Structural insight into cocrystallization with zwitterionic co-formers: cocrystals of S-naproxen

Abstract

The screening of S-naproxen, S-oxiracetam, S-diprophylline, and levetiracetam with a series of essential and nonessential amino acid co-formers has yielded cocrystals only for S-naproxen, thus showing that amino acids seem to have a preference for forming cocrystals with compounds containing a carboxyl group. Herein, we report the crystal structures of four S-naproxen cocrystals: S-naproxen/L-alanine, S-naproxen/D-alanine, S-naproxen/D-tyrosine, and S-naproxen/D-tryptophan monohydrate. All of the described cocrystals show similar structural motifs, i.e., amino acids form head-to-tail chains with strong charge-assisted hydrogen bonding, which are similar to those found in the individual amino acids, with S-naproxen molecules grafted on them. According to the systematic search of the Cambridge Structural Database for other cocrystals that involve zwitterionic co-formers, charge-assisted hydrogen bonds between amino acid molecules play an essential role, being present in the majority of structures. The results of this work provide an insight into structural aspects of cocrystallization with zwitterionic co-formers, offer new possibilities for S-naproxen pharmaceutical formulations, and can serve as guidelines when developing new cocrystals involving zwitterionic co-formers.

Structure and physicochemical characterization of a naproxen–picolinamide cocrystal

“…To date, 16 cocrystals of NPX have been synthesized and characterized using a variety of techniques, including X-ray diffraction (XRD), infrared (IR) spectroscopy and differential scanning calorimetry (DSC). Cocrystals with ISSN 2053ISSN -2296 the following coformers have been reported: nicotinamide (NA), isonicotinamide (INA), picolinamide (PA) (Neurohr et al, 2015;Castro et al, 2011), trans-1,2-bis(pyridin-4-yl)ethylene (TBPE) (Weyna et al, 2009), duloxetine (Buschmann et al, 2009), tramadol (Buschmann et al, 2010), bipyridine (BPY) and piperazine (PPZ) (Manoj et al, 2014), and several chiral amino acids, including alanine (AL), zwitterionic prolinium (PR), tyrosine (TY), tryptophan (TP) and Noctylglucamine (O-GL) (Tumanova et al, 2014;Tilborg et al, 2013;Yuan et al, 2001). The structures of many of these cocrystals have been determined using single-crystal diffraction (see footnote in Table 1).…”

Salts of Tryptophan with p-Toluenesulphonic Acid and Camphorsulphonic Acids

“…3). The head to tail motif is also present in the structures of DLtryptophan [26,27] (CSD refcodes QQQBTP01, QQQBTP02) and L-tryptophan [25] ( (Fig. 6b).…”

“…Recent reviews have also summarised the structures involving amino acids [14][15][16]. A search of the Cambridge Structural Database [17] gave twelve results when the zwitterionic form of tryptophan was entered as the search query; nine of the structures involve L-tryptophan [13,[18][19][20][21][22][23][24] one structure comprised of D-tryptophan with naproxen [25] and the remaining two structures are pure DL-tryptophan [26,27]. When the cationic form of tryptophan (tryptophanium) is entered as the search query an additional fourteen results are shown [26,[28][29][30][31][32][33][34][35][36][37][38] In this study we have employed R-camphor-10-sulphonic acid and S-camphor-10-sulphonic acid, as S-camphor-10-sulphonic acid has for example been used to resolve DL-phenylglycine [39].…”

Influence of isomerism on recrystallization and cocrystallization induced by CO2 as an antisolvent

“…Changing the API concentration was not an option since 17 mg/mL is close to 5-ASA solubility in the solvent mixture. 56 Cocrystals from zwitterionic species have been fabricated, as for instance with amino acids 56,57 , and even in a cocrystal, the zwitterionic form can be retained. 5).…”