title: Gefitinib-cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies.
abstract: BACKGROUND
  Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs).
  
  
  METHODS
  Phase solubility studies of gefitinib with hydroxypropyl betaCD (HPbetaCD) and randomly methylated betaCD (RMbetaCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC).
  
  
  RESULTS
  Gefitinib formed stable complexes with HPbetaCD and RMbetaCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M(-1) for HPbetaCD and RMbetaCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A(N) type of phase-solubility diagrams, whereas gefitinib and HPbetaCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A(P)-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPbetaCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC.
  
  
  CONCLUSIONS
  Gefitinib formed stable inclusion complexes with HPbetaCD and RMbetaCD, and the solubility and dissolution rate of the drug was significantly increased.
authors.affiliation: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Phillip Lee
authors.forename: Sateesh
authors.initials: S
authors.lastname: Sathigari
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Jean Lin
authors.forename: William R
authors.initials: WR
authors.lastname: Ravis
authors.forename: Gurkishan
authors.initials: G
authors.lastname: Chadha
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Parsons
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Rangari
authors.forename: Nydeia
authors.initials: N
authors.lastname: Wright
authors.forename: R Jayachandra
authors.initials: RJ
authors.lastname: Babu
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins; D000077156:Gefitinib; D006863:Hydrogen-Ion Concentration; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D003505:Cyclodextrins; D011799:Quinazolines; D000077156:Gefitinib