Water-activated, pH-controlled patch in transdermal administration of timolol: II. Drug absorption and skin irritation

• Published in: European journal of pharmaceutical sciences Vol. 11; no. 1; pp. 25 - 31
• Main Authors: Sutinen, Riitta, Paronen, Petteri, Saano, Veijo, Urtti, Arto
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.07.2000; Elsevier
• Subjects: Administration, Cutaneous; Adrenergic beta-Antagonists - adverse effects; Adrenergic beta-Antagonists - blood; Adult; Biological and medical sciences; Drug absorption; Exanthema - chemically induced; Eye; Female; General pharmacology; Humans; Hydrogen-Ion Concentration; Male; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Silicone; Silicone Elastomers - pharmacokinetics; Skin Absorption - physiology; Skin irritation; Stella ® simulations; Timolol; Timolol - adverse effects; Timolol - blood; Transdermal patch; Skin irritation; Transdermal patch; Stella ® simulations; Timolol; Silicone; Drug absorption; Antiglaucomatous agent; Human; Transdermal system; Pharmaceutical technology; Toxicity; Normal; Blood plasma; Percutaneous route; Absorption; Simulation; Dosage form; Skin; Pharmacokinetics; Patch; Beta blocking agent; Irritation
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(00)00083-X

The feasibility of the water-activated, pH-controlled silicone reservoir devices for transdermal administration was investigated using timolol maleate as a model drug. Timolol patches were applied to the arm of 12 volunteers for 81 h, two patches per subject. Timolol absorption from patches was compared to that from a peroral timolol tablet formulation (Blocanol ® 10 mg). Furthermore, in vivo plasma levels of timolol were compared with those predicted by kinetic simulations. Skin irritation induced by timolol patches was assessed by visual scoring and color reflectance measurements. With water-activated, pH-controlled patches both steady-state concentrations of timolol in plasma and its duration could be controlled. However, a considerable, inter-individual variability in the transdermal absorption of timolol was observed. This is due to the high fractional skin control in timolol delivery. Timolol patches were well tolerated by subjects. Skin irritation induced by the combination of timolol with long-term occlusion was mild, and after removal of the patches, skin changes were practically reversed in 24 h. Simulation model was useful in prediction of timolol levels in plasma after transdermal administration.