Permeation, stability and acute dermal irritation of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica crude extract loaded transdermal gels

Abstract

In this study, permeation behaviors and chemical stability of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica (PM), Thai traditional medicine, crude extract containing transdermal gels were firstly evaluated. Three different PM extract containing gels were formulated, including hydroalcoholic and microemulsion gels using carbomer, and silicone gel using silicone elastomer. In vitro permeation through porcine ear skin demonstrated that the flux and 24 h cumulative permeation of miroestrol and deoxymiroestrol were in the order of hydroalcoholic > silicone > microemulsion gels. Hydroalcoholic gel provided the highest partition coefficient from gel onto skin, and thus the skin permeability coefficient. After 24 h permeation, no miroestrol and deoxymiroestrol remained deposited in the skin. Accelerated study using heating-cooling revealed insignificant difference between the remaining percentages of miroestrol and deoxymiroestrol in aqueous and non-aqueous based gels. Long-term stability study showed that miroestrol contents remained constant for 90 d and 30 d under 5 ± 3 °C and 30 ± 2 °C, 75 ± 5%RH, respectively; whereas the percentage of deoxymiroestrol decreased significantly after 30 d storage, irrespective of storage conditions. Acute dermal irritation test on New Zealand White rabbits showed that PM hydroalcoholic gels were non-irritant, with no signs of erythema or oedema.