Purpose. To characterize the surface thermodynamic properties of two polymorphic forms (I and II) of salmeterol xinafoate (SX) prepared from supercritical fluids and a commercial micronized SX (form I) sample (MSX). Methods. Inverse gas chromatographic analysis was conducted on the SX samples at 30, 40, 50, and 60degreesC using the following probes at infinite dilution: nonpolar probes (NPs; alkane C5-C9 series); and polar probes (PPs; i.e., dichloromethane, chloroform, acetone, ethyl acetate, diethyl ether, and tetrahydrofuran). Surface thermodynamic parameters of adsorption and Hansen solubility parameters were calculated from the retention times of the probes. Results. The free energies of adsorption (-DeltaG(A)) of the three samples obtained at various temperatures follow this order: SX-II > MSX approximate to SX-I for the NPs; and SX-II > MSX > SX-I for the PPs. For both NPs and PPs, SX-II exhibits a less negative enthalpy of adsorption (DeltaH(A)) and a much less negative entropy of adsorption (DeltaS(A)) than MSX and SX-I, suggesting that the high -DeltaG(A) of SX-II is contributed by a considerably reduced entropy loss. The dispersive component of surface free energy (gamma(s)(D)) is the highest for MSX but the lowest for SX-II at all temperatures studied, whereas the specific component of surface free energy of adsorption (-DeltaG(A)(S)P) is higher for SX-II than for SX-I. That SX-II displays the highest -DeltaG(A) for the NP but the lowest gamma(s)(D) of all the SX samples may be explained by the additional -DeltaG(A) change associated with an increased mobility of the probe molecules on the less stable and more disordered SX-II surface. The acid and base parameters, K-A and K-D, that were derived from DeltaH(A)(S)P reveal significant differences in the relative acid and base properties among the samples. The calculated Hansen solubility parameters (delta(D), delta(P), and delta(H)) indicate that the surface of SX-II is the most polar and most energetic of all the three samples in terms of specific interactions (mostly hydrogen bonding). Conclusions. The metastable SX-II polymorph possesses a higher surface free energy, higher surface entropy, and a more polar surface than the stable SX-I polymorph.
