Solid State characterization by HR-XRPD and NMR spectroscopy of chiral drug: Albuterol Sulfate (racemic and enantiomer compounds)

SILVIA CUFFINI; MARCELA PALACIO; CARLOS.FERRAYOLI; SARA PALACIOS; SILVINA PAGOLA; J.SCHNEIDER; P. W. STEPHENS

Erice, Italy

Otro; Diversity amidst Similarity: A Multidisciplinary Approach to Polymorphs, Solvates and Phase Relationships. 35th International School of Crystallography; 2004

INTERNATIONAL SCHOOL OF CRYSTALLOGRAPHY

   Racemic albuterol (salbutamol) is composed of an equimolar mixture of stereoisomers used for asthma therapy (1). R-albuterol  should have advantages over racemic albuterol in this therapy  and it is important to obtain the drug in pure form. The aim of this work is to show the solid state characterization of racemic  and R enantiomer compounds  by  High resolution X-ray powder diffraction  (HR-XRPD) using Synchrotron Radiation and solid state NMR spectroscopy. HR-XRPD data  were collected at room temperature at the SUNY X3B1 beamline, N.S.L.S. (BNL). The crystal structure solution of R-Albuterol was obtained by molecular location using the program PSSP (Powder Structure Solution Program) (2). High-resolution solid-state 13C NMR measurements were carried out in a Varian Unity INOVA spectrometer at 9.4T. Crystallografic data of (R)-Albuterol obtained by HR-XRPD  are , a =  28.0872(18)  b =  6.1464(4)  c =  16.5095(11), Alpha =  90,Beta = 95.558(4),  Gamma =  90,  with monoclinic system and space group C2, presenting two non-equivalent molecule per cell. The 13C NMR lines were assigned using literature information (3) and comparing the CP and non-protonated spectra. Lines from C1, C3/C5, C10 and methyl groups are clearly split, indicating  the presence two non-equivalent molecules. The combination of solid-state NMR spectroscopy and HR-XRPD provide a complete solid characterization of these type of drugs.