title: Quetiapine free base complexed with cyclodextrins to improve solubility for parenteral use.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University; 1–100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464–8650, Japan. noriko30@dpc.agu.ac.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Ogawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kaga
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Endo
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Nagase
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furuishi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Ueda
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000737:chemistry*; D007263:Infusions, Parenteral; D009682:Magnetic Resonance Spectroscopy; D000069348:Quetiapine Fumarate; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D014150:Antipsychotic Agents; D003505:Cyclodextrins; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate