Drug migration from the adhesive matrix to the polymer film laminate facestock in a transdermal nitroglycerin system.
The apparent loss of nitroglycerin in a prototype transdermal nitroglycerin system was investigated by attenuated total reflectance infrared (ATR-IR) microspectroscopy and high performance liquid chromatography (HPLC). Several transdermal nitroglycerin lots placed under controlled storage conditions exhibited loss of drug potency (up to 10%) along with the appearance of a defect in the polymer film laminate facestock. A significant loss of nitroglycerin from the transdermal drug/adhesive matrix may reduce the bioavailabilty of nitroglycerin to the patient. ATR-IR analysis confirmed that nitroglycerin migrated from the drug/adhesive matrix to the facestock polyester layer under storage conditions and that nitroglycerin was retained in the facestock polyester layer. An alternate sample extraction solution successfully removed the nitroglycerin from both the adhesive matrix and facestock polyester layer with nearly 100% labeled strength recovered. The relationship between the migration of nitroglycerin into the facestock polyester layer and the appearance of the defect in the facestock aluminum layer is discussed and a nitroglycerin-aluminum metal reaction mechanism is proposed.
Markovich
R J
RJ
Department of Physical and Analytical Chemistry Research and Development, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. robert.markovich@spcorp.com
Taylor
A K
AK
Rosen
J
J
D000269:Adhesives / Q000032:analysis; D000279:Administration, Cutaneous; D000535:Aluminum / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D016503:Drug Delivery Systems; D004355:Drug Stability; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry; D011091:Polyesters / Q000032:analysis; D013055:Spectrophotometry, Infrared
D000269:Adhesives; D011091:Polyesters; D000535:Aluminum; D005996:Nitroglycerin