title: Design and mechanism of on-off pulsed drug release using nonenteric polymeric systems via pH modulation.
abstract: The aim was to design a pH-sensitive pulsatile drug delivery system that allows for an on-off pulsed release of a drug using polyacrylic acid (PAA) blended with ethyl cellulose (EC) in different ratios. PAA, a polyelectrolyte polymer, exhibits a highly coiled conformation at low pH but a highly extended structure at high pH. Fumaric acid, which is an internal acidifying agent, was incorporated into the hydroxypropyl methylcellulose-based core tablets to create an acidic microenvironmental pH (pH(M)). The concentration of fumaric acid inside the core tablet and the ratio of PAA/EC in the coating layer were very crucial in modulating drug release behaviors. When the fumaric acid was retained in the core tablet, it gave a more acidic pH(M), so that the PAA was kept in a highly coiled state in the coated film, which hindered drug release ("off" release pattern). Interestingly, the release profiles of the drug and fumaric acid from coated tablets showed the on-off pulsed pattern upon dissolution. Imaging analyses using scanning electron microscopy, near-infrared imaging, confocal laser scanning microscopy, and Fourier transform infrared spectroscopy confirmed this on-off release behavior of the drug and fumaric acid from coated tablets.
authors.affiliation: Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Phuong Ha-Lien
authors.initials: PH
authors.lastname: Tran
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Choe
authors.forename: Thao Truong-Dinh
authors.initials: TT
authors.lastname: Tran
authors.forename: Young Min
authors.initials: YM
authors.lastname: Park
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005079:Excipients; D005650:Fumarates / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D018613:Microscopy, Confocal; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D013607:Tablets; D013726:Terbutaline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000180:Acrylic Resins; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D005650:Fumarates; D011108:Polymers; D013607:Tablets; D065347:Hypromellose Derivatives; C006903:carbopol 940; C013517:ethyl cellulose; C032005:fumaric acid; D002482:Cellulose; D008747:Methylcellulose; D013726:Terbutaline; C047766:bambuterol