Salts and Ionic Liquid of The Antituberculosis Drug S,S-Ethambutol

Abstract

A salt screen of the antituberculosis chiral basic drug Ethambutol with protic acids resulted in the formation of several salts and an ionic liquid. The protic salt/ionic liquid product was characterized by spectroscopic (ATR-IR and ss-NMR), thermal (DSC and TGA), and X-ray diffraction. Similar to the marketed Ethambutol dihydrochloride salt of the drug, all the new salts were found to be hygroscopic. Moisturefree conditions of the desiccator and rotavapor gave nonhygroscopic materials in a few cases. X-ray crystal structures of two new salts were determined and that of the Ethambutol base and Ethambutol dihydrochloride salt were redetermined in this work.

Crystalline Multicomponent Solids: An Alternative for Addressing the Hygroscopicity Issue in Pharmaceutical Materials

“…Several other salt forms (sulfate, dimesylate, ditosylate, dibesylate, and fumarate) have been prepared earlier but mostly were found to be hygroscopic. 43 series of carboxylic/dicarboxylic acids, trichloroacetic, maleic, oxalic, and terephthalic acids. 127 Among them, the oxalic acid salt showed relatively high stability (up to 48 h) toward hydration under humid conditions.…”

“…The analysis of chloride salt anhydrate structures of these drugs performed by them reveals that the Cl – ion also acts as an H-bond acceptor to satisfy the donor–acceptor imbalance to some extent. However, the H-bond donor to acceptor ratio was found at best in the case of salt hydrates, which was argued as the reason for their high propensity to hydrate formation. − Other potential causes considered for hydrate formation include the presence of hydrophilic functional groups exposed toward crystal facets (surface anisotropy) − and an increased number of crystal defect sites induced during processing (milling, mixing, granulation, and compression). ,, …”

Organic Salts of Pharmaceutical Impurity p-Aminophenol

“…Salts and cocrystals are some of the well-known techniques to improve the physicochemical properties of pharmaceutical and bioactive compounds and can be used in the purification of APIs [18][19][20][21][22][23][24][25][26][27]. Larger pKa variations between the components (usually ΔpKa > 3.0) can lead to the formation of salts, and salts often show greater solubilities than the single individual components [6,28,29].…”

Scalable Synthesis and Supramolecular Assembly of trans‐A2B2 Porphyrins with Pendant Carboxylic Functional Groups

“…It is based on understanding of the strength and directionality of non‐covalent intermolecular interactions that operate between molecular building units . Co‐crystals represent another example of supramolecular materials characterizable in the solid state . These are of a particular interest to pharmaceutical chemists in their search after the most potent forms of compounds with therapeutic activity .…”

“…[6] Co-crystals represent another example of supramolecular materials characterizable in the solid state. [7] These are of a particular interest to pharmaceutical chemists in their search after the most potent forms of compounds with therapeutic activity. [8] Macrocyclic moieties such as e. g. porphyrin molecules are considered as versatile building blocks for the construction of porous clathrate-type assemblies.…”