System functionality and physicochemical model of fentanyl transdermal system

Abstract

Fentanyl is an opioid traditionally administered by infusion or injection and more recently in a rate-controlled transdermal dosage form. This system is a four-layer laminate on a protective liner. A backing layer seals and protects the drug reservoir, the source for continuous delivery of fentanyl. A membrane controls the release rate of fentanyl from the system. An adhesive layer attaches the system to skin and releases an initial loading dose of fentanyl. The rate of fentanyl delivery through skin is determined by the system and the skin at the application site. The release rate from the system is approximated by Fick's first law of diffusion and is controlled by the rate-controlling membrane. A complete simulation model that combines both in vitro release data and the pharmacokinetic model has been developed and used to show the influence of various physiologic and system variables on serum fentanyl concentrations.

Death by band-aid: fatal misuse of transdermal fentanyl patch

“…al. have reported that the application of the transdermal fentanyl patch to the broken skin can increase blood fentanyl concentrations by 5 times [15]. A similar case [6] included a 6-year-old, 27-kg girl admitted to the hospital in the morning due to the altered mental status after her grandfather applied the Durogesic 25 μg/h transdermal patch over abrasion on her back the evening before.…”

A safe and effective method for converting cancer patients from intravenous to transdermal fentanyl

“…9 Fentanyl is absorbed through a rate-limiting membrane by a process of passive cutaneous diffusion when administered by the transdermal route. 10 The drug forms a depot within the skin before entering the microcirculation and, as a result, exhibits delayed pharmacokinetic properties. 1-2 Therapeutic fentanyl blood levels are reached approximately 12-16 hours after the initial application of transdermal fentanyl patches.…”

Transdermal fentanyl: Pharmacology and toxicology

“…For example, variations in skin thickness and degree of keratinization will alter its systemic bioavailability and account for much of the great interindividual variability observed with transdermal fentanyl absorption [41][42][43]. This can be seen in Figure 2, in which there is a wide range around the mean serum fentanyl concentration in transdermal fentanyl users.…”

“…Skin surface areas with similar stratum corneum thickness typically possess similar diffusion rates within an individual, explaining why the chest, extremities, and abdomen are acceptable sites for transdermal device application without the need for any dosage changes [41,44]. Following application of a transdermal fentanyl device to broken skin, blood fentanyl concentrations can rise 5-fold [42]. Exposed tissue lacking a stratum corneum, such as mucosa, has a >30-fold increase in fentanyl absorption, and more predictable pharmacokinetics [45].…”

“…An increase in skin temperature from 32°C to 40°C leads to a gradual 10-to 15-fold increase in cutaneous blood flow [54]. A 3°C increase in body temperature raises the peak fentanyl blood concentration by 25% [42]. Case reports detail that elevation in skin or ambient temperatures from external sources such as hot tubs or heating blankets may lead to fentanyl overdose [4, 37,55,56].…”