title: Transdermal delivery of zidovudine (AZT): the effects of vehicles, enhancers, and polymer membranes on permeation across cadaver pig skin.
abstract: The purpose of this study was to investigate the effects of vehicles, enhancers, and polymer membranes on 3'-azido-3'-deoxythymidine (AZT) permeation across cadaver pig skin. Four binary vehicles (ethanol/water, isopropyl alcohol/water, polyethylene glycol 400/water, and ethanol/isopropyl myristate [IPM]) were tested for AZT solubility and permeability across pig skin; ethanol/IPM (50/50, vol/vol) demonstrated the highest AZT flux (185.23 microg/cm2/h). Next, the addition of various concentrations of different enhancers (N-methyl-2-pyrrolidone [NMP], oleic acid, and lauric acid) to different volume ratios of ethanol/IPM was investigated for their effect on AZT solubility and permeability across pig skin. The use of 2 combinations (ethanol/IPM [20/80] plus 10% NMP and ethanol/IPM [30/70] plus 10% NMP) resulted in increased AZT solubility (42.6 and 56.27 mg/mL, respectively) and also high AZT flux values (284.92 and 460.34 microg/cm2/h, respectively) without appreciable changes in lag times (6.25 and 7.49 hours, respectively) when compared with formulations using only ethanol/IPM at 20/80 and 30/70 volume ratios without addition of the enhancer NMP. Finally, AZT permeation across pig skin covered with a microporous polyethylene (PE) membrane was investigated. The addition of the PE membrane to the pig skin reduced AZT flux values to 50% of that seen with pig skin alone. However, the AZT flux value attained with ethanol/IPM (30/70) plus 10% NMP was 215.31 microg/cm2/h, which was greater than the target flux (208 mug/cm2/h) needed to maintain the steady-state plasma concentration in humans. The results obtained from this study will be helpful in the development of an AZT transdermal drug delivery system.
authors.affiliation: The Government Pharmaceutical Organization, Rama VI Road, Ratchatewi, Bangkok 10400, Thailand. snuntakan@yahoo.com
authors.forename: Nuntakan
authors.initials: N
authors.lastname: Suwanpidokkul
authors.forename: Phensri
authors.initials: P
authors.lastname: Thongnopnua
authors.forename: Kaisri
authors.initials: K
authors.lastname: Umprayn
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002102:Cadaver; D016503:Drug Delivery Systems / Q000379:methods*; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D015215:Zidovudine / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D011108:Polymers; D015215:Zidovudine