Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection

Ungual formulations are regularly tested using human nails or animal surrogates in Franz diffusion cell experiments. Membranes sometimes less than 100 µm thick are used, disregarding the higher physiological thickness of human nails and possible fungal infection. In this study, bovine hoof membranes, healthy or infected with Trichophyton rubrum, underwent different imaging techniques highlighting that continuous pores traversed the entire membrane and infection resulted in fungal growth, both superficial, as well as in the membrane’s matrix. These membrane characteristics resulted in substantial differences in the permeation of the antifungal model substance bifonazole, depending on the dosage forms. Increasing the thickness of healthy membranes from 100 µm to 400 µm disproportionally reduced the permeated amount of bifonazole from the liquid and semisolid forms and allowed for a more pronounced assessment of the effects by excipients, such as urea as the permeation enhancer. Similarly, an infection of 400-µm membranes drastically increased the permeated amount. Therefore, the thickness and infection statuses of the membranes in the permeation experiments were essential for a differential readout, and standardized formulation-dependent experimental setups would be highly beneficial.

The Comparability of In Vitro and Ex Vivo Studies on the Percutaneous Permeation of Topical Formulations Containing Ibuprofen

In order to avoid in vivo experiments and to gain information about the suitability of surrogates for skin replacement, Franz-type diffusion cell experiments were conducted by using three ibuprofen-containing formulations (cream, gel and microgel) on bovine split-skin samples and cellophane membranes. Moreover, ex vivo examinations were performed on the isolated perfused bovine udder, to study the comparability of in vitro and ex vivo experimental set-ups. Depending on the formulation, noticeable differences in the permeation of Ibuprofen occurred in vitro (udder skin) and ex vivo (isolated perfused bovine udder), but not in the cellophane membrane. The rates of ibuprofen permeability (cream > gel > microgel) and adsorption into the skin (gel > microgel > cream) varied with the formulation, and were probably caused by differences in the ingredients. Furthermore, different storage conditions and seasonal variation in the collection of the skin samples probably led to differences in the amounts of ibuprofen adsorption apparent in the isolated bovine udder and udder skin. In vitro diffusion experiments should be preferred to experiments on isolated organs with regard to the costs involved, the throughput, and the intensity of labour required, unless metabolism of the drug in the skin, or cell–cell interactions are of particular interest.

Radionuclide Transport Modeling of Diffusion Cell Experiments Specific to a Backfill Barrier in a Salt Repository

ABSTRACTExperimental radionuclide migration diffusion cell data have been collected as part of the WIPP Waste Package Performance Program. This data was collected under conditions approximating geologic isolation of a backfill barrier in a salt repository. The experiments are designed to aid in the evaluation of engineered backfill barriers.This paper describes a radionuclide transport model designed to aid interpreting experimental diffusion cell migration data and eventually to simulate the long-term effectiveness of the backfill barrier in a salt repository. The model is designed to test a variety of expressions representative of potential mechanisms for retardation within the backfill for the best-fit with experimental data. From the comparison, the aim is to select the appropriate mechanism from the host of potential mechanisms for retardation. The model employs a novel integral equation approach to the solution of the transport equation with nonlinear retardation terms. The solution technique used in this model is a semi-analytical, iterative method for the general nonlinear problem. It is felt the technique offers improved computational efficiency over comparable finite difference methods.Comparisons between experimental migration diffusion cell data and the model predictions are presented in this paper. Tentative conclusions concerning the importance of the retardation mechanism to radionuclide transport in the backfill barrier will be drawn.