TRANSDERMAL DELIVERY OF BUPRENORPHINE THROUGH CADAVER SKIN

The skin permeation of buprenorphine base and HCI salt through cadaver skin was investigated. The octanol-water partition coefficient and so lubilities of both buprenorphine free base and HCI salt were determine d at 32 degrees C. As expected, buprenorphine free base was more lipop hilic than its HCI salt and was practically insoluble in aqueous buffe r at pH 8.7. The drug solubility decreased exponentially as the pH of the solution increased, whereas the permeability coefficient increased as the donor solution pH decreased. The skin flux of buprenorphine.HC I was significantly higher than that of the free base from propylene g lycol/lauric acid vehicle mixtures. Buprenorphine base permeation thro ugh tape-stripped epidermis suggested that in addition to stratum corn eum, viable epidermis presented a significant diffusion barrier becaus e of the very low aqueous solubility of the free base observed. The me an steady-state skin flues of buprenorphine HCI were 20.3 and 29.7 mu g/cm(2)/h from propylene glycol:lauryl alcohol:ethanol (80:15:5) and p ropylene glycol:propylene glycol monolaurate:water (80:15:5) vehicle m ixtures, respectively. The skin flux of buprenorphine HCI from various monolithic matrix patches was also evaluated. When capric acid, lauri c acid, and lauryl alcohol were separately incorporated into an adhesi ve matrix, the skin flux of buprenorphine HCI was enhanced by a factor of 2 to 3.5. Finally, based on the total body clearance and minimum e ffective concentration of buprenorphine, a transdermal delivery rate o f 2.5 mu g/cm(2)/h from a 20-cm(2) patch was estimated. The in vitro s kin permeation data clearly suggest that transdermal delivery of bupre norphine is feasible to achieve a desired systemic analgesic effect.