vitro and in vivo. Lipophilic compounds showed the highest penetration rates through rat skin in vitro. In all cases in vitro dermal penetration through rat skin was higher than in vivo. Thus, the in vitro study may serve as a first tier test. The in vivo data suggest an inverse relationship between molecular weight and the rate of dermal absorption for lipophilic as well as hydrophilic compounds. Rat skin was more permeable to all tested substances than human skin (mean difference 10.9-fold). Thus, the systemic exposure of humans may be significantly overestimated if risk assessment is based only on the results of an in vivo rat study, because human skin is less permeable than rat skin. It would appear, therefore, that an estimate of actual dermal penetration through human skin should be based on the combined use of in vivo and in vitro data, using the following equation: %Human dermal penetration =(%rat in vivo dermal penetration) (See PDF for Formula)

In-vivo and in-vitro study of control of rat skin optical properties by action of 40%-glucose solution

2001 ◽  
Author(s):  
Alexey N. Bashkatov ◽  
Elina A. Genina ◽  
Irina V. Korovina ◽  
Yurii P. Sinichkin ◽  
Olga V. Novikova ◽  
...  
Keyword(s):  
Optical Properties ◽  
Glucose Solution ◽  
In Vitro Study ◽  
Vitro Study ◽  
Rat Skin

scholarly journals Nanostructured Lipid Carrier Gel for the Dermal Application of Lidocaine: Comparison of Skin Penetration Testing Methods

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 310 ◽  
Author(s):  
Stella Zsikó ◽  
Kendra Cutcher ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Attila Gácsi ◽  
...  
Keyword(s):  
Drug Release ◽  
Human Skin ◽  
Ex Vivo ◽  
Study Drug ◽  
Skin Penetration ◽  
Human Epidermis ◽  
Nanostructured Lipid Carrier ◽  
Experimental Findings

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

In-vivo and in-vitro study of control of rat skin optical properties by action of osmotical liquid

2000 ◽  
Author(s):  
Alexey N. Bashkatov ◽  
Elina A. Genina ◽  
Irina V. Korovina ◽  
Vyacheslav I. Kochubey ◽  
Yurii P. Sinichkin ◽  
...  
Keyword(s):  
Optical Properties ◽  
In Vitro Study ◽  
Vitro Study ◽  
Rat Skin

3D-printed chitosan-based scaffolds: An in vitro study of human skin cell growth and an in-vivo wound healing evaluation in experimental diabetes in rats

2018 ◽  
Vol 199 ◽  
pp. 593-602 ◽  
Author(s):  
Claudio Intini ◽  
Lisa Elviri ◽  
Jaydee Cabral ◽  
Sonya Mros ◽  
Carlo Bergonzi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Growth ◽  
Human Skin ◽  
Experimental Diabetes ◽  
In Vitro Study ◽  
Vitro Study ◽  
Skin Cell ◽  
3D Printed

Use of Percutaneous Absorption Data in Risk Assessment

1989 ◽  
Vol 8 (5) ◽  
pp. 815-827 ◽  
Author(s):  
C. A. Franklin ◽  
D. A. Somers ◽  
I. Chu
Keyword(s):  
Risk Assessment ◽  
Percutaneous Absorption ◽  
Dermal Absorption ◽  
In Vivo Studies ◽  
Absorption Data ◽  
Regulatory Decision ◽  
Dermal Penetration ◽  
High Doses

Assessment of risks to humans associated with the use of chemicals requires knowledge of the hazard (toxicity) of the chemical and level of human exposure. Hazard assessment is often based on animal bioassays and quantitative exposure estimates of dermal exposure obtained from studies monitoring workers. Because human skin is an effective barrier to many chemicals, it cannot be assumed that the deposited dose is equivalent to the systemic dose. However, an estimate of systemic dose may be derived by multiplying the deposited dose by the percentage of percutaneous uptake. This correction can have major impact on the regulatory decision, because the adjusted dose used in the risk calculation may be reduced significantly, especially at high doses, when the uptake is not linearly proportional to the exposure. It is therefore important that the dermal absorption value be accurate. As outlined in this paper, numerous factors can affect percutaneous absorption. Nevertheless, many regulatory agencies will consider the use of percutaneous absorption data derived from in vivo studies to adjust the dermally deposited dose to that delivered systemically. Numerous issues must be resolved before in vitro dermal penetration studies can be used for risk assessment.

scholarly journals Human Skin Penetration of Flufenamic Acid: In Vivo/In Vitro Correlation (Deeper Skin Layers) for Skin Samples from the Same Subject

2002 ◽  
Vol 118 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Heike Wagner ◽  
Claus-Michael Lehr ◽  
Ulrich F. Schaefer ◽  
Karl-Heinz Kostka
Keyword(s):  
Human Skin ◽  
Skin Penetration ◽  
Flufenamic Acid ◽  
Skin Samples

In vitro and in vivo percutaneous absorption of 14C-chloroform in humans

1995 ◽  
Vol 14 (3) ◽  
pp. 260-265 ◽  
Author(s):  
D. Dick ◽  
Kme Ng ◽  
DN Sauder ◽  
I. Chu
Keyword(s):  
Human Skin ◽  
Percutaneous Absorption ◽  
Low Dose ◽  
Dermal Absorption ◽  
High Dose ◽  
Distilled Water ◽  
Applied Dose ◽  
Flow Through

Chloroform has been found in potable water and there is concern that significant dermal absorption may arise from daily bathing and other activities. The present study examines percutaneous absorption of 14C-chloroform in vivo using human volunteers and in vitro using fresh, excised human skin in a flow-through diffusion cell sys tem. Fifty microlitre doses of either 1000 μg ml-1 chloro form in distilled water, (16.1 μg cm-2) or 5000 μg ml-1 of chloroform in ethanol, (80.6 μg cm-1) were applied to the forearm of volunteers with exhaled air and urine being collected for analysis. Single doses of either 0.4 μg ml-1 chloroform in distilled water (low dose, 0.62 μg cm-2, 1.0 ml dosed) or 900 μg ml-1 chloroform in distilled water (high dose, 70.3 μg cm -2, 50 μl dosed) were applied to discs of the excised abdominal skin placed in flow-through dif fusion cells and perfused with Hepes buffered Hank's bal anced salt solution, with a wash at 4 h. In vivo absorption was 7.8 ± 1.4% (water as vehicle) and 1.6 ± 0.3% (ethanol as vehicle). Of the dose absorbed in vivo, more than 95% was excreted via the lungs (over 88% of which was CO2), and the maximum pulmonary excretion occurred between 15 min and 2 h after dosing. The percentage of dose absorbed in vitro (skin + perfusate) was 5.6 ± 2.7% (low dose) and 7.1 ± 1.4% (high dose). The above data demon strate that a significant amount of the dissolved chloro form penetrates through the human skin, and that a higher percentage of the applied dose was absorbed using water as vehicle. In addition, the in vitro method offers a good estimate for in vivo data.

scholarly journals Assessment of Vehicle Volatility and Deposition Layer Thickness in Skin Penetration Models

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 807
Author(s):  
Abdullah Hamadeh ◽  
John Troutman ◽  
Andrea N. Edginton
Keyword(s):  
Stratum Corneum ◽  
Goodness Of Fit ◽  
Skin Penetration ◽  
Dermal Absorption ◽  
Volatile Components ◽  
Specific Effects ◽  
Proposed Model ◽  
In Vitro Measurements

Systemic disposition of dermally applied chemicals is often formulation-dependent. Rapid evaporation of the vehicle can result in crystallization of active compounds, limiting their degree of skin penetration. In addition, the choice of vehicle can affect the permeant’s degree of penetration into the stratum corneum. The aim of this study is to build a predictive, mechanistic, dermal absorption model that accounts for vehicle-specific effects on the kinetics of permeant transport into skin. An existing skin penetration model is extended to explicitly include the effect of vehicle volatility over time. Using in vitro measurements of skin penetration by chemicals applied in both a saline and an ethanol solvent, the model is optimized to learn two vehicle-specific quantities: the solvent evaporation rate and the extent of permeant deposition into the upper stratum corneum immediately following application. The dermal disposition estimates of the trained model are subsequently compared against those of the original model using further in vitro measurements. The trained model showed a 1.5-fold improvement and a 19-fold improvement in overall goodness of fit among compounds tested in saline and ethanol solvents, respectively. The proposed model structure can thus form a basis for in vitro to in vivo extrapolations of dermal disposition for skin formulations containing volatile components.

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