Novel pharmaceutical co-crystals of gefitinib: synthesis, dissolution, cytotoxicity, and theoretical studies

被引：5

作者：

Shaik, Althaf ^{[1
]}

Bhagwat, Pranav Umesh ^{[1
]}

Palanisamy, Parimaladevi ^{[2
]}

Chhabria, Dimple ^{[1
]}

Dubey, Pankaj ^{[1
]}

Kirubakaran, Sivapriya ^{[1
]}

Thiruvenkatam, Vijay ^{[2
]}

机构：

[1] Indian Inst Technol Gandhinagar, Discipline Chem, Gandhinagar 382355, Gujarat, India

[2] Indian Inst Technol Gandhinagar, Discipline Biol Engn, Gandhinagar 382355, Gujarat, India

来源：

CRYSTENGCOMM | 2023年 / 25卷 / 17期

关键词：

ANTICANCER DRUG GEFITINIB; COCRYSTALS; FORMULATION; FUROSEMIDE; ACID;

D O I：

10.1039/d3ce00056g

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Gefitinib (GEF) is an ATP-competitive inhibitor used in the treatment of advanced non-small cell lung cancer. However, the pharmaceutical efficacy of this drug is currently limited due to poor aqueous solubility (2.55 mu g mL(-1)). Therefore, we engineered three co-crystals of GEF with suitable coformers like cinnamic acid (CA), sorbic acid (SA) and resorcinol (RES). Solvent assisted grinding combined with slow evaporation of solvent resulted in three co-crystals. Structural elucidation of the crystals revealed that GEF formed a 1 : 1 co-crystal with CA (GCA), while it formed a 1 : 1 : 1 co-crystal hydrate with RES (GRES center dot H2O) and SA (GSA center dot H2O). Further, dissolution studies showed that there is an increase in the solubility of the cocrystal GCA. The synthesized co-crystals showed a comparable potency with respect to GEF in a cell viability assay. In addition, we quantified various intermolecular interactions in the co-crystals of GEF using Hirshfeld surface and 2D fingerprint plot analysis. The improvement in solubility along with the comparable efficacy of co-crystals cement the importance of pharmaceutical cocrystals in improving the physicochemical properties of drug molecules.

引用

页码：2570 / 2581

页数：12

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