TY - JOUR
T1 - Influence of polymorphism on the surface energetics of salmeterol xinafoate crystallized from supercritical fluids
AU - Tong, H. H.Y.
AU - Shekunov, B. Y.
AU - York, P.
AU - Chow, A. H.L.
N1 - Funding Information:
Financial support was received from the Research Grant Council of Hong Kong (Earmarked Grant CUHK4244/98M).
PY - 2002
Y1 - 2002
N2 - 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 60°C 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 (-ΔGA) of the three samples obtained at various temperatures follow this order: SX-II > MSX ≅ 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 (ΔHA) and a much less negative entropy of adsorption (ΔSA) than MSX and SX-I, suggesting that the high -ΔGA of SX-II is contributed by a considerably reduced entropy loss. The dispersive component of surface free energy (γsD) 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 (-ΔGASP) is higher for SX-II than for SX-I. That SX-II displays the highest -ΔGA for the NP but the lowest γsD of all the SX samples may be explained by the additional -ΔGA 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, KA and KD, that were derived from ΔHASP reveal significant differences in the relative acid and base properties among the samples. The calculated Hansen solubility parameters (δD, δP, and δH) 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.
AB - 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 60°C 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 (-ΔGA) of the three samples obtained at various temperatures follow this order: SX-II > MSX ≅ 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 (ΔHA) and a much less negative entropy of adsorption (ΔSA) than MSX and SX-I, suggesting that the high -ΔGA of SX-II is contributed by a considerably reduced entropy loss. The dispersive component of surface free energy (γsD) 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 (-ΔGASP) is higher for SX-II than for SX-I. That SX-II displays the highest -ΔGA for the NP but the lowest γsD of all the SX samples may be explained by the additional -ΔGA 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, KA and KD, that were derived from ΔHASP reveal significant differences in the relative acid and base properties among the samples. The calculated Hansen solubility parameters (δD, δP, and δH) 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.
KW - Hansen solubility parameters
KW - Inverse gas chromatography
KW - Salmeterol xinafoate polymorphs
KW - Supercritical fluid crystallization
KW - Surface energetics
UR - http://www.scopus.com/inward/record.url?scp=0036001398&partnerID=8YFLogxK
U2 - 10.1023/A:1015358129817
DO - 10.1023/A:1015358129817
M3 - Article
C2 - 12069167
AN - SCOPUS:0036001398
SN - 0724-8741
VL - 19
SP - 640
EP - 648
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 5
ER -