Artigo traduzido

1- Although each system offers an unlimited number of sample formulations, we selected a representative W/O and O/W formulation from system 1 to test transdermal delivery of hydrophilic and hydrophobic drugs across stripped human skin. The results (Table III) indicate that the O/W system provided significantly better flux for all the drugs studied (p < 0.025). The simultaneous delivery of estradiol with diltiazem HCl from the ME system did not affect the transport of either drug (p > 0.5, Table IV). Interestingly, the drug permeability from a homogenous single phase composed of all the water-soluble components is similar to drug flux from O/W ME (p > 0.25). This suggests that the oil phase in our formulation serves as a depot for the drug, while the drug transport occurs primarily from the water phase. This phenomenon could have significant implications for the development of transdermal systems for long-term sustained delivery.

2- For all the drugs tested, the ME systems provided sig-nificant enhancement (Table V). The finding that flux is im-proved in O/W formulations as compared with W/O systems even for the hydrophobic drugs suggests that transport from the aqueous phase is key. When the organic phase and sur-factants were removed from the ME, leaving only the water phase components (H2O, ethanol, NMP), the flux was com-parable to that from the O/W ME (Table IV). Previous work indicates that the H2O/NMP synergy provides greater trans-dermal flux enhancement than H2O/ethanol. Although the complexity of the multiple components in the system makes it difficult to determine the exact molecular interactions, it ap-pears that the presence of NMP in the water phase plays a key role in the transport of hydrophobic drugs from an O/W ME.

3- It has been suggested that ME transdermal enhancement is a result of increasing drug concentration in the donor phase (2). In our systems containing the chemical enhancer NMP, we believe that the effective permeability of the