Multicomponent Crystal of Metformin and Barbital: Design, Crystal Structure Analysis and Characterization

Abstract

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.

Solid-state landscape and biopharmaceutical implications of novel metformin-based salts

“…In the protonated form, the MET + cation enables the building of heterosynthons based on guanidinium moiety. 21,41 Thus, aiming to favor the guanidiniumÁ Á Ácarboxylate and guanidiniumÁ Á Áamide synthon formation, the coformers screening stage yielded in the saccharin, maleic and malonic acids as suitable coformers. These observations corroborate the existing literature since MET salts based on succinate and acesulfame anions have been recently reported.…”

“…Assignments of the MET proton chemical shifts and spectra interpretation were made using MET 1 H NMR spectra available in the literature. 41,53,54 The 1 H NMR spectra of all new MET salts (see Fig. S10–S13, ESI†) exhibited signals, assigned to the organic counter ions, related to CH (olefinic), –CH 2 (methylene), and –C 6 H 4 (aromatic) groups in the MAL − , MLN − and SAC − anions molecules at 6.01 ppm, 2.69 ppm, and 7.62–7.70 ppm, respectively, which were not observed in the MET–HCl 1 H NMR spectrum (Fig.…”

A high‐performance liquid chromatography method for simultaneous quantification of metformin and ferulic acid in solid dosage forms

“…Chemically, MT is a biguanide that has two methyl groups at position 1 (Figure 1) [3]. Metformin is almost always marketed in the hydrochloride form due to its greater stability than its free base form, which is highly hygroscopic [4].…”