title: Design and Evaluation of a Novel Felbinac Transdermal Patch: Combining Ion-Pair and Chemical Enhancer Strategy.
abstract: The aim of this study was to design a novel felbinac (FEL) patch with significantly higher (P < 0.05) skin permeation amount than the commercial product SELTOUCH® using ion-pair and chemical enhancer strategy, overcoming the disadvantage of the large application area of SELTOUCH®. Six complexes of FEL with organic amines diethylamine (DEA), triethylamine (TEA), N-(2'-hydroxy-ethanol)-piperdine (HEPP), monoethanolamine (MEtA), diethanolamine (DEtA), and triethanolamine (TEtA) were prepared by ion-pair interaction, and their formation were confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), infared spectroscopy (IR), and proton nuclear magnetic resonance spectroscopy ((1)H-NMR). Subsequently, the effect of ion-pair complexes and chemical enhancers were investigated through in vitro and in vivo experiments using rabbit abdominal skin. Results showed that FEL-TEA was the most potential candidate both in isopropyl palmitate (IPP) solution and transdermal patches. Combining use of 10% N-dodecylazepan-2-one (Azone), the optimized FEL-TEA patch achieved a flux of 18.29 ± 2.59 μg/cm(2)/h, which was twice the amount of the product SELTOUCH® (J = 9.18 ± 1.26 μg/cm(2)/h). Similarly, the area under the concentration curve from time 0 to time t (AUC0-t ) in FEL-TEA patch group (15.94 ± 3.58 h.μg/mL) was also twice as that in SELTOUCH® group (7.31 ± 1.16 h.μg/mL). Furthermore, the in vitro skin permeation results of FEL-TEA patch was found to have a good correlation with the in vivo absorption results in rabbit. These findings indicated that a combination of ion-pair and chemical enhancer strategy could be useful in developing a novel transdermal patch of FEL.
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China. fangliang2003@yahoo.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000279:Administration, Cutaneous; D000588:Amines / Q000737:chemistry; D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010539:Permeability; D010648:Phenylacetates / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D057968:Transdermal Patch; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000588:Amines; D010648:Phenylacetates; C012776:biphenylylacetic acid
keywords: chemical enhancer; felbinac-triethylamine (FEL-TEA); in vitro/in vivo correlation (IVIVC); ion-pair; transdermal patch