title: Enhancement and in vitro evaluation of amifostine permeation through artificial membrane (PAMPA) via ion pairing approach and mechanistic selection of its optimal counter ion.
abstract: This study presents the results of in vitro evaluation of a series of organic counter ions that form ion pairs with amifostine. The selected counter ions have different lipophilicity, shape and flexibility. Intrinsic octanol buffer partition coefficient and binding constant of the ion pairs were calculated using quasi-equilibrium analysis. Permeation through hydrophobic PAMPA membranes of amifostine and its ion pairs with different counter ions was studied. Three counter ions, succinic acid, benzoic acid and phthalic acid demonstrated an increase in the apparent partition coefficient of amifostine in n-octanol. These counter ions were selected for permeability experiments in PAMPA membranes and an increase of the apparent permeability value Papp (cm/s) was also observed as a function of the counter ion concentration. Phthalic acid produced 1.6-fold increase of log PAB while for benzoic acid and succinic acid the values were 1.2 and 0.75-fold respectively. PAMPA permeability of amifostine significantly increased in the presence of phthalic acid (42-fold), benzoic acid (37-fold) and succinic acid (10.5-fold). This study showed that the permeability of amifostine across a lipophilic membrane was enhanced in the presence of counter-ions resulting ion pair formation.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran. Electronic address: nasimsamieid@yahoo.com.
authors.forename: N
authors.initials: N
authors.lastname: Samiei
authors.forename: A
authors.initials: A
authors.lastname: Shafaati
authors.forename: A
authors.initials: A
authors.lastname: Zarghi
authors.forename: H R
authors.initials: HR
authors.lastname: Moghimi
authors.forename: S M
authors.initials: SM
authors.lastname: Foroutan
mesh_terms: D004999:Amifostine / Q000737:chemistry*; D019817:Benzoic Acid / Q000737:chemistry; D002021:Buffers; D007477:Ions / Q000737:chemistry*; D008567:Membranes, Artificial; D010539:Permeability; D010795:Phthalic Acids / Q000737:chemistry; D019802:Succinic Acid / Q000737:chemistry
chemical_list: D002021:Buffers; D007477:Ions; D008567:Membranes, Artificial; D010795:Phthalic Acids; C032279:phthalic acid; D019817:Benzoic Acid; D019802:Succinic Acid; D004999:Amifostine
keywords: Absorption enhancement; Amifostine; Ion pair; PAMPA; Partition coefficient; Permeability