Impact of antinucleants on transdermal delivery of testosterone from a spray

Autor: Herve Rolland, Richard H. Guy, Patrick Wuthrich, Marie-Laure Leichtnam
Rok vydání: 2006
Předmět:
Male
Pyrrolidines
Time Factors
Vinyl Compounds
Chemistry
Pharmaceutical
Skin Absorption
Pharmaceutical Science
Pharmacology
Administration
Cutaneous
Polyvinyl alcohol
Permeability
law.invention
Excipients
chemistry.chemical_compound
Differential scanning calorimetry
Organ Culture Techniques
Drug Stability
law
Copolymer
Vinyl acetate
Animals
Testosterone
Crystallization
Transdermal
chemistry.chemical_classification
Aerosols
ddc:615
Supersaturation
Cyclodextrins
Calorimetry
Differential Scanning
Chemistry
Viscosity
Temperature
Skin Absorption/drug effects
Rats
Inbred Strains
Polymer
Rats
Vinyl Compounds/chemistry
Excipients/chemistry/pharmacology
Chemical engineering
Cyclodextrins/chemistry
Diffusion Chambers
Culture
Pyrrolidines/chemistry
Volatilization
Testosterone/administration & dosage/chemistry/metabolism
Zdroj: Journal of Pharmaceutical Sciences, Vol. 96, No 1 (2007) pp. 84-92
ISSN: 0022-3549
Popis: 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.
Databáze: OpenAIRE
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