Flavonoids are an important class of natural-organic compounds widely used in the food, medicine and cosmetic industries mainly because of their pharmacological functions and biological activities like antioxidative, anti-inflammatory properties etc. The presence of multiple hydrophobic benzene rings leads to the low solubility of flavonoids in water thus limiting its applications as parentrals, oral preparation etc. Cocrystals on the other hand refers to a crystal structure, product of combining two or more molecules in the same crystal lattice held together by non-covalent bonds in a fixed stoichiometric ratio. A composition of one or more APIs and cocrystal formers (CCF) is specifically referred to as pharmaceutical cocrystals.
Recently, pharmaceutical cocrystal technology is a major research hotspot mainly focusing on insoluble drugs. Most flavonoid molecular structures contain multiple phenolic hydroxyl groups that act as proton acceptors and donors, allowing them to form various intermolecular hydrogen bonds with cocrystal formers (CCFs). The cocrystals of compounds that are discussed in the referenced research paper are as follows flavonoids: luteolin, baicalein and chrysin; isoflavones are genistein and daidzein; dihydro flavonoids are naringenin and hesperetin; flavonols are quercetin, myricetin, fisetin, kaempferol; Dihydrochalcone is phloretin; Flavan-3-alcohols (Flavan-3-OLS) are (−)-catechins, (+)-catechin.
BCSII and BCSIV, which are poorly soluble drug candidates, accounted for almost 90% of the development of innovative drugs. Of the drugs already on the market, poorly soluble drugs accounts for less than 40%. Solubility is an unavoidable issue when solid active ingredients are finally on the market. Poor solubility results in poor absorption. Many candidate drugs had to be discontinued because they could not find a suitable solubilization method. Due to the high cost and tedious acquisition of early drug candidates, the question of how to quickly and efficiently screen solubilization methods using milligram-scale compounds to improve PK and shorten the development cycle is increasing each year. Although flavonoids have a wide range of pharmacological activities, their solubility problems limit their widespread medical application. By using co-crystal technology to introduce new pharmaceutically acceptable co-crystal forming agents such as caffeine, nicotine, and isonicotinamide without altering their structures can effectively improve their chemical and physical properties such as improving solubility, improved bioavailability, etc., further promote the development of insoluble active ingredients in the pharmaceutical field. However, there are certain limitations for example: The solubility of fisetin-isonicotinamide, fisetin-caffeine, and fisetin-nicotinamide is more than twice that of fisetin, but its main anti-tumor properties have not been further studied. However, this is an effective and rapid new route for secondary development of flavonoids and drug development with independent intellectual property rights and will be a topic of interest for future researchers.
Reference:
Xia, Y.F., Xu, R.J. and Jiang, C.J. (2022) The Research Progress on Cocrystals of Flavonoids. Open Access Library Journal, 9, 1-18. doi: 10.4236/oalib.1108320.
By Gauri Pillai
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