Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool

Abstract

Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p-coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.

Biobased Ionic Liquids as Multitalented Materials in Lipidic Drug Implants

“…It should be noted that to prove the ILs actually have valid functionalities, these materials were incorporated into the formulations at non-toxic concentrations, namely 0.2% ( v / v ) that is known to be the maximum percentage where cell viability is maintained in HaCaT cells (human keratinocytes) from previous studies performed by our group [ 13 , 15 ].…”

“…To evaluate the dye content distribution, the developed lipidic implants were produced in the presence of one lipophilic dye, Sudan III, or one hydrophilic dye, Methylene Blue, purchased from Sigma-Aldrich (St. Louis, MO, USA) and Sigma-Aldrich (Darmstadt, Germany), respectively. The incorporated ILs, namely (2-hydroxyethyl)-trimethylammonium- l -phenylalaninate [Cho][Phe] and (2-hydroxyethyl)-trimethylammonium- l -glutaminate [Cho][Glu] were synthesized and characterized within the context of other studies developed by our group [ 12 , 15 ].…”

“…ILs are poorly coordinated organic salts that have been defined as a liquid below 100 °C or even at room temperature [ 11 , 12 , 13 , 14 , 15 ]. They have high thermal and chemical stability, low vapor pressure, are negligibly volatile, and present good ionic conductivity [ 16 , 17 ].…”

“…They have high thermal and chemical stability, low vapor pressure, are negligibly volatile, and present good ionic conductivity [ 16 , 17 ]. ILs have been used in pharmaceutical research for several applications [ 18 ] such as solubility promotors [ 12 , 13 , 15 , 19 , 20 , 21 , 22 ], as catalysts in the synthesis of active pharmaceutical ingredients [ 19 , 23 , 24 ], as oil or water substitutes [ 24 , 25 , 26 , 27 ], as surfactants in emulsions and micro emulsions [ 12 , 15 , 19 , 20 , 25 , 26 , 27 ], or even integrated with nanomaterials [ 28 , 29 , 30 , 31 ]. Hence, ILs may potentially be key materials to be incorporated in different delivery systems such as lipidic implants to improve their efficiency.…”

“…Hence, ILs may potentially be key materials to be incorporated in different delivery systems such as lipidic implants to improve their efficiency. Specifically in this study, two choline-based ILs were incorporated into lipidic implants at non-toxic concentrations [ 13 , 15 ] and the impact of these materials on the formulation procedure and in the performance of the developed systems was evaluated. The lipidic implants were produced in the presence and absence of ILs with variable compositions and with or without the studied drugs, namely caffeine and poorly water-soluble salicylic acid and rutin.…”