title: In vitro release of fentanyl from transdermal patches in gastric and intestinal fluid.
abstract: CONTEXT. Fentanyl patches are intended for transdermal use to treat pain. However, these patches have been abused by ingestion, offering a unique mode of drug delivery with unknown drug release characteristics. OBJECTIVES. In vitro fentanyl release from patches in simulated gastric and intestinal fluid was evaluated. MATERIALS AND METHODS. Ten 75 mcg/hr fentanyl transdermal patches (Mylan Pharmaceuticals Inc., Morgantown, WV), simulated gastric fluid without enzymes, and USP simulated intestinal fluid (Ricca Chemical Company, Arlington, TX) were obtained. Each fentanyl patch was placed into either 100 mL of simulated gastric fluid or 100 mL of simulated intestinal fluid. Flasks were agitated at 24 rpm while incubated at 36.8°C. Fluid was sampled at time zero and 5, 15, 30, 60, 120, and 180 min after submersion. Fentanyl was assayed using ultra performance liquid chromatography coupled with tandem mass spectrometry (AIT Laboratories, Indianapolis, IN). RESULTS. An average of 239 mcg and 1,962 mcg of fentanyl was released into gastric fluid and 338 mcg and 3,139 mcg into intestinal fluid in 5 min and 3 h, respectively. An average of 26% and 41% of 7.65 mg of fentanyl contained within the 75 mcg/hr patch was released into gastric and intestinal fluid in 3 h, respectively (p = 0.169, Student's t-test). DISCUSSION. Our results demonstrate fentanyl release within 5 min of submersion. CONCLUSION. These results help support the potential rapid onset of clinical compromise reported and are relevant to the design of future pharmacokinetic studies of fentanyl release from transdermal patches.
authors.affiliation: Department of Medicine, Washington University in St. Louis School of Medicine , St. Louis, MO , USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Arroyo Plasencia
authors.forename: J
authors.initials: J
authors.lastname: Mowry
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Quigley
mesh_terms: D000279:Administration, Cutaneous; D016503:Drug Delivery Systems; D005283:Fentanyl / Q000493:pharmacokinetics*; D005750:Gastric Juice / Q000737:chemistry*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D016014:Linear Models; D057968:Transdermal Patch
chemical_list: D005283:Fentanyl
keywords: Fentanyl; Patch; Pharmacokinetics; Release; Simulated; Transdermal