Skin Permeation Data Research Articles

Percutaneous Penetration of Drugs: A Quantitative Structure–Permeability Relationship Study

Human skin permeation data taken from the literature were analyzed for quantitative relationships with physicochemical properties and structural descriptors. No correlations exist with molecular weights and solvent-accessible surface areas. In most cases, skin permeation was inversely correlated with the parameter ∆log Poct-hep (i.e., log Poctanol minus log Pheptane), which is mainly a measure of the H-bond donor acidity of the solutes. Lipophilicity itself, as expressed by log Poctanol, also contributes positively to skin permeation in some cases. The results of this quantitative structure–permeability relationship study are interpreted in terms of a unified mechanistic model whereby drugs can permeate via an intercellular route (correlation with both ∆log Poct-hep and log Poct) and/or a transcellular route (correlation with log Poct only).

カプリル酸モノグリセリドならび塩酸ドパミンを含有したテープ剤の有用性

Several tape formulations containing a possible drug, dopamine hydrochloride and a useful penetration-enhancer, glyceryl monocaprylate were prepared, and the release rate and skin permeation rate were measured. Skin permeation was measured in vitro by using the excised hairless rat skin and diffusion cell. Release rate from the drug-suspended adhesive was rapider than that from the drug-dissolved one. Acrylvinyl-type adhesive showed the best skin permeation of the drug among the adhesives tested in the present study. The higher were the drug concentration and enhancer concentration, the higher was the skin permeation. The blood concentration after application the formulation could be predicted by the in vitro skin permeation data and elimination pharmacokinetics.

Estimation of blood concentration of drugs after topical application from in vitro skin permeation data. II. Approach by using diffusion model and compartment model.

In order to estimate the in vivo behavior (e.g., blood concentration) of drugs on percutaneous absorption from in vitro permeation data using excised skin and pharmacokinetic parameters at intravenous administration, two models, a diffusion model and a compartment model with or without shunt transport, were established and applied to the in vitro and in vivo skin permeation data of nicorandil in hairless rats. When water was employed as a donor solvent (water treatment), the plasma concentration-time curve, which was calculated by means of the diffusion model, was similar to the observed values without introduction of shunt transport. In the case of propylene glycol treatment, on the other hand, the calculated plasma levels were not necessarily similar to the observed values, but it was found that the calculated values were better fitted to the observed values by introduction of shunt transport in the in vitro skin diffusion model. Similar results were obtained with the compartment model. These results suggest that both models may be useful to predict the plasma concentration after application of topical formulations. The characteristics and usefulness of these models were compared with those of the previously reported convolution method.

Estimation of blood concentration of drugs after topical application from in vitro skin permeation data. I. Prediction by convolution and confirmation by deconvolution.

Estimation of blood concentration of drugs after topical application from in vitro skin permeation data. I. Prediction by convolution and confirmation by deconvolution.

Transdermal delivery of anxiolytics: in vitro skin permeation of midazolam maleate and diazepam

The skin permeation profiles of midazolam maleate and diazepam from various solvent systems were investigated. Results were computed using a program designed to manipulate skin permeation data. It was shown that the permeation rates of diazepam and midazolam maleate may be affected by using aqueous mixtures of polar organic solvents. The effect of 1% and 5% Azone on the permeation of diazepam and midazolam maleate was studied. It was found that Azone increases the permeation fluxes of both drugs, the hydrophobic diazepam and the salt midazolam maleate. In the presence of 5% Azone in a solvent system of propylene glycol (PG-ETH-H 2O) the fluxes were increased 43 times for diazepam and 86 times for midazolam maleate. The performance of a novel hydrophilic transdermal matrix containing 50 mg midazolam maleate was tested in vitro. The steady-state flux obtained was used for a coarse estimation of the feasibility of transdermal administration of midazolam maleate.