Controlled Transdermal Delivery of Fentanyl: Characterizations of Pressure-Sensitive Adhesives for Matrix Patch Design

Abstract

Transdermal delivery of fentanyl from various adhesive matrix formulations to achieve a steady-state skin flux was investigated. For this purpose, various pressure-sensitive adhesives selected from the three chemical classes of polymers (polyisobutylene (PIB), acrylate, and silicone adhesives) were characterized with respect to fentanyl's solubility, diffusion coefficient, and permeability coefficient. The solubility of fentanyl in various pressure-sensitive adhesives at 32 degrees C was determined by the drug absorption-desorption method. The solubilities of fentanyl in these adhesives were in the following order: acrylate > silicones > PIB. The permeability coefficient and diffusion coefficient of fentanyl in these adhesives were determined by the membrane diffusion method. The diffusion coefficient rank order was silicone-2920 > silicone-2675 > or = acrylate > PIB. The release profiles of fentanyl in the aqueous buffer from these adhesives with 2-4% drug loading was evaluated. The release rate of fentanyl from the acrylate polymer was significantly higher than those of silicone and PIB adhesives. The in vitro flux of fentanyl through cadaver skin from various adhesives with 2% drug loading was determined at 32 degrees C using modified Franz diffusion cells. The skin fluxes of fentanyl from silicone-2920 and PIB adhesives were 6.3 +/- 0.7 and 3.1 +/- 0.3 micrograms/cm2/h, respectively. On the other hand, the skin fluxes of fentanyl from acrylate and silicone-2675 adhesive matrices were about 1 microgram/cm2/h. The effect of drug loading on skin flux was investigated using PIB as a model adhesive. The drug released in the phosphate buffer (pH = 6.0) increased linearly as the drug loading in the PIB was increased from 1% to 4%; and as the drug loading exceeded 4%, an initial burst effect followed by a zero-order release was observed. The skin flux of fentanyl increased proportionally as the drug loading in the PIB adhesive was increased from 1 to 4%, and a plateau was reached beyond 4% drug loading. These results suggest that fentanyl concentration in the PIB adhesive might have reached saturation above 4% drug loading and that the optimum skin flux was accomplished from such a system because of attainment of maximum thermodynamic activity.

Confocal Raman investigation of diffusion processes in monolithic type transdermal drug delivery systems

“…The lowest diffusion coefficient was observed for the rubberbased matrix. The order of silicone4acrylate4rubber was also reported by Roy et al (1996) for the diffusion of fentanyl. Paeonol diffusion measured in porcine stratum corneum was much lower than in the adhesives with a coefficient of 2.85 Â 10 À16 m 2 /s.…”

“…Already published data by Cantor (1999) and Roy et al (1996) were in the same order of magnitude (Table 1). The diffusion coefficient in the silicone adhesive BIO-PSA 7-4202 of Paeonol was the highest followed by the diffusion coefficient in the acrylic adhesive.…”

“…Sato et al (2001) proposed a solubility factor for the prediction of drug fluxes during application of TDDSs on skin. Roy et al (1996) used the solubility and the diffusion coefficient to predict the release properties of transdermal delivery systems with fentanyl. Therefore, they investigated acrylic-, rubber-and silicone-based adhesives.…”

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

“…This work helped draw drug potency into the transdermal delivery picture. During this period, Gordon had a short stint at Cygnus and contributed to a key paper comparing suitable adhesive patches for the transdermal delivery of fentanyl [64]. This carefully conducted study showed that optimal and prolonged fentanyl human skin fluxes from different transdermal patches could be reached on attainment of maximum thermodynamic activity (fig.…”

“…10 Human skin flux of fentanyl from poly-isobutylene (PIB) transdermal adhesive matrices at 32°C for a range of fentanyl loadings [64]. …”