Comparison of the In Vitro and Ex Vivo Permeation of Existing Topical Formulations Used in the Treatment of Facial Angiofibroma and Characterization of the Variations Observed

Abstract

Rapamycin has been used topically to treat facial angiofibromas associated with tuberous sclerosis for more than a decade. In the absence of a commercial form, a large number of formulations have been clinically tested. However, given the great heterogeneity of these studies, particularly with regard to the response criteria, it was difficult to know the impact and thus to compare the relevance of the formulations used. The objective of this work was therefore to evaluate the link between the diffusion of rapamycin and the physico-chemical characteristics of these different formulations on Strat-M® membranes as well as on human skin using Franz cells. Our results underline the importance of the type of vehicle used (hydrogel > cream > lipophilic ointment), the soluble state of rapamycin and its concentration close to saturation to ensure maximum thermodynamic activity. Thus, this is the first time that a comparative study of the different rapamycin formulations identified in the literature for the management of facial angiofibromas has been carried out using a pharmaceutical and biopharmaceutical approach. It highlights the important parameters to be considered in the development and optimization of topical rapamycin formulations with regard to cutaneous absorption for clinical efficacy.

Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells

“…In the case of IVPT, to analyze data, QT amount permeated (μg/cm 2 ) was plotted as a function of time. Fick’s law was considered since it describes the steady-state permeation through the skin, assuming that, under sink conditions, drug concentration in the receptor compartment is negligible with respect to that in the donor compartment [ 35 ]. The steady-state flux of drug per unit area “Jss” is described as: Jss = P × Cd × D/e where P is the partition coefficient, Cd is the drug concentration in the donor compartment, D is QT diffusion coefficient, and e is the thickness given by the supplier or measured.…”

Mixed Polymeric Micelles for Rapamycin Skin Delivery

“…Samples were analyzed using the HPLC method to determine the amount of rapamycin diffused. The steady state flux at 24 h, in vitro skin permeation steady state flux (Jss) (µg cm −2 h −1 ), was determined by measuring the slope from the plot of the cumulative amount permeated versus time [ 11 ].…”

“…The epidermis was subsequently separated from the dermis, and each compartment was cut into small pieces and soaked in methanol for 12 h with continuous stirring at room temperature. The extraction procedure was validated in our previous study (data not shown) [ 11 ]. The extraction skin samples were then centrifuged at 10,000 rpm for 15 min and analyzed by HPLC.…”

“…However, the efficacy endpoints, duration of treatment, types of formulations and concentrations tested were heterogeneous, making it difficult to compare these studies [ 6 ]. A study has identified different formulations to compare their performance in terms of permeation [ 11 ]. The results showed the influence of the vehicle and the thermodynamic activity on the cutaneous bioavailability of rapamycin.…”

Fabrication and Appraisal of Simvastatin via Tailored Niosomal Nanovesicles for Transdermal Delivery Enhancement: In Vitro and In Vivo Assessment

“…The permeation coefficient (Kp; the speed of the drug track across the membrane in cm/h) was computed with the equation Kp = Jss/Co, where Jss is the flux and Co is the donor solution concentration [ 47 ]. The diffusion coefficient (D) was calculated from the lag time (Tlag) with the following equation [ 48 ]: where e was the thickness, controlled and given by the supplier (thickness 5 mm).…”