Stratum corneum absorption kinetics of 2 potent topical corticosteroid formulations: a pilot study.

Fluocinonide and halcinonide are class II topical corticosteroids that are indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and generally are applied to affected skin at least twice daily. This pilot study compared the absorption kinetics of cream formulations of fluocinonide and halcinonide in the stratum corneum within a 9-hour period following application. A dermal tape-stripping protocol was used to quantify corticosteroid concentration at 6 sequential depths in the skin of 4 sites on the forearm. Halcinonide and fluocinonide were extracted from the strips and concentrations were measured using liquid chromatography-mass spectrometry. Results demonstrated the immediate absorption of fluocinonide and halcinonide into the stratum corneum within 1 hour of application followed by a sustained release of halcinonide and a steady decline of fluocinonide after peaking.

Effect of concentration and degree of saturation of topical fluocinonide formulations on in vitro membrane transport and in vivo availability on human skin.

PURPOSE: The thermodynamic activity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. METHODS: Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. RESULTS: Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. CONCLUSIONS: From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.

Absorption of a topical steroid and evaluation of adrenal suppression in patients with erosive lichen planus.

This study was designed to investigate the absorption of a topical steroid applied to the gingiva and buccal mucosa of patients with erosive lichen planus and to healthy control patients. In addition, adrenal suppression was assessed by measurements of serum and urine cortisol levels. Ten patients with erosive lichen planus and eight control patients provided urine and blood samples at baseline, day 3, and day 21. After establishment of baseline laboratory values, patients were instructed to apply 500 mg of a 0.05% fluocinonide gel to the gingiva and buccal mucosa three times a day for 3 weeks. Measurements of cortisol levels revealed no significant changes in either the disease or the control group. Although procedures were developed to detect fluocinonide, none of the patients showed evidence of the steroid during the study. It was concluded that the topical application of a fluocinonide gel to the gingiva and buccal mucosa over a 3-week period in patients with erosive lichen planus produced no adrenal suppression.

Topical corticosteroid compounding: effects on physicochemical stability and skin penetration rate.

Compounding compatibility studies of four corticosteroid cream products and four commonly added chemicals are presented. Physical alteration, chemical stability, micropreservative challenge status, and in vitro skin penetration were evaluated at ambient conditions for 2 months. The study was designed to generate useful, previously unavailable information to aid dispensing pharmacists and dermatologists.