Transdermal and dermal delivery of adefovir: effects of pH and permeation enhancers
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18248973
DOI
10.1016/j.ejpb.2007.12.005
PII: S0939-6411(07)00410-9
Knihovny.cz E-resources
- MeSH
- Adenine administration & dosage analogs & derivatives pharmacokinetics MeSH
- Antiviral Agents administration & dosage pharmacokinetics MeSH
- Administration, Cutaneous MeSH
- Hydrogen-Ion Concentration MeSH
- Skin Absorption drug effects MeSH
- Humans MeSH
- Organophosphonates administration & dosage pharmacokinetics MeSH
- Permeability MeSH
- Excipients MeSH
- Solvents MeSH
- Drug Delivery Systems MeSH
- In Vitro Techniques MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- adefovir MeSH Browser
- Adenine MeSH
- Antiviral Agents MeSH
- Organophosphonates MeSH
- Excipients MeSH
- Solvents MeSH
The objective of this work was to investigate feasibility of transdermal and dermal delivery of adefovir (9-(2-phosphonomethoxyethyl)adenine), a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. Transport of 2% adefovir through and into porcine skin and effects of various solvents, pH, and permeation enhancers were studied in vitro using Franz diffusion cell. From aqueous donor samples, adefovir flux through the skin was 0.2-5.4 microg/cm2/h with greatest permeation rate at pH 7.8. The corresponding adefovir skin concentrations reached values of 120-350 microg/g of tissue. Increased solvent lipophilicity resulted in higher skin concentration but had only minor effect on adefovir flux. A significant influence of counter ions on both transdermal and dermal transport of adefovir zwitterion was observed at pH 3.4. Permeation enhancer dodecanol was ineffective, 1-dodecylazepan-2-one (Azone) and dodecyl 2-(dimethylamino)propionate (DDAIP) showed moderate activity. The highest adefovir flux (11.3+/-3.6 microg/cm2/h) and skin concentration (1549+/-416 microg/g) were achieved with 1% Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate) at pH 4. This study suggests that, despite its hydrophilic and ionizable nature, adefovir can be successfully delivered through the skin.
References provided by Crossref.org
Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery
