|
|
|
|
|
|
|
more constant than those of oral medication [14]. In addition to seven day efficacy after each transdermal application versus 12 or 8 hour efficacy with use of tablets, Catapres TTS provides for a reduced side effect profile and controls hypertension with a lower daily dosage of clonidine. Drowsiness and dry mouth, the two important side effects of clonidine are reduced by transdermal therapy [15,16]. Catapres TTS sales have been increasing continuously since its introduction in 1985, with U.S. sales reaching $47 million in 1993 despite the fact that over 15% of the population using the patch develops skin sensitization. |
|
|
|
|
|
|
|
|
B. Reduction of Side Effect Profile |
|
|
|
|
|
|
|
|
As mentioned above, Catapres TTS was able to reduce side effects by lowering the daily dose of clonidine and by the elimination of peaking concentrations. Reduction of side effects can also be accomplished for drugs that are substantially metabolized during the first pass through the liver. Estradiol is a physiological hormone secreted by the ovaries and it is used therapeutically for systemic estrogen replacement for postmenopausal women and prevention of osteoporosis. A once-daily oral bolus of estradiol has been likened to hitting the liver with a hammer every 24 hours, so marked are the elevations in some hepatically derived proteins that result. These elevations have been postulated to cause certain serious side effects of exogenous estrogens, including hypertension, hyperlipidemia, and hypercoagulability [17]. Elimination of the rapid first-pass metabolism of estradiol to estrone and continuous control of the delivery of estradiol to the systemic circulation would minimize these problems. The Estraderm transdermal system addresses these issues. The system is comprised of four layers. Proceeding from the visible surface toward the surface attached to the skin, these layers are: (a) a transparent polyester film; (b) a drug reservoir of estradiol USP and alcohol USP gelled with hydroxypropyl cellulose; (c) an ethylene-vinyl acetate copolymer membrane; and (4) an adhesive formulation of light mineral oil and polyisobutylene. A protective liner (e) of siliconized polyethylene terephthalate film is attached to the adhesive surface and must be removed before the system can be used [18]. |
|
|
|
|
|
|
|
|
Since the skin does not significantly metabolize estradiol delivered from Estraderm, only 5% of the amount of drug used in oral dosing was required to achieve the same blood plasma levels. Clinical studies in postmenopausal women showed that Estraderm delivered therapeutically effective, physiologic levels of estradiol without the unusually high levels of estrone associated with hepatic metabolism of estradiol [19,20]. |
|
|
|
|
|
|
|
|
II. Routes of Administration |
|
|
|
|
|
|
|
|
As mentioned earlier, novel routes or forms of drug delivery may offer several advantages over conventional dosage forms. However, the desire to increase |
|
|
|
|
|