title: 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 well-documented 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 non-polymeric 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.
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors: T C
authors: TC
authors: Beber
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors: D F
authors: DF
authors: Andrade
authors: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
authors: B
authors: B
authors: Kann
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors: M C
authors: MC
authors: Fontana
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors: K
authors: K
authors: Coradini
authors: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany; Helmholtz Centre for Infection Research, Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Delivery, Saabruecken, Germany.
authors: M
authors: M
authors: Windbergs
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: ruy.beck@ufrgs.br.
authors: R C R
authors: RC
authors: Beck
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D004655:Emulsions; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013499:Surface Properties; D034421:Sus scrofa; D014018:Tissue Distribution; D014732:Vibration
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005938:Glucocorticoids; D011108:Polymers; D003907:Dexamethasone
keywords: Dexamethasone; Skin delivery; Skin penetration; Skin permeation; Submicron particles; Vibrational spray-drying