A comparison of in vitro skin-penetration cells

A new low-volume flow-through diffusion cell (LVFC) was designed to provide accurate determinations of penetrant flux across skin while minimizing the dilution of penetrant in receptor fluid and eliminating the need for magnetic stirring. The performance of the 0.3-mL LVFC was compared to a magnetically stirred, 4.3-mL high-volume flow cell (HVFC) and to a magnetically stirred, manually sampled 7.5-mL static cell (SC) with hydrophilic and lipophilic penetrants. The clearance of14C-labeled benzoic acid from the LVFC and HVFC followed an exponential profile expected for complete mixing when the LVFC and HVFC were run at flow rates of 0.4–0.9 and 4.0–5.2 mL/h, respectively. The in vitro dispositions of14C-labeled benzoic acid and estradiol were determined in the LVFC and HVFC by applying the compounds to split-thickness pig skin at a 4 μg/cm2dose. Additionally, the effects of receptor fluid flow rate (1.2 vs 3.5 cell volumes/h) and method of skin attachment (O-ring vs compression) were determined on disposition in the HVFC. The percutaneous penetration of benzoic acid and the residue of estradiol within skin did not differ between the LVFC and HVFC. However, the percutaneous penetration of benzoic acid increased significantly (p< 0.05) using the O-ring attachment as compared to compression at a flow rate of 1.2 cell volumes/h. The in vitro permeation of benzoic acid-saturated water and 17/β-estradiol-saturated propylene glycol monolaurate through human epidermis was compared between the LVFC, HVFC, and SC. The LVFC and HVFC had flow rates of 0.9–1.0 mL/h. The static cells were manually sampled; both receptor and donor chamber contents were replaced with fresh liquid at 8-h intervals. The flux profiles calculated from the output of the LVFC accurately represented those of the SC. The flux profiles calculated from the output of the HVFC were only comparable following correction for penetrant remaining in the cell. The clearance of benzoic acid, percutaneous penetration of benzoic acid, and penetration of estradiol into skin were similar in the LVFC and HVFC, but the LVFC was superior in requiring no magnetic stirring and approximately 1/15 the volume of receptor fluid. Additionally, skin-flux profiles from the LVFC output accurately represented those from the other cells, but without the inconvenience of manual sampling (SC) or correction of residual penetrant (HVFC).