Transdermal administration

Transdermal Administration. The development of the stratum corneum is complete at birth and is considered to have permeability similar to that of adults, except in preterm infants [81], Preterm neonates and infants have an underdeveloped epidermal barrier and are subject to excessive absorption of potentially toxic ingredients from topically applied products. 

The absorption rate of drugs administered as intramuscular or subcutaneous injections may be affected in elderly because of reduced tissue blood perfusion. This is also true for transdermal administration, e.g. patches and gels, of drugs (Turnheim 2003). 

J. E. Riviere, J. D. Brooks, P. L. Williams, E. McGown, M. L. Francoeur, Cutaneous Metabolism of Isosorbide Dinitrate after Transdermal Administration in Isolated Perfused Porcine Skin , Int. J. Pharm. 1996, 127, 213-217. 

Transdermal and Topical Administration Transdermal administration is used to apply the drug on the skin surface. The drug is absorbed and transported by blood to receptors, which may be remote from the part of the skin where the transdermal patch is. The flrst pass metabohsm is circumvented. Topical administration is used to apply the drug for local effects. The typical areas for topical application are the skin, eyes, throat, nose, and vagina. 

Opioids are generally well absorbed enterally (Reisine and Pasternak 1996). However, blood levels of morphine only reach half of those reached by injection. The more lipid soluble opioids are absorbed through the nasal mucosa or transdermally (e.g., fentanyl). Transdermal administration is much slower and more prolonged, avoiding the fluctuating levels produced by injection. 

Rose JE, Jarvik ME, Rose KD (1984) Transdermal administration of nicotine. Drug Alcohol Depend 13 209-213... 

Nagamanl M, Kelver ME, Smith ER. Treatment of menopausal hot flashes with transdermal administration of clonidine. Am I Obstet Gynecol 1987 156 561-565. 

Pharmacokinetics Absorbed slowly after transdermal administration. Protein binding 5%. Metabolized in the liver. Excreted primarily in urine. Half-life 4 hr. 

Figure 7 Requirements for an ideal substance for transdermal administration.

Typical patches of estradiol contain 50 micrograms, but there are important differences between the wanted and unwanted effects of the available products, because of the ways in which they are formulated. The wash-out period of estradiol after transdermal administration is about 6 weeks. Transdermal estrogens can also be supplemented periodically by an oral progestogen (222). New topical formulations of estrogens continue to be studied and... 

All the systemic effects of estrogens can occur with transdermal administration, subject to some modification as a result of the liver being bypassed (228). 

Cevc, G., and G. Blume. 2001. New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers. Transfersomes. Biochim Biophys Acta 1514 191. 

Meyer, B.R., et al. 1988. Successful transdermal administration of therapeutic doses of a polypeptide to normal human volunteers. Clin Pharmacol Ther 44 607. 

Nakamura, K., et al. 2003. Transdermal administration of salmon calcitonin by pulse depolarization-iontophoresis in rats. Int J Pharm 218 93. 

Physical therapists may encounter the use of local anesthetics in several patient situations because of their various clinical applications. For example, therapists may be directly involved in the topical or transdermal administration of local anesthetics. As discussed earlier, repeated topical application of local anesthetics may help produce long-term improvements in motor function in patients with skeletal muscle hypertonicity, so therapists may want to consider incorporating topical anesthetics into the treatment of certain patients with CNS dysfunction. Therapists may also administer local anesthetics transdermally, using the techniques of iontophoresis and phonophoresis. Agents such as lido-caine can be administered through this method for the treatment of acute inflammation in bursitis, tendinitis, and so on. 

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. 

Toxicology of the methylated derivatives has not been studied extensively. The LD50 for oral administration of dimethyl (3-cyclodextrin is >300mg/Kg and >200mg/Kg for intravenous administration in mice.65 Methylated derivatives interact with cellular membranes, extracting cholesterol and disrupting the membranes. This has limited interest in the derivatives for intravenous delivery of pharmaceuticals, but there has been some interest in use of methylated derivatives to enhance transdermal administration of drugs.66... 

The route of administration influences the likelihood of an antibody response independent of the mechanism of induction. The probability of an immune response is the highest with subcutaneous administration, less probable after intramuscular administration and intravenous administration is the least immunogenic route. There are no studies comparing parenteral and nonparenteral routes of administration. Flowever, as both mucosal tissues and the skin are immune competent organs designed to keep invaders out of the body, intranasal, pulmonary, and transdermal administration of therapeutic proteins may increase the risk of an immune response as compared to parenteral routes. 

Degim, I., Acrturk, F., Erdogan, D., and Lortlar, N. 2003. Transdermal administration of bromocriptine. Biol. Pharm. Bull., 26,501. 

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