Quetiapine free base complexed with cyclodextrins to improve solubility for parenteral use

Quetiapine, an antipsychotic drug used for schizophrenia treatment, is poorly water soluble, and therefore, administration of the more water-soluble quetiapine fumarate is preferred. Absorption of quetiapine through biological membranes may be improved by enhancing the solubility of the quetiapine base, the non-ionic form. In this study, the currently used salt form was converted into the free base (oily material). We employed cyclodextrins (CDs) as pharmaceutical additives to improve the solubility of the quetiapine base. The formation of quetiapine-β-cyclodextrin (β-CD) complexes was studied by phase solubility studies, continuous variation method, NMR spectroscopy, and powder X-ray diffraction. The formation of a poorly water-soluble complex was confirmed by the phase solubility study, and the interaction between quetiapine and β-CD in water was confirmed by NMR spectroscopy. In addition, the effects of β-CD derivatives (glucosyl-β-CD, maltosyl-β-CD, 2-hydroxypropyl-β-CD, dimethyl-β-CD, and trimethyl-β-CD) on the solubility of the quetiapine base were studied. The findings indicated that the aforementioned hydrophilic β-CD derivatives could be used as pharmaceutical additives of quetiapine for parenteral formulations as a result of the improved solubility of the quetiapine base because of inclusion complexation. Therefore, converting the currently used salt form into the free base, investigating the free base as a candidate for CD inclusion, and converting the oily material such as the free base into a powder by forming an inclusion complex that is easy to deal with is considered a worthwhile approach that may lead to novel formulations of the drug in question.