Transdermal products

No transdermal products have been marketed for use in the pediatric population. The development of transdermal products in pediatric doses could be very beneficial for children who are unable to tolerate oral medications. 

Variation of temperature is usually not an issue for solid oral dosage forms, since experiments are always conducted at body temperature (37°C). For dosage forms applied on the skin, this can be a further consideration e.g., drug-release testing of transdermal products is typically performed at the average temperature of body surface 32°C (5). 

In a case-control study 155 postmenopausal women who had had venous thromboembolism were compared with 381 matched controls (91). In all, 32 cases and 27 controls were current users of oral replacement therapy, whereas 30 cases and 93 controls were current users of transdermal products. After adjustment for potential confounding variables, the estimated risk ratio for venous thromboembolism in current users of the oral products compared with the transdermal users was 4.0 (1.9-8.3). This is strong evidence that the transdermal route was considerably safer. However, the conclusions of different studies continue to conflict with one another, no doubt in part because of variations in the formulations and patterns of use of the products. 

Ophthalmic, transmucosal, and transdermal products will be the most sensitive to the strength of binding. These routes of administration experience minimal dilution. However, this may not be a signiLcant concern because the drug typically can also be displaced from the CD cavity at the delivery site by competing lipophiles at the delivery site, such as triglycerides, cholesterol, bile salts, and other hydrophobic compounds, which are often in much higher concentrations (Thompson, 1997). 

In the case of the laboratory, what is its function relative to the transdermals manufactured under CGMP Generally the laboratory is where the various methods used to evaluate the attributes of a given transdermal or intermediate are developed, qualified, and validated. Many of these methods can often be adapted directly from the USP. If a special non-USP-derived method is required to evaluate a transdermal product, then the company is obligated to demonstrate and document that the method selected is valid. The validity of the method is determined by a thorough evaluation of the following parameters [3] ... 

The transdermal manufacturing process is typically validated after the equipment qualification steps have been successfully completed. A good process validation requires each of the preceding validation steps be done successfully. Given that they are successfully completed, the full-scale process for manufacturing the transdermal is run three consecutive times. All formal SOPs (production, laboratory, warehouse, etc.) that affect the transdermal product must therefore be effective and referenced throughout process-validation activities. 

TABLE 4.1 Compounds in Transdermal Products Marketed and to Be Marketed... 

Transdermal products with semisolid matrix design include Habitrol, Nitrodisc, Nitroglycerin Transdermal, and Prostep. For example, Habitrol consists of an impermeable backing laminate with a layer of adhesive and a nonwoven pad to which a nicotine solution is applied. Multiple layers of adhesive on a release liner are then laminated on the patch. The systems come in 10-, 20-, and 30-cm2 sizes corresponding to 7, 14, and 21 mg/day, respectively, delivered over 24 hours. 

Topical and transbuccal systems. In the current literature, unfortunately, transdermal products usually are labeled for systemic use only. It is the time to define transdermal products for topical (excluding dermatological) use to those delivered through the intact and healthy skin directly into the local tissues or deeper regions beneath the skin. Dozens of these transdermal systems have been launched for topical use, including analgesics for muscle aches, neuropathic pain, and arthritis and the treatments of breast cancer and erectile dysfunction.88... 

Jordan and King (1977) proposed modifying the challenge procedure to two consecutive 48-h patch periods. The modified Draize test has recently been selected as the test of choice for chemicals in natural rubber products by the FDA. Tests for the transdermal products are currently being evaluated by the FDA. 

Nitrate therapy may be used to terminate an acute anginal attack, to prevent effort- or stress-induced attacks, or for long-term prophylaxis, usually in combination with j3-blockers or calcium channel antagonists. Suhhngual, huccal, or spray nitroglycerin products are preferred for alleviation of anginal attacks because of rapid absorption (Table 11-1). Symptoms may be prevented by prophylactic oral or transdermal products (usually in combination with j3-blockers or calcirun channel antagonists), but development of tolerance may be problematic. 

There are several variants to this apparatus, which is based on a sample holder that oscillates up and down in the medium vessel. The sample holder may take the form of a disk, cylinder, or a spring on the end of a stainless steel or acrylic rod, or it may simply be the rod alone. The sample is attached to the outside of the sample holder either by virtue of being self-adhesive (e.g., transdermal delivery system) or is glued in place using a suitable adhesive. This apparatus may be used for transdermal products, coated drug delivery systems, or other suitable products (e.g., osmotic pump devices). It is prescribed for the drug-release testing of Psuedoephedrine hydrochloride extended-release tablets USP where the tablets are enclosed in a 5x5 cm of nylon, which is then attached to the rod. 

Pharmacia and Upjohn, Kalamazoo, MI) and Cri-none Gel (Wyeth-Ayerst). Mineral oil is frequently present in transdermal products such as Catapres-TTS (Boehringer Ingelheim) and Estraderm (Novartis Pharmaceuticals Corp). In addition, numerous ocular or topical ointments, such as TobraDex (Alcon Labs, Fort Worth, TX) and Nitro-Bid (Hoechst Marion Roussel, Kansas City, MO), use white petrolatum and mineral oil as a base. Short-chain triglycerides such as triacetin can be found in products such as Prepidil Gel (Pharmacia-Upjohn, Kalamazoo MI), a cervically administered prostaglandin. 

Release tests can be applied to rectal and transdermal products by adapting methods used for oral products, altering the receptor phase to mimic the medium in which the formulation resides in vivo. 

Only few transdermal products (e.g., steroidal hormone, caffeine, theophylline, fentanyl, scopolamine, nicotine, methylphenidate) have been tested or marketed for use in the pediatric population. The development of transdermal products in pediatric doses could be very beneficial for children who are unable to tolerate oral medications. The need for several sizes of patches to cover different doses needed by different subsets of the pediatric population and to avoid accidents with cutting adult patches can be a limitation. The younger, the better permeation. Hence a compromise between topical versus transdermal efficacy and safety should be sought. 

Tablets alone and in oral contraceptives. g Transdermal products.

To fully evaluate the equivalence of a transdermal product for an abbreviated new drug application to a reference-listed drug, skin irritation and sensitization should be assessed because the condition of the skin may affect the absorption of a drug from a transdermal system. More severe skin irritation may affect the efficacy or safety of the product. 

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