Enhanced skin permeation of piroxicam and pranoprofen induced from nanoparticles dispersed in propylene glycol aqueous solution

Abstract

The effects of water-soluble polymers on nanoparticle formation of piroxicam and pranoprofen were investigated. We also studied the effects of propylene glycol (PG) concentration in PG aqueous solution on skin permeation of the drugs from nanoparticles. Physical mixtures (PMs) of the drug, hydroxypropylmethylcellulose (HPMC), and sodium dodecyl sulfate (SDS) (weight ratio, 1:3:1) were ground for 90 min in a vibrational rod mill to prepare ground mixtures (GMs). The particle sizes of the GM suspensions in distilled water were 76 nm for piroxicam and 146 nm for pranoprofen, respectively. It was found that the permeation of piroxicam and pranoprofen through hairless mouse skin was significantly increased when the ternary GMs were suspended in PG aqueous solution; however, no enhanced permeation was observed with drug/HPMC binary GMs. Because the piroxicam/SDS binary GM caused skin damage, a ternary GM was critical for increasing the skin permeation of poorly water-soluble drugs. The skin permeation of piroxicam and pranoprofen could be attributed to their supersaturation in suspension due to nanoparticle formation. The skin permeation of piroxicam from the GM suspension was independent of PG concentration in PG aqueous solution, but that of pranoprofen increased with PG concentration in PG aqueous solution. This difference can be attributed to the different solubilities of piroxicam and pranoprofen in PG aqueous solution.