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

Abstract

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.

Fabrication and Characterization of Fast-Dissolving Films Containing Escitalopram/Quetiapine for the Treatment of Major Depressive Disorder

“…The characteristic spectrum of ESC that was obtained by FTIR exhibited peaks at 2954 (C–H stretching), 2231 (C≡N stretching vibration), and 1221 cm −1 (C–N stretching). This spectrum of ESC is consistent with the ESC FTIR spectrum of [ 51 , 52 ]. The pure QUE spectrum showed distinctive peaks at 3310 (O–H stretching), 2944 (C–H stretching), 1597 (N–H bending), and 1063 cm −1 (C–O stretching).…”

“…ESC is suitable for buccal delivery since it has a low MW (324.39 g/mol), low daily dose (10–20 mg), and high log P (0.79) [ 51 ]. Although, its permeability might be hindered by the buccal epithelium and intercellular lipids extruded by membrane-coating granules which represent the permeability barrier for buccal penetration of compounds [ 63 ].…”

Ion Pairs for Transdermal and Dermal Drug Delivery: A Review

“…These include the potential to provide a steady-state release [ 1 ], the avoidance of first-pass metabolism in the case of transdermal formulations and the localisation of application for topical formulations [ 2 ]. Furthermore, the capacity for rapid cessation in cases of adverse reactions, the avoidance of side effects related to oral administration [ 3 ] and, with particular reference to non-steroidal anti-inflammatory drugs, the avoidance of gastrointestinal and renal problems [ 4 ] all contribute to the advantages of this delivery route.…”

Ion-Pair Compounds of Strychnine for Enhancing Skin Permeability: Influencing the Transdermal Processes In Vitro Based on Molecular Simulation

“…The ion-pair strategy is popularly used to improve skin penetration by influencing the physicochemical properties of drugs, thereby avoiding changing the structure and pharmacological actions of the drugs [8,9]. It was reported that the skin permeability of ionpair compounds was clearly influenced by physicochemical properties [10,11], stability [12], ionization in the viable epidermis [13] and the polar surface area [14]. Although the different reasons for the effects of ion-pair compounds on skin permeability were summarized in previous reports, it is still worth further exploring how ion-pair compounds affect the transdermal processes.…”