Novel co-crystals of the nutraceutical sinapic acid

Abstract

Sinapic acid (SA) is a nutraceutical with known anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-anxiety properties. Novel co-crystals of SA were prepared with co-formers belonging to the category of GRAS [isonicotinic acid (INC), nicotinamide (NIA)], non-GRAS [4-pyridinecarbonitrile (PYC)], and active pharmaceutical ingredients (APIs) [6-propyl-2-thiouracil (PTU)] list of compounds. Structural study based on the X-ray crystal structures revealed the intermolecular hydrogen-bonded interactions and molecular packing. The crystal structure of sinapic acid shows the anticipated acid-acid homodimer along with discrete hydrogen bonds between the acid carbonyl and the phenolic moiety. The robust acid-acid homodimer appears to be very stable and is retained in the structures of two co-crystals (SA[middle dot]NIA and SA[middle dot]PYC). In these cases, co-crystallization occurs via intermolecular phenol O-H[three dots, centered]Naromatic hydrogen bonds between the co-formers. In the SA[middle dot]PTU[middle dot]2MeCN co-crystal the acid-acid homodimer gives way to the anticipated acid-amide heterodimer, with the phenolic moiety of SA hydrogen-bonded to acetonitrile. Attempts at obtaining the desolvated co-crystal led to lattice breakdown, thus highlighting the importance of acetonitrile in the formation of the co-crystal. Among the co-crystals examined, SA[middle dot]INC (5 weeks), SA[middle dot]NIA (8 weeks) and SA[middle dot]PYC (5 weeks) were found to be stable under accelerated humidity conditions (40 [degree]C, 75% RH), whereas SA[middle dot]PTU[middle dot]2MeCN decomposed after one week into individual components due to solvent loss

Solubility of sinapic acid in various (Carbitol + water) systems: computational modeling and solution thermodynamics

“…None of the formulation-based approaches have been reported for solubilization of SA. However, cocrystal technology has been reported for the stability enhancement of SA [25]. Various nutraceuticals/bioactive compounds already established have weak solubilization power in an aqueous media such as water [2].…”

First-line antituberculosis drug, pyrazinamide, its pharmaceutically relevant cocrystals and a salt

“…The major advantage of cocrystallization compared with other solid-state techniques is that no ionisable groups are required either for the drug or for the coformer. Therefore, a large number of neutral coformers including US-FDA approved GRAS (generally regarded as safe) (Burdock & Carabin, 2004), EAFUS (everything added to food in the United States) molecules, nutraceuticals and flavonoids can be used to prepare cocrystals Sinha, Rao Khandavilli et al, 2015;Bethune et al, 2011;Schultheiss et al, 2010Bevill et al, 2014;Brittain, 2012;Madusanka et al, 2014). This is the reason why pharmaceutical cocrystals have been widely explored in the recent past for a large number of neutral drug molecules (Childs & Zaworotko, 2009;Cherukuvada et al, 2016;Trask, 2007 Pyrazinamide (Pyz) is one of the essential drugs listed by the World Health Organization (Bansal & Purohit, 2013;Lindenberg et al, 2004;Bekker et al, 2016) for the treatment of tuberculosis (Zhang & Mitchison, 2003).…”

Distinguishing Cocrystals from Simple Eutectic Mixtures: Phenolic Acids as Potential Pharmaceutical Coformers

“…Indeed, examples of solid state associates formed by these coformers include many pharmaceutically relevant complexes, such as a carbamazepine-cinnamic acid molecular complex and benzoic acid cocrystals with many various APIs and drug-like compounds such as aromatic amides (isonicotinamide, 4-(1 H -pyrazol-1-ylmethyl)­benzamide), amines (1,2-diaminobenzene, 1,2-diaminobenzene), diazepams (nevirapine), methylxanthines (caffeine, etofylline), and other heterocycles (trimethroprim, flucytosine). The abundant hydroxybenzoic acid subclass contains cocrystals of 4-hydroxybenzoic acid, ,− 2-hydroxybenzoic acid, ,,− 3-hydroxybenzoic acid, − 3,5-dihydroxybenzoic acid, − 2,4-dihydroxybenzoic acid, − 2,5-dihydroxybenzoic acid, − 2,6-dihydroxybenzoic acid, − 3,4-dihydroxybenzoic acid, ,, 4-hydroxy-3-methoxybenzoic acid, − and 3,4,5-trihydroxybenzoic acid. − The hydroxycinnamic acid subclass contains binary mixtures formed by 4-hydroxycinnamic acid, ferulic, caffeic, and sinapic acids. ,− The data set used for the model formulation also contains three hydroxynaphthoic acid (1-hydroxy-2-naphthoic acid, 2-hydroxy-1-naphthoic acid, and 6-hydroxy-2-naphthoic acid) solid dispersions. ,− Although these compounds are not naturally occurring nutraceuticals, they can be assigned ...…”