title: Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design.
abstract: We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles - high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50°C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant - polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances.
authors.forename: Tanja
authors.initials: T
authors.lastname: Isailović
authors.forename: Sanela
authors.initials: S
authors.lastname: Ðorđević
authors.forename: Bojan
authors.initials: B
authors.lastname: Marković
authors.forename: Danijela
authors.initials: D
authors.lastname: Ranđelović
authors.forename: Nebojša
authors.initials: N
authors.lastname: Cekić
authors.forename: Milica
authors.initials: M
authors.lastname: Lukić
authors.forename: Ivana
authors.initials: I
authors.lastname: Pantelić
authors.forename: Rolf
authors.initials: R
authors.lastname: Daniels
authors.forename: Snežana
authors.initials: S
authors.lastname: Savić
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005260:Female; D006801:Humans; D007509:Irritants; D049329:Nanostructures; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D012869:Skin Absorption / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D004655:Emulsions; D007509:Irritants; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D004008:Diclofenac; C056498:aceclofenac