Sucrose esters as biocompatible surfactants for penetration enhancement: An insight into the mechanism of penetration enhancement studied using stratumcorneum model lipids and Langmuir monolayers.

Up to now, the molecular mechanism of the penetration enhancing effect of sucrose esters (SEs) on stratumcorneum (SC) has not been explained in details. In this study, variety of surface sensitive techniques, including surface pressure-area (π-A) isotherms, infrared reflection-absorption spectroscopy (IRRAS), and Brewster angle microscopy (BAM), have been used to investigate interactions between SEs and SC intercellular lipids. A monolayer of the mixture of ceramide AS C18:18, stearic acid and cholesterol in the molar ratio of 1:1:0.7 on an aqueous subphase is a good model to mimic a single layer of intercellular SC lipids. The π-A isotherms of mixed monolayers and parameters derived from the curves demonstrated the interaction between nonionic surfactants such as SEs and SC lipids. With increasing SE concentration, the resultant monolayer films became more fluid and better compressible. IRRAS measurements showed that SEs disordered the acyl chains of SC lipids, and the BAM images demonstrated the modification of the domain structures in SC monolayers. Longer chain-SE has a stronger disordering effect and is better miscible with ceramides in comparison to SE with a shorter hydrophobic part. In conclusion, this study demonstrates the disordering effect of SEs on the biomimetic SC model, pointing out that small changes in the structure of surfactant may have a strong influence on a penetration enhancement of lipophilic drugs through intercellular lipids of skin.

Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance.

Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth- 7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.

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

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.