title: Formulation of hydrogel-thickened nonionic microemulsions with enhanced percutaneous delivery of ibuprofen assessed in vivo in rats.
abstract: The study investigated usage of hydrogel of an anionic polymer xanthan gum for design of ibuprofen-loaded hydrogel-thickened microemulsions (HTMs) from the nonionic oil-in-water microemulsion (M). Xanthan gum demonstrated the performances of a thickening agent in physically stable HTMs at 5±3°C, 20±3°C, and 40±1°C during 6months. The results of physicochemical characterization (pH, conductivity, rheological behaviour, spreadability) indicated that HTMs containing 0.25-1.00% of the polymer had colloidal structure with oil nanodroplets of 14.34±0.98nm (PdI 0.220±0.075) dispersed in aqueous phase thickened with the polymer gel network which strength depended on the polymer concentration. HTMs with ibuprofen (5%) were evaluated as percutaneous drug delivery carriers. In vitro ibuprofen release from HTMs followed zero order kinetic (r>0.995) for 12h, while the referent hydrogel was described by Higuchi model. The HTM with optimized drug release rate and spreadability (HTM1) and the polymer-free microemulsion (M) were assessed and compared with the referent hydrogel in in vivo studies in rats. HTM1 and M were significantly more efficacious than reference hydrogel in producing antihyperalgesic and at lower extent antiedematous activity in prophylactic topical treatment protocol, whilst they were comparable in producing antihyperalgesic/antiedematous effects in therapeutic protocol. Topical treatments produced no obvious skin irritation.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: ljiljanadjek@gmail.com.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Djekic
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Martina
authors.initials: M
authors.lastname: Martinovic
authors.affiliation: Department of Pharmacology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Radica
authors.initials: R
authors.lastname: Stepanović-Petrović
authors.affiliation: Department of Pharmacology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Micov
authors.affiliation: Department of Pharmacology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Tomić
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Primorac
mesh_terms: D000287:Administration, Topical; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002351:Carrageenan; D065546:Drug Liberation; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D004655:Emulsions; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption; D023422:Skin Irritancy Tests
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D020100:Hydrogels; D002351:Carrageenan; D007052:Ibuprofen
keywords: Analgesic effect; Antiinflammatory activity; Hydrogel-thickened microemulsions; Ibuprofen; In vitro drug release; Xanthan gum