Rapamycin-cyclodextrin complexation: improved solubility and dissolution rate

The objective of this study was to improve poor aqueous solubility and dissolution properties of anticancer drug rapamycin through formation of inclusion complexes with natural and modified cyclodextrins. Of the cyclodextrins tested, γ-cyclodextrin and hydroxypropyl-γ-cyclodextrin did not complex with rapamycin. However, complexes of rapamycin with β-cyclodextrin, methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin were prepared and characterized by techniques such as Fourier Transform infrared spectroscopy, differential scanning calorimetry, phase solubility analysis and in vitro dissolution studies. According to the characterization data for the complexes, rapamycin water solubility was highly enhanced by all three β-cyclodextrins with methyl-β-cyclodextrin complex resulting in particularly higher solubility enhancement. FTIR spectra and DSC thermograms supported the formation of inclusion complexes. The complexes showed highly improved dissolution rate in water. Complexation with cyclodextrin derivatives such as methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin can provide promising alternatives for the formulation of rapamycin.