title: In vitro and in vivo iontophoretic transdermal delivery of an anti-parkinsonian agent.
abstract: To objective of this work was to study the feasibility of iontophoretic delivery of SLV 318 (7-(4-benzyl-1-piperazinyl)-2(3H)-benzoxazolone methanesulfonate) across hairless rat skin in vitro and in vivo. The effect of counter-ions and temperature were investigated for optimizing SLV 318 solubility. The effect of electrode efficiency and total current applied on the delivery of SLV 318 were studied using Franz diffusion cells and samples were analyzed using HPLC. Delivery increased with increasing concentration. For current-time combinations, electrode had to be replaced every 9h. Passive, iontophoretic (0.1 mA/cm(2) for 1h) and intravenous studies were performed in vivo. Blood samples collected were analyzed using LC-MS/MS. SLV 318 had higher solubility with NaCl (75 mM) as a counter-ion at 25°C than with other counter-ions tested. In vivo iontophoresis significantly enhanced the permeation and also reduced its lag time (P<0.05). The C(max) of SLV 318 during 1h iontophoresis was 6.56 ± 0.68 ng/mL at 1.31 ± 0.29 h (T(max)) as compared to 2.96 ± 0.29 ng/mL at 25.32 ± 0.67 h (T(max)) by 24h passive permeation. The in vitro and in vivo data has shown the feasibility to enhance delivery of SLV 318 by iontophoresis.
authors.affiliation: College of Pharmacy and Health Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
authors.forename: V
authors.initials: V
authors.lastname: Vemulapalli
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Siddoju
authors.forename: R
authors.initials: R
authors.lastname: Conjeevaram
authors.forename: H
authors.initials: H
authors.lastname: Teunissen
authors.forename: T
authors.initials: T
authors.lastname: Myers
authors.forename: A K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001583:Benzoxazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D005240:Feasibility Studies; D006863:Hydrogen-Ion Concentration; D007478:Iontophoresis; D008698:Mesylates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010539:Permeability; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D053719:Tandem Mass Spectrometry; D013696:Temperature
chemical_list: C573965:7-(4-benzyl-1-piperazinyl)-2(3H)-benzoxazolone methanesulfonate; D000978:Antiparkinson Agents; D001583:Benzoxazoles; D002021:Buffers; D008698:Mesylates; D010879:Piperazines