Reservoir based fentanyl transdermal drug delivery systems: effect of patch age on drug release and skin permeation.
OBJECTIVE
To understand and evaluate the stability and skin permeation profiles of fentanyl reservoir systems as a function of patch age.


METHODS
Drug release and skin permeation studies were performed using a modified USP apparatus 5 with a novel sample preparation technique.


RESULTS
The amount of fentanyl present in the EVA/adhesive layer (EAL) increased from about 17% of label claim (LC) at 5 months to 25% LC at 22 months. The increase in the drug concentration was mainly observed in the peripheral EAL. Simultaneously, the alcohol content of the patch decreased as a function of patch age. A significant effect of patch age on the drug content in the EAL and the drug release from the system was observed; however, skin permeation studies did not indicate an increase in drug delivery rate.


CONCLUSIONS
Novel sample preparation technique with USP Apparatus 5 allowed determination of in vitro skin permeation rates for fentanyl transdermal patches with different designs. Permeation rates with cadaver skin as substrate were found not to change with patch age despite changing drug concentration in the EAL.
Prodduturi
Suneela
S
Division of Pharmaceutical Analysis, U.S. Food and Drug Administration, 1114 Market Street, St. Louis, MO 63101, USA. suneela.prodduturi@fda.hhs.gov
Smith
Glen J
GJ
Wokovich
Anna M
AM
Doub
William H
WH
Westenberger
Benjamin J
BJ
Buhse
Lucinda
L
D000759:Adjuvants, Anesthesia / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000438:Alcohols / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D005283:Fentanyl / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008567:Membranes, Artificial; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D013997:Time Factors
D000759:Adjuvants, Anesthesia; D000438:Alcohols; D008567:Membranes, Artificial; D005283:Fentanyl