title: Design of Block Copolymer Costabilized Nonionic Microemulsions and Their In Vitro and In Vivo Assessment as Carriers for Sustained Regional Delivery of Ibuprofen via Topical Administration.
abstract: Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-in-water microemulsions with Newtonian flow behavior, low viscosity (from 368 ± 38 to 916 ± 46 mPa s), and average droplet size from 14.79 ± 0.31 to 16.54 ± 0.75 nm. Ibuprofen in vitro release from the microemulsions was in accordance with zero-order kinetics (R0(2) > 0.99) for at least 12 h. The maximum drug release rate (3.55%h(-1) ) was from the microemulsion M3 comprising 16%, w/w of poloxamer 407. The release rate of ibuprofen from the reference hydrogel followed Higuchi kinetics (RH(2) > 0.99), and drug amount released after the 6th hour was negligible. In a rat model of inflammation, the microemulsion M3 was significantly more efficacious than the reference hydrogel in exerting antihyperalgesic effects in prophylactic topical treatment, whereas they were comparable in therapeutic treatment as well as in producing antiedematous effect in both protocols. No obvious skin irritation was observed in in vivo studies. The developed nonionic surfactants-based microemulsions containing the optimal concentration of poloxamer 407 could be promising carriers for sustained regional delivery of ibuprofen via topical administration.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Djekic
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia.
authors.forename: Martina
authors.initials: M
authors.lastname: Martinovic
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia.
authors.forename: Radica
authors.initials: R
authors.lastname: Stepanović-Petrović
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Tomić
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Micov
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Primorac
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D004339:Drug Compounding; D004355:Drug Stability; D004487:Edema / Q000276:immunology / Q000517:prevention & control; D004655:Emulsions; D005079:Excipients / Q000009:adverse effects / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D049329:Nanostructures / Q000009:adverse effects / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry*; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000276:immunology; D012995:Solubility; D013501:Surface-Active Agents / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D007052:Ibuprofen
keywords: biocompatibility; controlled release; drug delivery systems; light scattering (dynamic); microemulsion; nanotechnology; physicochemical properties; polymers; skin