Solubility Data as a Response for a Challenge for Formulation Chemists: Imidazolium-Based Ionic Liquids and Antitubercular Antibiotic Medicines

Abstract

The evolution of technology is directed to reduce industrial waste from chemical processes to zero. In the past decade interest in ionic liquids (ILs) has grown, and they have been recognized as potential substitutes for volatile organic solvents used in certain chemical processes, including those in the pharmaceutical industry. Following this increasing interest and because ILs can have a great potential for the pharmaceutical industry, we tested the solubility of two antitubercular medicines, pyrazinecarboxamide and isoniazid, in imidazolium ionic liquids, namely [C4mim]­[BF4], [C4mim]­[PF6], [C4mim]­[OTf], and [C8mim]­[OTf], in the range of 279.98 to 417.05 K. Both drugs exhibited an improved solubility in [C4mim]­[BF4] than in the other studied ILs. The solutes had an enhanced solubility in more hydrophilic ILs, such as [C4mim]­[BF4] and [C4mim]­[PF6]. The solubility decreased in ILs containing the hydrophobic anion trifluoromethanesulfonate and with the increasing alkyl chain length in the cation. The solid–liquid phase equilibria of all investigated systems were described using six different correlation equations. The satisfactory results which revealed a good description with an acceptable standard deviation temperature range were collected for isoniazid or pyrazinecarboxamide in [C4mim]­[PF6], [C4mim]­[OTf] and [C8mim]­[OTf]. Comparison to solubility in NTf2 and [C10mim]­[OTf] was provided.

How imidazolium‐based ionic liquids solubilize the poorly soluble ibuprofen? A theoretical study

“…For instance, Mizuuchi et al revealed that both anions and cations played an important role in the solvation of drugs, and the influence of cations was greater than that of anions. Bogel‐Łukasik et al also reported that the strong affinity of the cation with isoniazid leading to a higher solubility of isoniazid in the imidazolium‐based ILs. Nevertheless, there is no clear explanation for the interaction of cations with drugs in the solvation process despite their importance so far.…”

“…Experimentally, plenty of efforts have been attempted to understand the relationship between ILs structure and the solvation mechanism of drugs in ILs for developing new ILs . It has been speculated from various experimental observations that hydrogen bond (HB) interactions between anions and drugs is the major reason for the favorable solvation of drugs in imidazolium‐based ILs . For example, Rogers et al indicated that the amphotericin B formed stronger HB interaction with acetate anion resulting in a higher solubility in ILs than that of itraconazole.…”

“…[23][24][25][26][27][28][29][30][31][32] It has been speculated from various experimental observations that hydrogen bond (HB) interactions between anions and drugs is the major reason for the favorable solvation of drugs in imidazolium-based ILs. [24][25][26][27][28][29][30][31] For example, Rogers et al 29 indicated that the amphotericin B formed stronger HB interaction with acetate anion resulting in a higher solubility in ILs than that of itraconazole. Both NMR and IR evidence of Myerson et al 30 further manifested that the solubility as well as the crystallization of acetaminophen could be adjusted by manipulating the HB interactions between acetaminophen and anions.…”

Structural and conformational properties of 1-decyl-3-methylimidazolium tetrafluoroborate under high pressure

“…Ionic liquids (ILs) have attracted extensive attention because of their unique properties, such as non-volatility, non-flammability, ionic conductivity, liquidity over a wide temperature range, and good dissolving properties [1][2][3]. The structures of ILs are flexible and can be designed according to the needs of specific applications, including novel electrolytes for energy applications and solvents for green processing of insoluble biomolecules [4]. And researchers also found facile and rapid methods for the estimation of fundamental physical properties of ionic liquids using a simple linear correlation between the given IL property and the residual volume of the nalkyl substituents [5].…”

“…Intensity ratio of some vibrational modes to BF 4 symmetric stretching (763cm -1 ) of [C 10 MIM][BF4 ] as a function of pressure. F 1 , F 2 , F 3 and F 4 indicate the intensity ratio of Raman peak 659cm -1 , 756cm -1 , 3159cm -1 and 3158cm -1 to 763cm -1 , respectively.…”