Transdermal delivery system fentanyl

Koo PJ. Postoperative pain management with a patient-controlled transdermal delivery system for fentanyl. Am J Health Syst Pharm. 2 00 5 62 1171-1176. 

Fentanyl transdermal delivery systems (FTDS) use an unsealed multilaminate system containing a solid matrix, in which fentanyl is embedded instead of the reservoir designed in the TTS. FTDS is not to be recommended for routine postoperative pain treatment, even though it has a faster onset of action (4—6 hours) after cases of fentanyl toxicity, especially respiratory depression. FTDS has not been investigated adequately in chronic pain and is not expected to be superior to the TTS technique. 

J. M. Prosser, B. E. Jones and L. Nelson, Complications of oral exposure to fentanyl transdermal delivery system patches, J. Med. Toxicol., 2010, 6, 443 47. 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

The transdermal system provides continuous systemic delivery of fentanyl for 72 h. The amount of drug released from the system per hour is proportional to the surface area. Following application of the patch to the skin, a depot of fentanyl concentrates in the upper skin layers. This is then available to the systemic circulation. There is an initial rise in blood fentanyl concentration after application followed by a leveling off that occurs 12 to 24 h later. Peak blood concentrations occur between 24 and 72 h after application. The skin does not appear to metabolize fentanyl when delivered transdermally. 

Iontophoresis techniques (i.e., the use of electric current to facilitate transdermal delivery) have also been advocated as a way to enhance transdermal opioid delivery to the systemic circulation.11 By varying the amount of electric current, iontophoresis may ultimately allow the patient to control the rate of transdermal administration of the opioid.10,76,78 Finally, certain opioids such as fentanyl can be administered systemically via lozenges or a lollipop that dissolves in the mouth (transmucosal delivery), or via nasal spray (intranasal administration).21,54 It will be interesting to see if these newer methods of administration will gain widespread acceptance in the future. 

Patient controlled transdermal analgesia (PCTA) is one of the newest variations on PCA. PCTA uses a delivery system consisting of a small patch that is approximately the size of a credit card.29,45 This patch is adhered to the patient s skin, usually on the arm or upper chest. The patch is impregnated with an opioid such as fentanyl, and the patient can self-administer a... 

Another product that uses iontophoresis has been recently approved by the FDA. This device is called Ionsys and is an iontophoretic system that delivers fentanyl hydrochloride transdermally [37, 38], This is a patient-controlled device that provides on-demand delivery of fentanyl for up to 24 h or 80 doses. This device contains 10.8 mg of fentanyl hydrochloride and is designed to deliver a 40-pg dose of fentanyl over a 10-min period upon activation of the dose button by the patient. 

Generic Name iontophoretic transdermal fentanyl delivery system Trade/Proprietary Name lONSYS ... 

Other than possibly for the insensible perspiration they absorb, transdermal patches tend to operate as thermodynamically static systems, meaning as com-positionally fixed systems, from the moment they are applied until their removal. Marketed ethanol-driven estradiol and fentanyl patches are exceptions because they meter out ethanol and drive it into the stratum corneum to propel the absorption process. Compositional steadfastness is still the rule, however, and it is this feature that bestows the zero-order delivery attribute on the ordinary transdermal patch. Drug is present within the patches in reservoir amounts whether or not the reservoir compartment is easily distinguished, for there must be enough drug to sustain delivery over the full course of patch wear. 

Parenteral (generic, Sublimaze) 50 mcg/mL for injection Fentanyl Transdermal System (Duragesic) 12.5, 25, 50, 75, 100 mcg/h delivery Fentanyl Buccal 100, 200, 400, 600, 800 meg oral lozenge Fentanyl Actiq 200, 400, 600, 800, 1200, 1600 meg lozenge on a stick Patient Controlled Transdermal Iontophoretic Fentanyl System 40 meg per dose for delivery Hydromorphone (generic, Dilaudid)... 

Dosages and routes of administration For acute (postoperative) pain and for anesthesia, fentanyl is given by the intravenous route. For pre-medication in anesthesia and for break-through pain the compound can also been given as an oral-transmucosal formulation (Ashburn and Streisand, 1994). A transdermal patch has been developed for chronic pain treatment (Jeal and Benfield, 1997 O Siordin, 1998). The intravenous doses for premedication are 50-100 pg, oral-transmucosal systems contain 200-400 pg and patch formulations have a delivery rate of 25-100 pg/h. 

The same technology has been utilized in the development of the following 1) the Estraderm system, which administers a controlled dose of estradiol transdermally over 3 days for the relief of postmenopausal syndrome and osteoporosis 2) the Duragesic system, which provides a transdermal-controlled administration of fentanyl, a potent narcotic analgesic, for 72-h relief of chronic pain and 3) the Androderm system, which provides a transdermal-controlled delivery of... 

Membrane permeation-controlled transdermal drug delivery (Fig. 5.2) has been successfully applied in therapeutic systems for scopolamine (prevention of motion sickness for a 3-day period), nitroglycerin (prophylaxis against attack of angina pectoris over a 24-h period), clonidine (control of hypertension for a 7-day period), and fentanyl (control of constant pain for 72 h). 

Panchal and coworkers evaluated the incidence of analgesic gaps resulting from SREs for patients using the fentanyl iontophoretic transdermal system (ITS), a non-invasive PCA system, or morphine IV-PCA for post operative pain management [12]. For morphine IV-PCA, infiltration of the IV line was the most frequently reported SRE that resulted in an analgesic gap. Infiltration at the catheter site is a problem commonly encoimtered with IV-related procedures, and may result in IV line failure and/or a subcutaneous depot of opioid, leading to inadequate and ineffective delivery... 

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