Crystal engineering comprises rational design and modified fabrication of crystal structures offers diverse prospects to selectively enhance the physicochemical properties of drugs via cocrystallization processes. The present study is focused on the preparation, characterization and evaluation of imatinib co-crystals with conformers nicotinamide (ND) and glutamic acid (GA) using crystal engineering approach and their biological evaluation was done in breast adenocarcinoma (MCF7) and Colon Cancer (COLO205) cell lines. Characterization of the prepared co-crystal was done by using analytical tools such as differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermographs of IMND and IMGA cocrystals showed single sharp melting endotherm at 208°C and 149°C respectively, which were in between the melting of drug and both coformer. FT-IR study indicated anime–carbonyl interaction between the participating molecules and appearance of new peaks in PXRD pattern confirms the formation of new co-crystal. Crystal structure of both cocrystals was determined using material studio software (Biovia) from PXRD. In-vitro permeation studies of IM and its cocrystals were determined using Franz-type diffusion cells using silicon membrane as well as in caco-2 cell line also which showed improvement in permeability. Equilibrium solubility and disk intrinsic dissolution rate of cocrystals were found more as compared with pure drug. Pharmacokinetic studies were revealed 3 fold improvement in relative bioavailability than free imatinib. All the results indicate that imatinib cocrystals possess better antitumor efficacy than free drug. Thus cocrystalization approach has been found to be viable technique for improving the solubility, permeability, dissolution and bioavailability of poorly aqueous soluble drug.

Improving solubility, permeability and bioavailability of imatinib using crystal engineering approach with nicotinamide and glutamic acid

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.