In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems

Abstract

Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P < 0.001) higher than that with product-C, product-A, gel, and spray. However, products-A and C, gel, and spray showed almost the same (P > 0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P < 0.001) higher than those with products-A and B, gel, and spray. The in vitro study results indicate a high potential of skin-to-skin drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases

“…For the release studies, a synthetic cellulose membrane (molecular cut-off weight of 10,000 Da) was interposed between the two compartments. Throughout investigations, sink conditions were maintained, the fluid receptor was constantly stirred with a small magnetic stirring bar, and the temperature was maintained at 32.0 ± 0.5 • C by means of a circulating water bath [28]. The duration of experiments was 24 h and at specific time intervals, 500 µL of the receptor phase was collected for HPLC (see Section 2.9) determination of the released sulforaphane.…”

“…At prefixed intervals, for all 24 h of the experiments, aliquots of the receptor phase were withdrawn and immediately analyzed by HPLC (see Section 2.9) to determine the amount of permeated sulforaphane. Additionally, in this case, the withdrawn volume was replaced with the same amount of fresh solution and the temperature was maintained at 32.0 ± 0.5 • C by means of a circulating water bath [28].…”

Assessing The Risk of Transfer of a Transdermal Hormonal Drug Through Skin-To-Skin Contact by an In Vitro Permeation Testing Method

“…A reversed-phase HPLC method, adopted from literature, was used for the analysis of testosterone [23] and estradiol [24] contents in skin and receiver medium samples. Both methods were validated as per ICH Q2(R1) guidelines for specificity, linearity, accuracy, precision, range, limit of quantitation (LOQ), limit of detection (LOD) and system suitability [25].…”