Transdermal delivery of sodium nonivamide acetate from volatile vehicles: effects of polymers

The permeation of sodium nonivamide acetate (SNA), a newly designed analogue of capsaicin, from ethanol/pH 4.2 buffer solutions containing antinucleant polymers across rat skin, was investigated. The in vitro release of SNA was determined under an open condition at 25 degrees C and 65% relative humidity. Therefore, the influence of the evaporation of vehicle components on the permeation of SNA was examined. Evaporation of the vehicle led to so drastic compositional changes that supersaturation is attained quickly. However, supersaturated solutions started to crystallize reducing the thermodynamic activity of SNA. Antinucleant polymers were used in the preparation of volatile vehicles in order to maintain the increased activity state of the drug. Methyl cellulose (MC) and hydroxypropyl cellulose (HPC) were both the efficient antinucleant polymers to increase the permeation of SNA. The permeation of SNA determined from volatile vehicles with 2% MC showed the result that the flux of SNA reached maximum at a certain ethanol proportion. A part of ethanol in the vehicle may penetrate into the skin causing the dehydration of stratum corneum and, therefore, the reduction of SNA permeation. The permeation of SNA was increased when ethanol in the volatile vehicle was replaced by n-propanol which could be due to the increased SNA solubility and reduction of diffusional barrier of stratum Corneum in the presence of n-propanol. (C) 1999 Elsevier Science B.V. All rights reserved.