The relationship between hydrogen-bonded ion-pair stability and transdermal penetration of lornoxicam with organic amines

Xi, Honglei; Wang, Zhongyan; Chen, Yang; Li, Wei; Sun, Lixin; Fang, Liang

doi:10.1016/j.ejps.2012.04.017

Cited by 26 publications

(25 citation statements)

References 25 publications

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“…The acidity of organic acid was also an important factor affecting the permeability of ESP ion-pairs. Xi et al had demonstrated that the larger pK a difference between the amine and acid, the more stable ion-pair complexes were and that led to a higher flux of Lornoxicam (18). Similarly, in our study, the stronger acidity of organic acids, the better control effect of ESP-acid complexes.…”

Section: Discussionsupporting

confidence: 61%

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Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

et al. 2016

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Abstract. In order to regulate the skin permeation rate (flux) of escitalopram (ESP), ion-pair strategy was used in our work. Five organic acids with different physicochemical properties, benzoic acid (BA), ibuprofen (IB), salicylic acid (SA), benzenesulfonic acid (BSA), and p-aminobenzoic acid (PABA), were employed as counter-ions to regulate the permeation rate of ESP across the rabbit abdominal skin in vitro. The interaction between ESP and organic acids was characterized by FTIR and 13 C NMR spectroscopy. Results showed that all organic acids investigated in this study performed a controlling effect on ESP flux. To further analyze the factors concerned with the permeation capability of ESP-acid complex, a multiple linear regression model was used. It is concluded that the steady-state flux (J) of ESP-acid complexes had a positive correlation with log K o/w (the n-octanol/water partition coefficient of ion-pair complex) and pK a (the acidity of organic acid counter-ion), but a negative correlation with MW (the molecular weight of ionpair complex). The logK o/w of ion-pair complex is the primary one in all the factors that influence the skin permeation rate of ESP. The results demonstrated that organic acid with appropriate physicochemical properties can be considered as suitable candidate for the transdermal drug delivery of escitalopram.

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Section: Discussionsupporting

confidence: 61%

“…IPP is a lipophilic solvent with low dielectric constant (ε = 3.18), which is frequently used in the study of transdermal drug delivery. The permeation experiment from IPP ignored the complicated influence of patch matrix, thus, the flux from IPP can be regarded as an indicator of drug skin permeability (18).…”

Section: Discussionmentioning

confidence: 99%

Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

et al. 2016

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“…This explanation also conformed to the proton-transfer model of Huyskens and Zeegers-Huyskens [27], which showed that the larger pKa difference between the proton donor (FEL) and acceptor NMR spectroscopy also offered a good evidence for hydrogen bonding and was therefore used to analyze the interaction between FEL and organic amines in IPP, based on the chemical shift change of the methenyl proton near the carboxyl group. However, the complicated structure of IPP interfered the spectra of samples, deuterated chloroform (ε r =4.81) was chosen as substitutions of IPP (ε r =3.18) based on its comparable dielectric constant [23]. As illustrated in Table I, the signal of the methenyl proton in all complexes brought out upfield shifts compared with that in FEL.…”

Section: Ir and 1 H-nmr Characterizationmentioning

confidence: 99%

“…As the carboxylic acid groups in FEL can form dimers by the intermolecular hydrogen bonding [24], the R 3 -N acceptor groups in DEA and TEA might disrupt the original intermolecular hydrogen bond due to the formation of new intermolecular hydrogen bond with the carboxyl donor groups in FEL. Based on literatures [25], it could be inferred that the electronegativity of R 3 -N acceptor groups in DEA and TEA were weaker than that of C=O acceptor groups in FEL, thus leading to the electron redistribution of the corresponding carboxyl group acted as a donor group and the blue shift of C=O stretching vibration in this group [23,26]. This explanation also conformed to the proton-transfer model of Huyskens and Zeegers-Huyskens [27], which showed that the larger pKa difference between the proton donor (FEL) and acceptor NMR spectroscopy also offered a good evidence for hydrogen bonding and was therefore used to analyze the interaction between FEL and organic amines in IPP, based on the chemical shift change of the methenyl proton near the carboxyl group.…”

Section: Ir and 1 H-nmr Characterizationmentioning

confidence: 99%

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Design and Evaluation of a Novel Felbinac Transdermal Patch: Combining Ion-Pair and Chemical Enhancer Strategy

Liu

Song

et al. 2015

AAPS PharmSciTech

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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′-hydroxyethanol)-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 (AUC 0-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.KEY WORDS: chemical enhancer; felbinac-triethylamine (FEL-TEA); in vitro/in vivo correlation (IVIVC); ion-pair; transdermal patch.

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Ion Pairing for Controlling Drug Delivery

Giovagnoli

Schoubben

Róssi

2016

Drug Delivery Systems for Tuberculosis Prevention and Treatment

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The relationship between hydrogen-bonded ion-pair stability and transdermal penetration of lornoxicam with organic amines

Cited by 26 publications

References 25 publications

Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

Design and Evaluation of a Novel Felbinac Transdermal Patch: Combining Ion-Pair and Chemical Enhancer Strategy

Ion Pairing for Controlling Drug Delivery

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