The novel application of tertiary butyl alcohol in the preparation of hydrophobic drug-HPbetaCD complex.

摘要

This report describes a novel application of tertiary butyl alcohol (TBA) in the preparation of hydrophobic drug-hydroxypropyl beta-cyclodextrin (HPbetaCD) complex. The straightforward, economic preparation procedure consists of dissolving both the hydrophobic drug and HPbetaCD in TBA, which is subsequently freeze-dried to give the hydrophobic drug-HPbetaCD complex in the form of a porous powder. TBA was selected as the medium due to it being a good solvent for hydrophobic drug and HPbetaCD; in addition, it is also a versatile lyophilization medium and is widely used in pharmaceutical processes. In this study, ketoprofen and nitrendipine were used as model drugs and their HPbetaCD complexes were prepared by lyophilization of the TBA system. Based on the data from differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), the drugs were amorphous in freeze-dried samples. The infra-red (IR) spectrum indicated that a drug-HPbetaCD interaction took place in the freeze-dried complex. Dissolution experiments showed that the hydrophobic drug dissolved rapidly from the HPbetaCD complex in both simulated gastric juice and simulated intestinal fluid. These results confirmed that this technique produced a hydrophobic drug-HPbetaCD complex. TBA was found to be a suitable freeze-drying medium for the preparation of hydrophobic drug-HPbetaCD complex. This approach is versatile, energy-conserving and can easily be scaled up. It is expected to have further application in modifying the physicochemical characteristics of hydrophobic drugs and improving their absorption and pharmacodynamic properties.