Application of Powder X-Ray Diffraction for Monitoring the Crystallization Process and the Crystal Structure Determination of Enantiomeric Pharmaceutical Drug R(-)-Albuterol Sulfate

CUFFINI SILVIA; PALACIO MARCELA; PALACIOS SARA; PAGOLA SILVINA; STEPHENS P.

Nova Friburgo, Rio de Janeiro, Brasil

Otro; VIII Seminario Latinoamericano de analisis por técnicas de raios X (SARX 2000); 2002

*Racemic albuterol (salbutamol) is composed of an equimolar mixture of stereoisomers. For asthma therapy, R-albuterol is the eutomer and S-albuterol is the distomer. By interacting with b2-adrenoceptors, R-albuterol has bronchodilator, bronchoprotective, anti-edematous properties and inhibits activation of mast cells and eosinophils. S-albuterol does not activate b2-adrenoceptors, so that for many years it was presumed to be biologically inert. Recently, it has been established that regular and excessive use of racemic albuterol induces paradoxical reactions in some subjects with asthma, the pharmacologic profile of S-albuterol has been more carefully defined. Thus, S-albuterol intensifies bronchoconstrictor responses of sensitized guinea pigs and induces hypersensitivity of asthmatic airways. These actions of S-albuterol may explain why racemic albuterol can intensify allergic bronchospasm and promote eosinophil activation in airways (1). Because S-albuterol has detrimental effects in airways, R-albuterol should have advantages over racemic albuterol in the therapy for asthma and it is important to obtain the drug in pure form. The aim of this work is to show how X-ray powder diffraction was used for monitoring the different stages in the crystallization process from racemic compound up to one enantiomer (R). In addition, crystal structure of R-albuterol was solved by High resolution X-ray powder diffraction (HR-XRPD) using Synchrotron Radiation. HR-XRPD data were collected at room temperature at the SUNY X3B1 beamline, N.S.L.S., Brookhaven National Laboratory. The structure solution of R-albuterol was obtained by molecular location using the program PSSP (Powder Structure Solution Program) (2) and the final refinement using FULLPROF and GSAS programs. Crystallografic data of (R)-Albuterol obtained by HR-XRPD structure determination 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. (1) P., Morley J. J. Allergy Clin. Immunol. 1999,104,31-41) (2) Pagola S and Stephens P W, Program PSSP, (Powder Structure Solution Program, available from http://powder.physics.sunysb.edu). Keywords: R-Albuterol, HR-XRPD, PXRD structure determination.