Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies

Abstract

Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

Permeation of Ionic Liquids through the skin

“…Neste âmbito, a veiculação de fármacos através da pele tem sido uma das alternativas vez mais exploradas, especialmente os sistemas de veiculação tópicos. Estes sistemas têm inúmeras vantagens comparativamente com outros sistemas de veiculação (oral e parenteral) [3] uma vez que são uma escolha menos dolorosa e não invasiva, onde a aplicação é mais facilitada e conveniente, o que permite uma maior aceitação e adesão à terapêutica por parte do paciente. Este sistema de veiculação permite ainda evitar o efeito de primeira passagem e as variações de pH gástrico, o que lhe confere uma vantagem adicional comparativamente com outras vias de administração, nomeadamente a via oral [4,5]however do not greatly improve the permeation of drugs with molecular weights >500 Da.…”

“…Outra problemática com que a área farmacêutica se depara, consiste na baixa solubilidade, de muitos dos fármacos, em água e nos solventes orgânicos que se podem utilizar. Assim, uma das formas de ultrapassar este obstáculo é a de desenvolver excipientes funcionais que to synthesize ILs with specific physical and chemical properties [3,7]. Currently, there are several studies that involve the incorporation of ILs into topical formulations, demonstrating that there is an impact of these salts on the solubility and permeation of poorly soluble active compounds [3,[12][13][14][15][16].…”

“…In this context, the delivery of drugs through the skin has been one of the increasingly explored alternatives, especially topical delivery systems. These systems have numerous advantages compared to other delivery systems (oral and parenteral) [3] as it is a less painful and non-invasive choice, with more facilitated and convenient application, which allows for greater acceptance and adherence to therapy by the patient. This delivery system also allows the avoidance of the first pass effect and variations in gastric pH, which gives it an additional advantage compared to other routes of administration, particularly the oral route [4,5].…”

“…Assim, uma das formas de ultrapassar este obstáculo é a de desenvolver excipientes funcionais que to synthesize ILs with specific physical and chemical properties [3,7]. Currently, there are several studies that involve the incorporation of ILs into topical formulations, demonstrating that there is an impact of these salts on the solubility and permeation of poorly soluble active compounds [3,[12][13][14][15][16]. However, there are few studies evaluating the functionality of these salts in non-cytotoxic percentages [3,16], and to the best of our knowledge none consider to what extent these ionic liquids permeate the skin, which is relevant information when dealing with topical delivery systems.…”

“…Thus, one of the ways to overcome this complication is to develop functional excipients that may increase the solubility and incorporation of these poorly soluble drugs into developed delivery systems. In this context, ionic liquids (ILs) have been studied as promoters of solubility and permeation and some studies have shown the use of these materials for this purpose [3,7,8,14,15]. Ionic liquids are organic salts [7,8], constituted by ions, an organic cation and an organic or inorganic anion [7,9], which are liquid at temperatures below 100 ºC [10,11] or, in some cases, liquids at room temperature [3,9].…”