Transdermal delivery of buprenorphine through cadaver skin.
The skin permeation of buprenorphine base and HCl salt through cadaver skin was investigated. The octanol-water partition coefficient and solubilities of both buprenorphine free base and HCl salt were determined at 32 degrees C. As expected, buprenorphine free base was more lipophilic than its HCl salt and was practically insoluble in aqueous buffer 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.HCl was significantly higher than that of the free base from propylene glycol/lauric acid vehicle mixtures. Buprenorphine base permeation through tape-stripped epidermis suggested that in addition to stratum corneum, viable epidermis presented a significant diffusion barrier because of the very low aqueous solubility of the free base observed. The mean steady-state skin fluxes of buprenorphine.HCl were 20.3 and 29.7 micrograms/cm2/h from propylene glycol:lauryl alcohol: ethanol (80:15:5) and propylene glycol: propylene glycol monolaurate: water (80:15:5) vehicle mixtures, respectively. The skin flux of buprenorphine.HCl from various monolithic matrix patches was also evaluated. When capric acid, lauric acid, and lauryl alcohol were separately incorporated into an adhesive matrix, the skin flux of buprenorphine.HCl was enhanced by a factor of 2 to 3.5. Finally, based on the total body clearance and minimum effective concentration of buprenorphine, a transdermal delivery rate of 2.5 micrograms/cm2/h from a 20-cm2 patch was estimated. The in vitro skin permeation data clearly suggest that transdermal delivery of buprenorphine is feasible to achieve a desired systemic analgesic effect.
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Cygnus Therapeutic Systems, Redwood City, CA 94306.
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D000279:Administration, Cutaneous; D002047:Buprenorphine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D014677:Pharmaceutical Vehicles; D002047:Buprenorphine