Mechanism of Ion-Pair Strategy in Modulating Skin Permeability of Zaltoprofen: Insight from Molecular-Level Resolution Based on Molecular Modeling and Confocal Laser Scanning Microscopy

Cui, Hongxia; Quan, Peng; Zhao, Hanqing; Wen, Xu; Song, Wenting; Xiao, Yi; Zhao, Yahui; Fang, Liang

doi:10.1002/jps.24543

Cited by 27 publications

(26 citation statements)

References 37 publications

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“…Skin preparation and barrier integrity inspection were conducted according to the method reported in our previous studies (Cui et al, 2015). Modified two-chamber diffusion cells were used as the permeation apparatus, which had a cell capacity of 3 mL and an effective diffusion area of 0.95 cm 2 .…”

Section: In Vitro Permeation Studiesmentioning

confidence: 99%

“…All the mice were shaved on the abdomen for an area of 5 cm 2 one day before the experiments. On the day of the experiment, the barrier integrity of the skin was first inspected according to the method reported in our previous study (Cui et al, 2015). Those mice with defective skin were rejected in the assessment of analgesic effect.…”

Section: Analgesic Effect Assessmentmentioning

confidence: 99%

“…Our previous studies showed that the skin permeability of ZAL could be modulated by an ion-pair interaction with organic amines (Cui et al, 2015). Accordingly, various ZAL ion-pair complexes were synthesized and investigated for the transdermal patch system of ZAL.…”

Section: Characterization Of Zal Ion-pair Complexesmentioning

confidence: 99%

“…As a general rule, a proper candidate for passive skin delivery should have certain physicochemical properties, such as low molecular weight (MW5500 Da), low melting point (mp5200 C), and moderate lipophilicity (log K o/w ¼ 1-3) (Chen & Gao, 2016). The physicochemical properties of ZAL (MW ¼ 298.36 Da, C, data were obtained from the Merck Index; log K o/w ¼ 2.57 (Cui et al, 2015)) imply that it is a potential permeant suitable for TDDS.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that an ion pair behaves as one unit in determining the penetration behavior. By varying counter ions, the ion pair interaction has a direct effect on the physicochemical properties of permeants, such as solubility (Cheong & Choi, 2002), lipophilicity (Fang et al, 2003), conductivity (Hatanaka et al, 2000), melting point (Dimas et al, 2005), and hydrogen bonding potential (Cui et al, 2015). The diversity is beneficial to a flexible formulation design.…”

Section: Introductionmentioning

confidence: 99%

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Development of a drug-in-adhesive patch combining ion pair and chemical enhancer strategy for transdermal delivery of zaltoprofen: pharmacokinetic, pharmacodynamic and in vitro/in vivo correlation evaluation

et al. 2016

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The aim of the study was to develop a drug-in-adhesive patch system for transdermal delivery of zaltoprofen (ZAL). The formulation was designed in combination with the ion pair and chemical enhancer strategy. Seven organic amines were chosen as counter ions, and the prepared ion pairs were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The in vivo pharmacokinetic performance of ZAL was studied on rabbits following transdermal and intravenous administration. A deconvolution method was applied to determine the correlation between the in vitro permeation and the in vivo absorption. Acetic acid-induced writhing response was conducted on mice to evaluate the analgesic effect. In vitro permeation results showed that both ion pairs and chemical enhancers were effective in modulating ZAL skin permeation from patches. The enhancement ratio was negatively correlated to the polar surface area (PSA) of counter ions, and was positively correlated to the octanol-water partition coefficient (log K o/w ) of chemical enhancers, respectively. The optimized formulation contained 10% (w/w) ZAL-triethylamine and 10% (w/w) isopropyl myristate, with DURO-TAK Õ 87-4098 as the pressure sensitive adhesive matrix. Furthermore, the in vitro permeation data were well correlated with the in vivo absorption data. The analgesic effect of the optimized patch was comparable to the commercial indometacin plasters. In conclusion, it was feasible for transdermal delivery of ZAL by the synergistic action of ion pair and chemical enhancer, and the in vitro permeation data were indicative of the in vivo performance for the developed patches. KeywordsIon pair, in vitro/in vivo correlation, pharmacokinetic, transdermal, zaltoprofen History

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Section: In Vitro Permeation Studiesmentioning

confidence: 99%

Section: Analgesic Effect Assessmentmentioning

confidence: 99%

Section: Characterization Of Zal Ion-pair Complexesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%