title: Studies on the formation of hydrophobic ion-pairing complex of alendronate.
abstract: A hydrophobic ion-pairing (HIP) concept considering the high dissociation property of alendronate was used as a strategy to improve the bioavailability of alendronate. Alendronate, which has a negative charge, was ion-paired with organic cations, such as tetraheptylammonium bromide (THAB) or tetrabutylammonium iodide (TBAI), to confer hydrophobicity to alendronate, and increase its intestinal permeability. Solutions containing various concentrations (0.5 to 100 mM) of organic cations were combined with an alendronate solution (5 mM) at molar ratios from 0.1:1 to 20:1 under various pHs (pH 2.2, 6.3 and 10.3). Alendronate exhibited high hydrophobicity when coupled with THAB at a molar ratio of 1:10 in pH 2.2. On the other hand, HIP complexes between alendronate and TBAI showed the maximum hydrophobicity at the same molar ratio at pH 10.3. The zeta potentials of alendronate from the aqueous layer of the HIP complex between alendronate and THAB or TBAI increased gradually with increasing alendronate to THAB molar ratio at pH 2.2 or pH 10.3, respectively. This is the first report of the production of hydrophobic ion-paired alendronate.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 305-764, Korea.
authors.forename: Sung-Kyun
authors.initials: SK
authors.lastname: You
authors.forename: Hae-Hyun
authors.initials: HH
authors.lastname: Kwon
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Sang-Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Cheong-Weon
authors.initials: CW
authors.lastname: Cho
mesh_terms: D019386:Alendronate / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000737:chemistry* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010539:Permeability; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*
chemical_list: D050071:Bone Density Conservation Agents; D009943:Organophosphorus Compounds; D000644:Quaternary Ammonium Compounds; C055292:tetrahexylammonium; C050172:tetrabutylphosphonium; D019386:Alendronate