In vitro human skin concentrations following topical application of 2% tranexamic acid in co‐enhancer cream and branded cream formulations

Abstract

Background Melasma is a common pigmentary disorder that responds well to treatment with oral and/or locally injected tranexamic acid but less so to topical application. We hypothesized that this may be due to an inability of some topical formulations of tranexamic acid to achieve robust therapeutic concentrations at the viable epidermal target site in the skin. Aims To measure in vitro human epidermal and dermal skin concentrations of tranexamic acid following topical application of Fairence® T‐Complex, co‐enhancer cream and a Japanese branded cream control (“branded”) and compare these with estimates of tranexamic acid potency obtained from in vivo human pharmacokinetic and clinical studies and in vitro pharmacodynamic studies on inhibition of fibrinolysis. Methods Static vertical Franz cells and human abdominal skin were used to measure stratum corneum, viable epidermal, and dermal concentrations of tranexamic acid using HPLC‐MS‐MS analysis at 6 and 24 hour periods after topical application. Results Skin concentrations of tranexamic acid following application of the co‐enhancer cream were robustly within the concentration range estimated to be required for efficacy at both 6 and 24 hours. Those from the branded cream control were within the lower range at 24 hours. Conclusions These preclinical results support the benefits of conducting further studies, including a double‐blind placebo‐controlled clinical study, on Fairence® T‐Complex, co‐enhancer cream in patients with melasma. It is hypothesized that a more robust and timely clinical response may be achieved especially in refractory patients.

Reduction of enlarged facial pore using ion‐paired amino acid through enhancement in skin permeation and exfoliation: A placebo‐controlled in vivo study

“…The improvement of skin penetration efficacy is an essential factor in the skincare efficacy of cosmetics 33,34 . Previous studies reported that ion‐pairing with counter ions enhances the skin permeability by increased lipophilicity of a molecule 23,35 .…”

“…The improvement of skin penetration efficacy is an essential factor in the skincare efficacy of cosmetics. 33,34 Previous studies reported F I G U R E 1 Viscosity (A) and conductivity (B) changes in ion-pairing between serine and arginine at various molar ratios. Each sample was measured at 25°C.…”

Optimizing Melasma Management With Topical Tranexamic Acid: An Expert Consensus

“…It is hypothesized that a more robust and timely clinical response with this formulation may be achieved, especially in refractory patients. 18 An in vitro human skin penetration study shows that this formula significantly enhances the penetration of TXA into the skin vs regular TXA cream formula. It achieved an 11-fold increase in penetration of TXA to the targeted site vs the nonenhanced product (ie, at 24 hours, this TXA formulation achieved a concentration of 43.9 µg/mL vs 3.9 µg/mL at the epidermis, and 1.57 µg/mL vs 0.14 µg/mL at the dermis, respectively).…”

“…It achieved an 11-fold increase in penetration of TXA to the targeted site vs the nonenhanced product (ie, at 24 hours, this TXA formulation achieved a concentration of 43.9 µg/mL vs 3.9 µg/mL at the epidermis, and 1.57 µg/mL vs 0.14 µg/mL at the dermis, respectively). 18 This formulation tended to reach similar peak plasma levels as orally administered TXA based on pharmacokinetic study results (ie, maximal inhibitory concentration values of TXA fibrinolytic activity are <20.0 μg/mL or within the epidermal concentration range). 18 Clinical studies have demonstrated a significant reduction in the melasma area and severity index (MASI) of 37% compared with baseline and improvement in skin clarity in both pigmented and normal skin.…”

Combining Raman imaging and MCR‐ALS analysis for monitoring retinol permeation in human skin

“…(ii) Franz cell (diffusion cell) consists of a donor compartment (chamber for drug or active application), a fragment of skin or a membrane simulating skin within which the drug or active may diffuse, and an acceptor chamber containing an appropriate dosage solution from which molecules of interest can be quantified. [16][17][18][19] The passage kinetics is determined by dosing the active substance, at regular intervals, in the acceptor compartment. It is used for toxicity screening or quality control.…”