Water-activated, pH-controlled patch in transdermal administration of timolol: I. Preclinical tests

• Published in: European journal of pharmaceutical sciences Vol. 11; no. 1; pp. 19 - 24
• Main Authors: Sutinen, Riitta, Paronen, Petteri, Urtti, Arto
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.07.2000; Elsevier
• Subjects: Administration, Cutaneous; Adrenergic beta-Antagonists - pharmacokinetics; Biological and medical sciences; Controlled release; Drug delivery; Eye; General pharmacology; Humans; Hydrogen-Ion Concentration; Medical sciences; Models, Biological; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Silicone; Silicone Elastomers - pharmacokinetics; Skin Absorption - physiology; Skin permeation; Timolol; Timolol - pharmacokinetics; Transdermal; Drug delivery; Transdermal; Timolol; Controlled release; Silicone; Skin permeation; Antiglaucomatous agent; Human; Transdermal system; Pharmaceutical technology; Controlled release form; Permeation; Prediction; Preclinical trial; In vitro; Percutaneous route; Simulation; Dosage form; pH; Active ingredient; Skin; Pharmacokinetics; Patch; Siloxane polymer; Release; Beta blocking agent
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(00)00082-8

Previously, transdermal patches with internal pH-controlled release were described. The aim of this study was to test the suitability of the patch design in transdermal delivery and, further, to select such transdermal patch formulations to a clinical study with timolol. In vitro release of timolol from the patches was determined as well as timolol permeation across the human cadaver skin. The effect of the skin on drug release were evaluated in vitro. In vitro data and pharmacokinetic parameters from the literature were used to construct a pharmacokinetic model for the prediction of in vivo performance of the devices. With water-activated, pH-controlled silicone reservoir devices, both the rate of drug release and the duration of constant release were controlled. The rate of timolol release was decreased when the devices were placed on human cadaver skin, and thus, the skin partly controls the rate and extent of timolol delivery to the systemic circulation in vivo. On the basis of in vitro data and kinetic simulations, devices of 10-cm 2 volume releasing timolol in vitro at the rates of 119 and 10 μg h −1 cm −2 were selected for human tests.