Comparative studies on the physical and surface properties of salmeterol xinafoate prepared by spray drying and supercritical fluid processing

With salmeterol xinafoate (SX) as a model compound, this study aims to compare the particles crystallized by Solution Enhanced Dispersion by Supercritical Fluid (SEDS(TM)) process and by spray-drying with those generated by conventional crystallization and micronization.; SX powders were produced in a Buchi-191 spray-drier and in a SEDS(TM) crystallizer under defined conditions.; Spray-drying processing produces either amorphous materials or mixtures of two enantiotropic polymorphic forms, which have been found to be unsuitable for DPI applications after careful characterization studies. In contrast, the two polymorphs (SX-I and SX-II) can be crystallized in pure fine particulate forms separately by the SEDS(TM) technique under different conditions.; In a kinetic study comparing the melt recrystallization rates of SEDS(TM)-processed SX-I, MSX and GSX by DSC, it has quantitatively been shown that polymorphic transformation rate is the slowest for SX-1, reflecting fewer metastable Form II nuclei present in SX-I. Based on the recrystallization rate constants computed from the Avrami-Erofe'ev equation for all the SX Form I samples and using SEDS(TM)-processed SX-I as a 100% Form I reference, the levels of polymorphic impurity (Form II nuclei) in GSX and MSX determined are 0.16% and 0.61% w/w respectively.; The aerosol performance of SX-I is superior to that of MSX. Fine particle fractions of SX-I are higher than that of MSX, suggesting that SX-I of lower surface energy requires lower deaggregation strength to disperse.; Two polymorphs of salmeterol xinafoate (SX-I and SX-II) of high chemical and phase purity and distinct bulk and surface properties have been produced separately under defined conditions in a single step operation by SEDS(TM) processing. The SEDS(TM)-processed SX-I material is superior to the commercial MSX sample in terms of polymorphic purity, fine particle fraction and dispersibility. Compared with spray drying, SEDS(TM) processing, with pressure as an additional operating variable, is a more promising and versatile technique for controlled production of pure crystalline polymorphs, which is normally not achievable with conventional batch crystallization methods. (Abstract shortened by UMI.)...