Transdermal-controlled administration

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... 

Tien, J.H. Transdermal-controlled administration of oxycodone. J.Pharm.Sci., 1991, 80, 741-743... 

Kuo PC, Liu JC, Chang SF and Chien YW, In vitro transdermal permeation of oxycodone. I. Effect of pH, delipidation and skin stripping, Drug Dev. Ind. Pharm., 15,1199-1215 (1989). NB No further details given. Value was repeated in Tien J-H., Transdermal-controlled administration of oxycodone, /. Pharm. Set, 80, 741-743 (1991) Lombardo F, Obach RS, Shalaeva MY and Gao F, Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics, /. Med. Chem., 47,1242-1250 (2004). 

International Pharmaceutical R D Symposium on Advances in Transdermal Controlled Drug Administration for Systemic Medications, Rutgers University, College of Pharmacy, June 20 21, 1985. 

Chien, Y. W. (1983), Logics for transdermal controlled drug administration, Drug Dev. Ind. Pharm., 9, 497-520. 

Transdermal administration can avoid first-pass metabolism as well as provide a large surface area for continuous-controlled administration of drugs with short biological half-lives and narrow therapeutical indices. The route has been used for nitroglycerin ointments, and transdermal therapeutical systems (patches) have been developed for scopolamine, nitroglycerin, clonidine, estradiol, and nicotine. 

Chien, Y.W. International Pharmaceutical R D Symposium on Advances in Transdermal Controlled Drug Administration for Systemic Medication. Piscataway, New Jersey, June 20 21, 1985 Rutgers University, College of Pharmacy, Proceedings Published in Transdermal Controlled Systemic Medications Chien, Y.W., Ed. Marcel Dekker, Inc. New York, 1987. 

In membrane diffusion systems the polymer membrane with a given pore size or pore size distribution controls the diffusion of the active substance from the drug reservoir. Dosage forms with membrane-controlled drug delivery can be coated tablets, coated granules or pellets, or so-called multiparticulate systems on which various coats are applied. One possibility for transdermal drug administration is the transdermal patch controlled with a membrane [4-7,34-39]. 

Membrane-controlled Transdermal Drug Administration Drug administration through the intact skin, transdermal therapy, was realized at the end of the 20th century with the development of transdermal therapeutic systems [22, 59]. Various polymers are necessary for this. 

Transdermal Drug Administration Controlled with Matrix Diffusion Drug administration through the skin was first achieved with hydrogel-type patches, that are polymer matrixes [4,22,61,75]. Matrix diffusion is characteristic... 

These include atropine, scopolamine (hyoscine), trihexyphenidyl (benzhexol) and benzatropine. They block central muscarinic receptors involved in various afferent pathways of the vomiting reflex (Fig. 1). They have been used to control motion sickness, emesis in Meniere s disease and postoperative vomiting. Currently, hyoscine is largely restricted to the treatment of motion sickness where it has a fast onset of action but a short duration (4-6 h). Administration of hyoscine by transdermal patch produces a prolonged, low-level release of the drug with minimal side effects. To control postoperative vomiting, it should be applied >8 h before emesis is anticipated. 

As pharmaceutical scientists gain experience and tackle the primary challenges of developing stable parenteral formulations of proteins, the horizons continue to expand and novel delivery systems and alternative routes of administration are being sought. The interest in protein drug delivery is reflected by the wealth of literature that covers this topic [150-154]. Typically, protein therapeutics are prepared as sterile products for parenteral administration, but in the past several years, there has been increased interest in pulmonary, oral, transdermal, and controlled-release injectable formulations and many advances have been made. Some of the more promising recent developments are summarized in this section. 

Perioperative use Continue administration of clonidine to within 4 hours of surgery and resume as soon as possible thereafter. Carefully monitor blood pressure and institute appropriate measures to control it. If transdermal therapy is started during the perioperative period, note that therapeutic plasma levels are not achieved until 2 to 3 days after initial application. 

Nitrates are required for symptomatic relief of chest pain they are not proven to improve hard outcomes such as MI or death. Nitrates should be given initially sublingually or by spray, followed by oral or transdermal routes if pain is relieved. Lack of pain relief mandates i.v. administration. Beta-blockers such as metoprolol are used and may reduce the risk of subsequent MI. Calcium channel blockers such as dilfiazem, verapamil, or long-acting di-hydropyridines can be added for symptom control if nitrates and beta-blockers do not suffice they do not improve outcomes. In fact, they may worsen outcomes in the presence of left ventricular dysfunction or CHF in acute coronary syndrome. 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

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. 

Transdermal delivery is a noninvasive intravenous infusion of drug to maintain efficacious drug levels in the body for predictable and extended duration of activity. Diffusion-controlled transdermal systems are designed to deliver the therapeutic agent at a controlled rate from the device to and through the skin into the systemic circulation. This route of administration avoids unwanted presystemic metabolism (first-pass effect) in the GI tract and the liver. Patient satisfaction has been realized through decreased... 

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