Hydroxypropyl-β-cyclodextrin inclusion complexes for transdermal delivery:: Preparation, inclusion properties, stability, and release behavior

Hydroxypropyl-beta-cyclodextrin (HPCD), a highly water-soluble derivative, was synthesized by the substitution of the hydroxyl groups in the glucopyranose units of beta-cyclodextrin (beta-CD) with hydroxypropyl groups to improve its solubility in aqueous solution and its biocompatibility. beta-CD has only limited water solubility (similar to 1.8 g/mL at ambient temperature), whereas HPCD showed high water solubility and also dissolved in solvents such as methanol, ethanol, DMF, and DMSO. To investigate their feasibility for transdermal delivery applications, HPCD inclusion complexes containing several lipophilic guest molecules (retinol, tocopherol, and genistein) were prepared through complex formation by taking advantage of the special molecular structure of HPCD, which has a hydrophobic interior cavity and a hydrophilic exterior. The molar inclusion efficiency of guest molecules within HPCD was ca. 8 similar to 12 % when the feed molar ratio of guest molecules to CD was 1. The inclusion efficiency was influenced by the feed molar ratio and by the type of guest molecule. The stabilities of the inclusion complexes were investigated with respect to the temperature, pH, and solvent. HPCD complexes exhibited enhanced stability in comparison with those of the parent beta-CD. From an in vitro skin permeation study using a Frantz diffusion cells, ca. 70 similar to 90 % permeation of guest molecules was observed within 7 days.