title: New multi-component solid forms of anti-cancer drug Erlotinib: role of auxiliary interactions in determining a preferred conformation.
abstract: 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...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.
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, C. V. Raman Avenue, Bangalore, Karnatakla 560012, India.
authors.forename: Palash
authors.initials: P
authors.lastname: Sanphui
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, C. V. Raman Avenue, Bangalore, Karnatakla 560012, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Rajput
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, C. V. Raman Avenue, Bangalore, Karnatakla 560012, India.
authors.forename: Shanmukha Prasad
authors.initials: SP
authors.lastname: Gopi
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, C. V. Raman Avenue, Bangalore, Karnatakla 560012, India.
authors.forename: Gautam R
authors.initials: GR
authors.lastname: Desiraju
mesh_terms: D000272:Adipates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D000069347:Erlotinib Hydrochloride / Q000737:chemistry*; D005977:Glutarates / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D012492:Salts / Q000737:chemistry; D012995:Solubility; D019802:Succinic Acid / Q000737:chemistry; D014508:Urea / Q000737:chemistry
chemical_list: D000272:Adipates; D000970:Antineoplastic Agents; D005977:Glutarates; D012492:Salts; C029900:adipic acid; D014508:Urea; D019802:Succinic Acid; D000069347:Erlotinib Hydrochloride; C035736:glutaric acid
keywords: cocrystals; crystal engineering; salts; supramolecular synthon