@article { ISI:000368141200024,
	title = {Drug-drug molecular salt hydrate of an anticancer drug gefitinib and a loop diuretic drug furosemide: an alternative for multidrug treatment},
	journal = {Journal of Pharmaceutical Sciences},
	volume = {104},
	number = {12},
	year = {2015},
	month = {DEC},
	pages = {4207-4216},
	publisher = {WILEY-BLACKWELL},
	address = {111 RIVER ST, HOBOKEN 07030-5774, NJ USA},
	abstract = {<p>A 1:1 monohydrate salt containing gefitinib, an orally administrated chemotherapy treatment for lung and breast cancers and furosemide, a loop diuretic drug, commonly used in the treatment of hypertension and edema, has been prepared. The molecular salt crystallized in triclinic P-1 space group. The CO bond lengths (similar to 1.26 angstrom) in the COOH group show that proton transfer has occurred from furosemide to morpholine moiety of the gefitinib suggesting cocrystal to be ionic. The morpholine moiety of the gefitinib showed significant conformational change because of its involvement in conformation dictating the strong N-H center dot center dot center dot O hydrogen bonding interaction. The strong hydrogen bonding interaction between gefitinib and furosemide places their benzene rings in stacking mode to facilitate the generation of pi-stack dimers. The neighboring dimers are bridged to each other via water molecule through N-H center dot center dot center dot O, C-H center dot center dot center dot O, O-H center dot center dot center dot N, and O-H center dot center dot center dot O interactions. The remarkable stability of the salt hydrate could be attributed to the strong hydrogen bonding interactions in the crystal structure. Interestingly, release of water from the lattice at 140 degrees C produced new anhydrous salt that has better solubility and dissolution rate than salt hydrate. The drug-drug molecular salt may have some bearing on the treatment of patient suffering from anticancer and hypertension. (C) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association</p>},
	keywords = {cancer chemotherapy, cocrystals, crystal engineering, crystal structure, dissolution rate, hydrate, phase transition, solubility, stability, thermal analysis},
	issn = {0022-3549},
	doi = {10.1002/jps.24651},
	author = {Thorat, Shridhar H. and Sahu, Sanjay Kumar and Patwadkar, Manjusha V. and Badiger, Manohar V. and Gonnade, Rajesh G.}
}
@article {48932,
	title = {Novel molecular adducts of an anti-cancer drug vandetanib with enhanced solubility},
	journal = {Crystengcomm},
	volume = {26},
	year = {2024},
	month = {JAN },
	pages = {248-260},
	type = {Journal Article},
	abstract = {<p>The solubility, permeability, and dissolution rate of an active pharmaceutical ingredient (API) are critical factors in determining its pharmacokinetic performance in oral dosage forms. Modifying these properties can potentially enhance the drug{\textquoteright}s pharmacokinetics. Vandetanib (VDTB), classified as a class II anti-cancer drug in the biopharmaceutical classification system (BCS), suffers from low solubility (0.008 mg mL-1) and an extended pharmacokinetic half-life (19 days), necessitating the administration of high doses, which leads to undesirable side effects. To address this issue, we have employed a crystal engineering approach to enhance the solubility of VDTB. We employed the liquid-assisted grinding (LAG) method followed by the slow evaporation technique to prepare novel solid forms of VDTB by incorporating various aliphatic dicarboxylic acids, including succinic acid (SUA), adipic acid (ADA), pimelic acid (PIA), azelaic acid (AZA), and sebacic acid (SBA). These newly obtained solid forms were characterized by SC-XRD, PXRD, TGA, and DSC experiments. The crystal structure analyses revealed a proton transfer between the carboxylic acid group of aliphatic acids and the N-methyl piperidine moiety of VDTB, confirming salt/adduct formation. Additionally, all of the molecular salts were stabilized by charge-assisted N+-HMIDLINE HORIZONTAL ELLIPSISO- hydrogen bonds, while the parent VDTB crystal structure is stabilised by N-HMIDLINE HORIZONTAL ELLIPSISN interactions. Moreover, the solubility and dissolution rate of these new solid forms were assessed in a pH 7.4 phosphate buffer medium, with the results indicating that all of the solid forms, except for VDTB:SBA, exhibited higher solubility compared to pure VDTB. These findings offer promising prospects for the development of an improved VDTB formulation with enhanced pharmacokinetic properties. Successful attempt to improve the solubility and dissolution rate of Vandetanib - an anti-cancer drug, by crystal engineering approach.</p>
},
	keywords = {Amorfization, hydrate, Parameters, Salt, Thyroid-Cancer},
	doi = {10.1039/d3ce01130e},
	author = {Bandaru, Ravi Kumar and Giri, Lopamudra and Krishna, Gamidi Rama and Dandela, Rambabu}
}
