Optimization ofin VitroFlux Through Hairless Mouse Skin of Cidofovir, a Potent Nucleotide Analog
| Autor: | Elena Aspe, William A. Lee, Richard H. Guy, Gary C. Visor, James A. Kennedy, Richard D. Ennis |
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| Rok vydání: | 1995 |
| Předmět: |
Stereochemistry
Skin Absorption viruses Organophosphonates Pharmaceutical Science In Vitro Techniques Antiviral Agents Dosage form Cytosine Mice chemistry.chemical_compound Organophosphorus Compounds Stratum corneum medicine Animals Mice Hairless Chromatography Aqueous solution Isopropyl alcohol Penetration (firestop) Hairless Oleic acid medicine.anatomical_structure Solubility chemistry Pharmaceutical Vehicles Gels Cidofovir |
| Zdroj: | Journal of Pharmaceutical Sciences. 84:750-754 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.2600840617 |
| Popis: | The in vitro flux (4-8 h) of cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) was measured across full-thickness hairless mouse skin to evaluate potential formulations for local treatment of herpes virus infections. The effects of propylene glycol, isopropyl alcohol, oleic acid, pH, and cidofovir concentration were examined. In addition, several prototype aqueous gel formulations were studied. Flux values (4-8 h) increased linearly with cidofovir concentration in both solution and gel formulations. Removal of the stratum comeum by tape stripping increased the flux by approximately 400-fold, whereas pH (4.5 versus 7) had little effect on flux. The presence of propylene glycol, isopropyl alcohol, or their combination did not significantly increase mean flux (por = 0.05). Pretreatment of the skin with oleic acid resulted in a significant enhancement of cidofovir flux (por = 0.01). From the measured flux values, the calculated concentration of cidofovir achievable in the viable epidemis from a 1% cidofovir gel formulation was approximately 14 micrograms/mL, which is comparable to the in vitro 50% inhibitory dose (ID50) values for herpes simplex viruses HSV-1 and HSV-2. |
| Databáze: | OpenAIRE |
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