Purpose:
To develop an ethylene-vinyl acetate (EVA matrix system
containing a permeation enhancer for enhanced
transdermal delivery of torasemide.
Methods:
The
solubility of torasemide was studied at various volume
fraction of polyethylene glycol (PEG) 400. The effect of
drug concentration was tested at 1.0, 2.0 and 3.0 %,
respectively while the effect of temperature on drug
release from drug-EVA matrix was evaluated at 27, 32, 37
and 42 oC. To increase pore size and
flexibility of the EVA matrix, plasticizers with citrate
and phthalate groups were added to the matrix containing
torasemide. To improve the penetration of torasemide
from the EVA matrix across the skin, enhancers
(propylene glycol derivatives, fatty acids, glycerides,
pyrrolidones and non-ionic surfactants) were
incorporated into the torasemide-EVA matrix. The effects
of the enhancers on the skin penetration were evaluated
using Franz diffusion cell fitted with the intact
excised rat skin.
Results:
Solubility and permeation of torasemide was highest at
40 %v/v PEG 400. The release rate of drug from drug-EVA
matrix increased with increased loading dose and
temperature. Release rate was proportional to the square
root of loading dose. The activation energy (Ea),
which was derived from the slope of log P versus 1000/T,
was 14.95 kcal/mol for 2.0% loading dose. Among the
plasticizers used, diethyl phthalate showed the highest
release rate of torasemide. Among the enhancers used,
polyoxyethylene 2-oleyl ether showed the greatest
enhancing effect.
Conclusion:
For the enhanced controlled transdermal delivery of
torasemide, the application of the EVA matrix containing
plasticizer and penetration enhancer could be useful in
the development of a transdermal drug delivery system.
Keywords:
Torasemide, Ethylene-vinyl acetate, Controlled
transdermal delivery, Matrix, Plasticizer, Permeation
enhancer.
