Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance

Abstract

To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09μg/cm(2), and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.

Prolonged skin retention of clobetasol propionate by bio-based microemulsions: a potential tool for scalp psoriasis treatment

“…However, in the case of ME1 a stronger interaction between water and surfactant at the interface can be hypothesized, this causes the freezing point to move to very low temperatures (-60°C), although with minor intensity, due to a lower water content than ME2. This water behaviour has been already found for W/O MEs in previous works [31,40]. By comparing the curves of the single components (data not shown), a characteristic peak for ME1 (around -40°C) attributed to olive oil can be also observed.…”

“…Overview images showed distinct ME droplets with spherical shape and a good size homogeneity (Supplementary Figure S3b,c) which can be clearly attributed to the W/O systems herein developed. In this case, we did not report images of drug loaded formulations since it has been already demonstrated that the addition of the drug did not significantly influence the vehicles nanostructure [31]. This assumption is also in accordance to most of experimental parameters above reported.…”

“…An empty sealed aluminium pan was used as reference. DSC curves were generated by cooling the samples from 25°C to -100°C (cooling rate 10°C/min) in a nitrogen atmosphere with a flow rate of 40 ml/min [30,31].…”

Microemulsion Microstructure(s): A Tutorial Review

“…Additionally, w/o µEs are particularly interesting for oral protein delivery due to their increased oral bioavailability through the gastrointestinal tract and their protection capacity [ 144 ]. A large number of drugs, such as antibiotics [ 141 , 142 , 143 , 144 , 145 , 146 ], antifungals [ 147 , 148 , 149 ], anti-inflammatory [ 150 , 151 , 152 , 153 , 154 ] and immunosuppressive [ 155 ] molecules have been used in μEs systems.…”

Topical and cutaneous delivery using nanosystems

“…There is less concern over colloidal nanosystems such as emulsions and lipid-based materials because these are likely to be biodegradable on application to the skin, although the molecular products will still be assessed in the usual way for irritancy and cytotoxicity. For example, Todosijević et al [193] used changes in erythema index, skin hydration and TEWL to assess the skin…”