The utility of cyclodextrins for enhancing oral bioavailability.

Cyclodextrins (CD) have been utilized extensively in pharmaceutical formulations to enhance oral bioavailability. A critical review of the literature in which cyclodextrins were utilized for this purpose was conducted. The goal of this review was to determine if quantitative guidelines for drug and cyclodextrin properties necessary for bioavailability enhancement using cyclodextrins could be extracted. Twenty-eight studies were examined in which the focus was on the use of cyclodextrins as solubilizers to enhance bioavailability. Commonly observed factors included: utilization of pre-formed complex rather than physical mixtures, drug hydrophobicity (logP > 2.5), low drug solubility (typically< 1 mg/ml), moderate binding constant (< 5000 M(-1)), low dose (< 100 mg), and low CD:drug ratio (< 2:1). These general guidelines, however, did not apply to all studies. Quantitative guidelines useful to a formulation scientist considering the use of cyclodextrins were difficult to develop due to missing information and the complicated manner in which drug and cyclodextrin properties interact to influence key drug delivery processes (e.g., dissolution, absorption). The mechanisms by which cyclodextrins influence these processes, again emphasizing solubilization capabilities, are discussed to provide further insight into why cyclodextrins will increase bioavailability in certain cases but not influence or possibly decrease bioavailability in others.