Modified water containing hydrophilic ointment with suspended hydrocortisone-21-acetate--the influence of the microstructure of the cream on the in vitro drug release and in vitro percutaneous penetration.
Water containing hydrophilic ointment DAB 1997 was modified by the incorporation of ethanol and the effects of ethanol on the evaporation, the drug liberation and the permeation through human excised stratum corneum were investigated. Creams with 10%, 20%, 30% (v/v) and without ethanol were produced. As a model drug 2% (w/w) hydrocortisone-21-acetate was suspended in the o/w cream. The evaporation of the creams decreased with an increasing amount of ethanol which was unexpected because the vapor pressure of ethanol is higher than that of water. From this result it was concluded that ethanol might be interlamellarly fixed in the mixed crystal of the polyhydrate of the emulsifier to a higher extent than it is distributed within the aqueous bulk phase. In context with the liberation studies, ethanol decreased the drug liberation from the cream. This is in accordance with the above hypothesis of the ethanol partitioning within the cream, because the solubility of the drug in ethanol is higher than that in water. Therefore the interlamellar drug concentration should be higher than the solubility of the drug in the bulk phase, with the assumption that the gel network of the emulsifier polyhydrate is finally responsible for the delay in drug liberation. The permeation through stratum corneum showed no significant differences between the alcohol-free and the alcohol-loaded formulations. Obviously the decrease in drug liberation by ethanol was compensated for by the penetration enhancing effect.
Müller-Goymann
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CC
Technische Universität Carolo-Wilhelmina zu Braunschweig, Institut für Pharmazeutische Technologie, Germany. c.mueller-goymann@tu-bs.de
Alberg
U
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D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009824:Ointments; D010539:Permeability; D013535:Suspensions
D000893:Anti-Inflammatory Agents; D009824:Ointments; D013535:Suspensions; C021650:hydrocortisone acetate; D006854:Hydrocortisone