Submicron polymeric particles prepared by vibrational spray-drying: Semisolid formulation and skin penetration/permeation studies

Abstract

Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present welldocumented side effects and their delivery to the skin is often insufficient.Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing nonpolymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time.Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX.

Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing

“…Recovery rates of ~ 4% DXM after 12 h incubation were found (Fig. 6B), similar to DXM recovery after topical application in submicron polycaprolactone particles shown by Beber and coworkers [66]. In contrast however, this work lacked a comparison to a benchmark therapy and used the infinite dose approach, which does not reflect the clinical use.…”

Redispersible spray-dried lipid-core nanocapsules intended for oral delivery: the influence of the particle number on redispersibility

“…This technique has been used to analyze different carrier systems, ranging from solid dispersion and tablets up to drug-eluting coatings and polymeric microparticles (Smith et al 2015). It has been successfully used for visualizing dexamethasone homogeneous distribution in submicron polymeric particles (Beber et al 2014), and for chemically selective visualization of particle uptake into human buccal epithelial cells (Kann et al 2014). In this study, CRM enabled the visualization of the spatial distribution of the different compounds (chemically selective and spatially resolved) in the spray-dried powders, affording to better understand the influence of the particle number density of the fed sample on the redispersion behavior of such powders.…”

Liquid chromatography method to assay tretinoin in skin layers: validation and application in skin penetration/retention studies

“…After removing excess formulation on the skin membrane with cotton pieces, the stratum corneum was removed by the tape stripping technique using 18 tapes (3M, Durex™), as described by Beber et al [34]. Each tape was pressed onto the membrane and then rubbed with a spatula to remove the stratum corneum.…”