Preparation of hydrophobic drugs cyclodextrin complex by lyophilization monophase solution

A novel method was evaluated for preparation of hydrophobic drugs cyclodextrin (CD) complex in this study. To obtain sterilized drug-CD complex lyophilized powder for injection or other purpose, the CD solution in water and the hydrophobic drug in tertiary butyl alcohol (TBA) were mixed in a suitable volume ratio, filtered through 0.22 microm millpores, and subsequently freeze-dried. A high drug concentration was obtained in the co-solvent due to the good solvency of TBA, which is miscible with water in any proportion, for hydrophobic drugs. Moreover, TBA could be removed rapidly and completely by freeze-drying because of its high vapor pressure and high melting point. The chemical stability of some labile active compounds was also improved in TBA-water co-solvent. Based on the data from differential scanning calormetry (DSC) and X-ray diffractometry (XRD), drug was amorphous in freeze-dried complex. The fourier transform infrared spectra indicated drug-CD interaction was present in drug-CD complex. An enhanced dissolution rate was also obtained in drug-CD complex. These results proved drug-CD complex had been formed after this technique. Thus, this report provided a simple, efficient, and economic technique for preparation of hydrophobic drugs CD complex, which may be useful practically in modifying hydrophobic drugs physicochemical properties and improving their absorption and pharmacodynamics.