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New multi-component solid forms of anti-cancer drug Erlotinib: role of auxiliary interactions in determining a preferred conformation

Sanphui, Palash and Rajput, Lalit and Gopi, Shanmukha Prasad and Desiraju, Gautam R (2016) New multi-component solid forms of anti-cancer drug Erlotinib: role of auxiliary interactions in determining a preferred conformation. In: ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS, 72 (3). pp. 291-300.

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Official URL: http://dx.doi.org/10.1107/S2052520616003607


Erlotinib is a BCS (biopharmaceutical classification system) class II drug used for the treatment of non-small cell lung cancer. There is an urgent need to obtain new solid forms of higher solubility to improve the bioavailability of the API (active pharmaceutical ingredient). In this context, cocrystals with urea, succinic acid, and glutaric acid and salts with maleic acid, adipic acid, and saccharin were prepared via wet granulation and solution crystallizations. Crystal structures of the free base (Z' = 2), cocrystals of erlotinib-urea (1: 1), erlotinib-succinic acid monohydrate (1: 1: 1), erlotinib-glutaric acid monohydrate (1: 1: 1) and salts of erlotinib-adipic acid adipate (1: 0.5: 0.5) are determined and their hydrogen-bonding patterns are analyzed. Self recognition via the (amine) N-H center dot center dot center dot N (pyridine) hydrogen bond between the API molecules is replaced by several heterosynthons such as acid-pyridine, amide-pyridine and carboxylate-pyridinium in the new binary systems. Auxiliary interactions play an important role in determining the conformation of the API in the crystal. FT-IR spectroscopy is used to distinguish between the salts and cocrystals in the new multi-component systems. The new solid forms are characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) to confirm their unique phase identity.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the INT UNION CRYSTALLOGRAPHY, 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
Keywords: crystal engineering; supramolecular synthon; cocrystals; salts
Department/Centre: Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Depositing User: Id for Latest eprints
Date Deposited: 08 Jul 2016 04:46
Last Modified: 08 Jul 2016 04:46
URI: http://eprints.iisc.ac.in/id/eprint/54136

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