Application of 1D and 2D solid-state NMR spectroscopy to the characterization of morphine, morphine hydrochloride and their hydrates

GUSTAVO MONTI,; CHATTAH A KARIANA; ROMAÑUK CAROLINA; AYALA ALEJANDRO PEDRO; ALVES DE SANTANA MS; OLIVERA MARIA EUGENIA*; MANZO RUBEN HILARIO; GARRO LINCK YAMILA; AYALA ALEJANDRO PEDRO; GUSTAVO MONTI,; ALVES DE SANTANA MS; CHATTAH A KARIANA; OLIVERA MARIA EUGENIA*; ROMAÑUK CAROLINA; MANZO RUBEN HILARIO; GARRO LINCK YAMILA

JOURNAL OF PHARMACEUTICAL SCIENCES

JOHN WILEY & SONS INC

Lugar: New York; Año: 2017 p. 3033 - 3040

0022-3549

The detailed knowledge of the solid forms of a drug is a key element in pharmaceutical development. Morphine, is an opiate alkaloid widely used to treat severe acute and chronic pain. Much of the available information on its solid state dates from several decades ago. In order to obtain updated and reliable information, 1D and 2D solid-state NMR spectroscopy were used and complemented with powder X-ray diffraction, FTIR and RAMAN spectroscopy and thermal analysis. 13C CPMAS 1D spectra produced a complete identification of the related forms of morphine. Remarkably, 1H-13C heteronuclear correlation spectra, together with FTIR results, gave clear evidence that neither morphine nor its hydrate crystallizes as a zwitterion. In addition, the hydrogen bonds in the anhydrate forms have a different nature or strength than in their respective hydrates. The unique information obtained would be useful for the characterization of morphine as a bulk drug, dosage forms and future developments.