UNIGE document Scientific Article
previous document  unige:13275  next document
add to browser collection

Impact of antinucleants on transdermal delivery of testosterone from a spray

Leichtnam, Marie-Laure
Rolland, Hervé
Wüthrich, Patrick
Published in Journal of pharmaceutical sciences. 2007, vol. 96, no. 1, p. 84-92
Abstract The goal was to explore whether the incorporation of antinucleant polymers into a testosterone spray formulation could stabilize a putative supersaturated state and improve the delivery of the drug across the skin. Several antinucleants were screened using differential scanning calorimetry (DSC) and two candidates showed particular promise: a cyclodextrin derivative (RAMEB) and a vinylpyrrolidone/vinyl acetate copolymer (Kollidon VA64). These agents also improved significantly the long-term stability of saturated solutions of the drug. Further, using the method of mixed cosolvents, it was possible to create, in the presence of 5% w/v antinucleant polymer, supersaturated ethanol/propylene glycol/water (4:1:1 v/v) solutions of the drug with degrees of saturation between 1.4 and 2.6; however, these metastable systems existed only transiently under carefully controlled conditions and had reverted back to equilibrium solubilities of the drug within 6 h. When the same solutions were administered to hairless rat skin in vitro from mechanical sprays, no improvement in testosterone delivery, relative to a nonstabilized control, was observed. It appears, therefore, that the in situ crystallization process of the drug is more complex and incompletely understood (and cannot be predicted from DSC experiments). The complicated evaporation/volatilization process, which takes place when a spray is pulverized, requires better characterization before the use of supersaturation for testosterone delivery can be optimized.
Keywords Administration, CutaneousAerosolsAnimalsCalorimetry, Differential ScanningChemistry, PharmaceuticalCrystallizationCyclodextrins/chemistryDiffusion Chambers, CultureDrug StabilityExcipients/chemistry/pharmacologyMaleOrgan Culture TechniquesPermeabilityPyrrolidines/chemistryRatsRats, Inbred StrainsSkin Absorption/drug effectsTemperatureTestosterone/administration & dosage/chemistry/metabolismTime FactorsVinyl Compounds/chemistryViscosityVolatilization
PMID: 16998787
Full text
Article (Published version) (250 Kb) - document accessible for UNIGE members only Limited access to UNIGE
(ISO format)
LEICHTNAM, Marie-Laure et al. Impact of antinucleants on transdermal delivery of testosterone from a spray. In: Journal of pharmaceutical sciences, 2007, vol. 96, n° 1, p. 84-92. doi: 10.1002/jps.20670 https://archive-ouverte.unige.ch/unige:13275

510 hits

0 download


Deposited on : 2011-01-27

Export document
Format :
Citation style :