Microemulsions based on TPGS and isostearic acid for imiquimod formulation and skin delivery.

Autor: Pescina S; Food and Drug Department, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy., Garrastazu G; Faculdade de Farmácia, Universidade da Região da Campanha, URCAMP, Brazil., Del Favero E; Department of Medical Biotechnologies and Translational Medicine, LITA, University of Milan, Segrate, Italy., Rondelli V; Department of Medical Biotechnologies and Translational Medicine, LITA, University of Milan, Segrate, Italy., Cantù L; Department of Medical Biotechnologies and Translational Medicine, LITA, University of Milan, Segrate, Italy., Padula C; Food and Drug Department, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy., Santi P; Food and Drug Department, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy., Nicoli S; Food and Drug Department, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy. Electronic address: sara.nicoli@unipr.it.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2018 Dec 01; Vol. 125, pp. 223-231. Date of Electronic Publication: 2018 Oct 11.
DOI: 10.1016/j.ejps.2018.10.007
Abstrakt: Imiquimod (IMQ) is an immunostimulant drug topically used for the treatment of actinic keratosis and basal cell carcinoma. IMQ formulation and skin delivery is difficult because of its very low solubility in the most of pharmaceutical excipients and very poor skin penetration properties. The purpose of this study was to develop a microemulsion to optimize imiquimod skin delivery using d‑α‑tocopherol polyethylene glycol-1000 succinate (TPGS) as surfactant (so as to take advantage of its thickening properties) and isostearic acid as oil phase. This fatty acid was selected since it has demonstrated a good solubilizing power for imiquimod and it has also shown to contribute to its therapeutic activity. We have built pseudo-ternary diagrams using two different co-surfactants (Transcutol® and propylene glycol - PG) in a 1:1 ratio with TPGS and then selected microemulsions in the clear and viscous regions of the diagrams. The systems were characterized in terms of rheology and X-ray scattering; additionally, the capability to promote IMQ skin uptake was evaluated ex-vivo on a porcine skin model. All the formulations selected in the gel-microemulsion regions behaved as viscoelastic solids; X-rays scattering experiments revealed in all cases the presence of an ordered lamellar structure, but with differences in terms of interlamellar distance and flexibility between Transcutol® and PG-containing systems. A higher flexibility and a greater hydrophobic volume, possibly interconnected at some point, was associated to the use of Transcutol® and had an impact on the microemulsion capacity to solubilize IMQ as well as on the capability to enhance drug uptake into the skin. The best performing gel-like microemulsion was composed of ≈26% of water, ≈21% of isostearic acid, ≈26% of TPGS and ≈27% of Transcutol® and accumulated, after 6 h of contact, 3.0 ± 1.1 μg/cm 2 of IMQ. This value is higher than the one reported in the literature for the commercial cream (1.9 ± 0.8 μg/cm 2 ), despite the 4-times lower concentration of the vehicle (13 mg/g for the microemulsion vs 50 mg/g for the commercial cream).
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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