Studies on the formation of hydrophobic ion-pairing complex of alendronate

College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, 305-764, Korea.
Archives of Pharmacal Research (Impact Factor: 2.05). 08/2009; 32(7):1055-60. DOI: 10.1007/s12272-009-1711-2
Source: PubMed


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.

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    • "In particular, F101 and F112 showed a zeta potential of −7.19 ± 0.46 and 1.76 ± 0.28 mV, respectively. e zeta potential changed to a positive value from −6.98 ± 0.64 to 1.36 ± 0.41 mV with increasing chitosan to alendronate weight ratio from 0.05 to 1, suggesting that alendronate and chitosan can be complexed electrostatically during particle preparation (You et al., 2009). e changes in the solid state of alendronate were assessed using DSC analysis of the alendronate microparticles (Figure 2). "
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