Clonidine Transdermal System is a transdermal system (patch) providing continuous systemic delivery of clonidine for 7 days at an approximately constant rate. Clonidine is a centrally acting alpha-agonist hypotensive agent. It is an imidazoline derivative with the chemical name 2, 6-dichloro-N-2-imidazolidinylidenebenzenamine and has the following chemical structure: 

System Structure and Components: Clonidine Transdermal System is a multi-laminate patch, 0.3 mm thick, containing clonidine as the active agent. The patch surface areas are 10.8 cm2 (Clonidine Transdermal System 0.1 mg/day), 21.6 cm2 (Clonidine Transdermal System 0.2 mg/day), and 32.4 cm2 (Clonidine Transdermal System 0.3 mg/day). The composition per unit area is the same for all three doses. 

Proceeding from the outer printed backing layer towards the surface applied to the skin, the system comprises: 1) a backing layer of polyethylene/aluminum/polyester film; 2) a drug reservoir layer of clonidine, isopropyl palmitate, and amine-compatible silicone adhesive; 3) an ethylene vinyl acetate (EVA) membrane that controls the rate of clonidine delivery from the system to the skin; 4) an amine-compatible silicone adhesive layer (ADHESIVE LAYER B); 5) an acrylate adhesive layer (ADHESIVE LAYER C) that attaches to the skin; and 6) a protective release liner of siliconized polyester that is removed prior to use. 

Cross-sectional view of the Clonidine Transdermal System. 

Not to scale. 

Release Rate Concept: Clonidine Transdermal System is designed to deliver clonidine through the skin at an approximately constant rate for 7 days. Saturated clonidine in the reservoir layer provides a concentration gradient between the system and the skin. Clonidine diffuses from the higher concentration in the system to the lower concentration in the skin. The rate of delivery from the system is primarily controlled by passage of clonidine through the EVA membrane. 

When a patch is applied to the skin (after removal of the protective release liner), clonidine dissolved in adhesive layers B & C is delivered to the skin. The EVA membrane then becomes the principal factor controlling clonidine delivery from the system by regulating clonidine release from the reservoir. A constant clonidine driving force is maintained by the drug reservoir layer, which contains a uniform dispersion of clonidine crystals. Clonidine is delivered through the skin and into the systemic circulation via the capillaries beneath the skin. Therapeutic plasma clonidine levels are achieved 2 to 3 days after initial application of Clonidine Transdermal System to the skin. 

The 10.8, 21.6, and 32.4 cm2 systems deliver 0.1, 0 2, and 0.3 mg of clonidine per day, respectively. To ensure constant release of drug for 7 days, the total drug content of the system is higher than the total amount of drug delivered. Application of a new system to a fresh skin site at weekly intervals continuously maintains therapeutic plasma concentrations of clonidine. If the Clonidine Transdermal System is removed and not replaced with a new system, therapeutic plasma clonidine levels will persist for about 8 hours and then decline slowly over several days. Over this time period, blood pressure returns gradually to pretreatment levels.