Choline-Amino Acid Ionic Liquids as Green Functional Excipients to Enhance Drug Solubility.

Rita Caparica,Ana Júlio,Maria Araújo,André Baby,Ana Fernandes,João Costa,Tânia Santos De Almeida

doi:10.3390/pharmaceutics10040288

Abstract

The development of effective forms to incorporate poorly soluble drugs into delivery systems remains a problem. Thus, it is important to find alternatives such as finding excipients that increase drug solubility. Ionic liquids (ILs), particularly choline-based ILs, have been studied as solubility enhancers in drug delivery systems. Nonetheless, to acknowledge this property as a functionality, it needs to be proven at non-toxic concentrations. Hence, herein two choline-amino acid ILs were studied as functional excipients by evaluating their influence on the solubility of the poorly water-soluble ferulic acid and rutin, while considering their safety. The solubility of the drugs was always higher in the presence of the ILs than in water. Ionic liquids did not affect the radical scavenging activity of the drugs or the cell viability. Moreover, stable oil-in-water (O/W) emulsions were prepared containing each drug and the ILs, allowing a significantly higher drug loading. Globally, our results suggest that choline-based ILs may act as green functional excipients, since at non-toxic concentrations they considerably improve drug solubility/loading, without influencing the antioxidant activity of the drugs, the cell viability, or the stability of the formulations.

Highlights

Over the last few years, the pharmaceutical and cosmetic industries have been facing several problems in the development of delivery systems, namely the poor solubility, permeability and stability of certain drugs
To understand the influence of the Ionic liquids (ILs) on the solubility of the poorly soluble ferulic acid and rutin, solubility studies were performed in water and in different water:IL mixtures
Even though it is relevant to understand this concentration impact, the main goal of this study was to evaluate if, at non-toxic concentrations [14], the studied ILs significantly enhance the solubility of ferulic acid and rutin, to ensure their safe functionality

Summary

Introduction

Over the last few years, the pharmaceutical and cosmetic industries have been facing several problems in the development of delivery systems, namely the poor solubility, permeability and stability of certain drugs. In the research and development of new chemical entities (NCEs), the low solubility is a growing and emerging problem [1,2,3]. More than 40% of NCEs developed are practically insoluble in water [4]. About 75% of the drugs candidates have low solubility and belong to classes II and IV of the Biopharmaceutical Classification System [1]. Several strategies have been used to overcome this problem, like the encapsulation of actives into nanoparticles [5,6], but there is still much to be done. It is of the utmost importance to find new ways to overcome this challenge, such as finding eco-friendly excipients that may act as functional ingredients at non-toxic concentrations

Objectives

Methods

Results