Transdermal delivery of zidovudine (AZT): the effects of vehicles, enhancers, and polymer membranes on permeation across cadaver pig skin.
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.
Suwanpidokkul
Nuntakan
N
The Government Pharmaceutical Organization, Rama VI Road, Ratchatewi, Bangkok 10400, Thailand. snuntakan@yahoo.com
Thongnopnua
Phensri
P
Umprayn
Kaisri
K
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
D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D011108:Polymers; D015215:Zidovudine