Linearity was characteristic of the AL-type system (19) and suggested that water-soluble complexes formed in the solution.
Furthermore, the slope value (0.0011) was lower than 1.0, thus indicating that inclusion complexes in a molar ratio of 1:1
formed between the guest (LVS) and host (HPβ-CD) molecules. The stability constant (Kc) for the complexes at 37 °C (assuming
a 1:1 stoichiometry) calculated from the slope of the initial straight portion of the solubility diagram was 917.67 M–1 , which indicated a suitable and stable complex formation. It is reported that cyclodextrin-drug complexes with Kc values
in the range of 200–5000 M–1 show improved dissolution properties and, hence, better bioavailabilities (19).
The values of Gibbs free energy change (ΔGtr°) were calculated to understand transfer process of LVS from pure water to aqueous solution of HPβ-CD. The ΔGtr° values of LVS from pure water to aqueous solutions with various concentrations of HPβ-CD at 37 °C were calculated using
the following equation (25):
|
in which So/Ss is the ratio of molar solubility of LVS in an aqueous solution of HPβ-CD to that of the pure water. The obtained values of
Gibbs free energy are shown in Table II. The ΔGtr° values provide information about whether the reaction condition is favorable or unfavorable for drug solubilization in the
aqueous carrier solution. Negative Gibbs free energy values indicate favorable conditions. The ΔGtr° values were all negative for HPβ-CD at various concentrations, thus indicating the spontaneous nature of LVS solubilization.
These values decreased with increased concentration of HPβ-CD, thereby demonstrating that the reaction became more favorable
as the concentration of HPβ-CD increased.
Drug content. The drug content (%w/w) of the complexes prepared by the coevaporation and the kneading methods and the physical mixture were
found to be 21.02 (±0.23)%, 20.78 (±0.39)%, and 14.74 (±5.35)%, respectively, which corresponds approximately with the stoichiometric
ratio of the complex and indicates chemical stability and content uniformity of LVS in its complex form. The content uniformity
for the physical mixture is lower than the complexes prepared by the coevaporation and the kneading methods. This effect may
be attributed to insufficient mixing caused by simple mixing of powders without applying pressure (HPβ-CD and LVS). The final
moisture content of the pure drug, the physical mixture, and the complex prepared by the coevaporation and the kneading methods
were 0.23%, 0.89%, 1.09%, and 1.14%, respectively.
Characterization of complexes. IR spectroscopic analysis. Fourier transform infrared spectroscopy (FT IR) has been used to assess the interaction between β-CD and guest molecules in
the solid state. Upon complexion, the peak band of the guest shifts in the absorption spectrum. Nonetheless, some of the changes
are very subtle and require careful interpretation of the spectrum (26).
|
