Polymorphism is the ability of a solid molecule to change its crystalline structure. Thus, crystal engineering has been a continually growing focus within the pharmaceutical industry since polymorphic forms of a drug can greatly impact its solubility and stability. Polymer-induced heteronucleation (PIH) by surface modification of nanoparticles is an alternative approach to designing pharmaceutical crystals. Because diffraction methods are of limited use to characterize crystals prepared by PIH, it is necessary to employ high-resolution solid-state NMR (SS-NMR). Here conformational polymorphism is explored in the pharmaceutical Erlotinib. Erlotinib is a tyrosine kinase inhibiting drug used in the treatment of pancreatic and non-small cell lung cancers. The transmembrane tyrosine kinase epidermal growth factor receptor (EGFR), which is responsible for causing a signal cascade triggering cell proliferation, is highly expressed in these forms of cancers. Erlotinib serves to block ATP from binding to EGFR and therefore prevent the signal cascade. A new polymorphic form of Erlotinib has been prepared by PIH using self-assembled monolayers of zinc or nickel oxide tiles in organic acid. Conformational changes of the polymorphs are evident in the chemical shift changes of the 13C cross-polarization and magic angle spinning spectra. Spectral editing using a dipolar dephasing pulse sequence was performed to help assign the 13C spectra. Inversion recovery with carbon detection demonstrate differences in proton spin-lattice relaxation of the forms. Natural abundance 15N spectra were acquired to help understand the ethynylphenyl ring orientation with respect to the quinazoline ring moiety.

Characterization of erlotinib polymorphs by solid-state NMR

2019 Spring National Meeting

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