Multicomponent crystals of erlotinib

Area of Science:

• Crystallography
• Materials Science
• Pharmaceutical Chemistry

Background:

• Erlotinib is a small-molecule inhibitor of the epidermal growth factor receptor (EGFR).
• It is a key therapeutic agent for non-small-cell lung cancer (NSCLC).
• Understanding the solid-state forms of erlotinib is crucial for drug formulation and stability.

Purpose of the Study:

• To elucidate the crystal structures of erlotinib monohydrate, erlotinib hemioxalate salt, and a novel erlotinib-fumaric acid cocrystal.
• To investigate the role of intermolecular interactions, such as hydrogen bonding and pi-pi stacking, in the assembly of these crystalline forms.
• To characterize the hydrogen-bonded networks formed in the crystal packing of these erlotinib multicomponent crystals.

Main Methods:

• Single-crystal X-ray diffraction was used to determine the crystal structures.
• Analysis of intermolecular interactions, including hydrogen bonds and aromatic pi-pi stacking, was performed.
• Characterization of hydrogen-bonded networks within the crystal lattices was conducted.

Main Results:

• The crystal structures of erlotinib monohydrate (I), erlotinib hemioxalate salt (II), and erlotinib fumaric acid hemisolvate dihydrate (III) were determined.
• Water molecules in (I) and (III) form tetrameric and hexameric hydrogen-bonded networks.
• In (II), cations and anions form a tetrameric hydrogen-bonded network, with oxalate and fumarate anions located across inversion centers.

Conclusions:

• The study successfully elucidated the crystal structures of three distinct erlotinib multicomponent forms.
• Intermolecular interactions, particularly hydrogen bonding, play a significant role in dictating the crystal packing and network formation.
• These findings provide valuable insights into the solid-state chemistry of erlotinib, relevant for pharmaceutical development.