SPL Set ID: c41eb913-5e47-46c4-9d96-9a67f8380919

Clonidine transdermal system USP provides continuous systemic delivery of clonidine USP for 7 days at an approximately constant rate. Clonidine USP 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: C 9 H 9 Cl 2 N 3 M.W. 230.10 Chemical Structure System Structure and Components Clonidine transdermal system USP is a multi-layered film, 0.2 mm thick, containing clonidine USP as the active agent. The system areas are 4.33 cm 2 (clonidine USP 0.1 mg per day), 8.67 cm 2 (clonidine USP 0.2 mg per day) and 13 cm 2 (clonidine USP 0.3 mg per day) and the amount of drug released is directly proportional to the area (see Release Rate Concept ). The composition per unit area is the same for all three doses. The inactive ingredients are: aluminum, colloidal silicon dioxide, ethylene vinyl acetate copolymer, light mineral oil, microporous polypropylene membrane, pigmented polyethylene polyester film, polyisobutylene and silicon coated polyester film. Proceeding from the visible surface towards the surface attached to the skin, there are four consecutive layers: 1) a backing layer of polyester film; 2) a drug reservoir; 3) a microporous polypropylene membrane that controls the rate of delivery of clonidine USP from the system to the skin surface; 4) an adhesive formulation. Prior to use, a protective slit release liner of silicone coated polyester film that covers the adhesive layer is removed. Cross Section of the System: Figure Release Rate Concept Clonidine transdermal system USP is programmed to release clonidine USP at an approximately constant rate for 7 days. The energy for drug release is derived from the concentration gradient existing between a saturated solution of drug in the system and the much lower concentration prevailing in the skin. Clonidine USP flows in the direction of the lower concentration at a constant rate, limited by the rate-controlling membrane, so long as a saturated solution is maintained in the drug reservoir. Following system application to intact skin, clonidine USP in the adhesive layer saturates the skin site below the system. Clonidine USP from the drug reservoir then begins to flow through the rate-controlling membrane and the adhesive layer of the system into the systemic circulation via the capillaries beneath the skin. Therapeutic plasma clonidine USP levels are achieved 2 to 3 days after initial application of clonidine transdermal system USP. The 4.33, 8.67 and 13 cm 2 systems deliver 0.1, 0.2, and 0.3 mg of clonidine USP 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 USP. If the clonidine transdermal system USP is removed and not replaced with a new system, therapeutic plasma clonidine USP 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.