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

Abstract

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

Intra-articular delivery of flurbiprofen sustained release thermogel: improved therapeutic outcome of collagenase II-induced rat knee osteoarthritis

“…Flurbiprofen belongs to a propionic acid class of NSAIDs. The carboxyl group and the fluorine atom in the structure as proton donors and acceptors could interact with the copolymer by hydrogen bonding interaction (Qiao et al., 2005 ; Cui et al., 2016 ). Thus, an increase in the copolymer concentration in the hydrogel increased the interaction with the drug molecular, which contributed to a relatively steady drug release rate (Gao et al., 2011 ; Cui et al., 2015 ).…”

Reported estimation techniques for quantification of zaltoprofen: A review

“…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 [7].…”

“…This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit [7]uril (CB [7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction.…”

“…UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB [7] contents suggested the addition of β-CD or CB [7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB [7] could efficiently shorten the disintegrating time.…”

A Comparative Evaluation of Anti-Inflammatory and Arthritic Effects of bradykinin inhibitor Zaltoprofen over Piroxicam in Murine models: A randomized experimental study.

“…Santenna C et al concluded that zaltoprofen analgesic e cacy was non-inferior to a standard NSAID piroxicam in experimental murine models of acute pain [5]. A multicentric, double-blind, double-dummy, randomized, parallel-group comparative study by Pareek et.al concluded that clinically zaltoprofen is non-inferior to Diclofenac [11]. Akihico T et al, had shown that zaltoprofen might be a potential agent to act against malignant phenotypes in chondrosarcomas via activation of PPAR γ and inhibition of MMP 2 activity [12].…”