title: Interpolymer Complexation Between Polyox and Carbopol, and Its Effect on Drug Release From Matrix Tablets.
abstract: Interaction between Polyox N12K and Carbopol 907 was pH dependent. A hydrogen bond-induced complexation began between pH 5.0 and 6.0 in an aqueous medium, and the interpolymer complex started to precipitate when the pH fell to 4.0. This complex was amorphous with a glass transition temperature of 3.17°C. The molar ratio between ethylene oxide and acrylic acid units in the complex was 1.3:1. About 46% of the COOH groups in Carbopol 907 were H bonded to ether oxygen in Polyox. Theophylline release from tablets containing both polymers was a function of dissolution media pH, due to the pH-dependent interactions. In 0.01 N HCl, an insoluble tablet matrix formed in situ. 93% drug was released over 27 h via Fickian diffusion. In acetate buffer pH 4.0, the insoluble tablet matrix formed in situ disintegrated into tiny gel particles. Gel erosion controlled drug release at pH 4.0. These 2 polymers were unable to complex in a phosphate buffer pH 6.8. Therefore, the tablet matrix dissolved, and drug release followed the anomalous transport mechanism at pH 6.8. The release profiles in an acetate buffer pH 4.0 and phosphate buffer pH 6.8 were statistically same, and a sustained release over 12 h was achieved.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas 78712. Electronic address: feng.zhang@austin.utexas.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California 94040.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lubach
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas 78712.
authors.forename: Watson
authors.initials: W
authors.lastname: Na
authors.affiliation: McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E. Dean Keeton Street, Austin, Texas 78712.
authors.forename: Samad
authors.initials: S
authors.lastname: Momin
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004347:Drug Interactions; D065546:Drug Liberation; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C000624961:Polyox N12K; D013607:Tablets; D011092:Polyethylene Glycols; C006903:carbopol 940; D013806:Theophylline
keywords: Fickian diffusion; anomalous transport mechanism; interpolymer complex; poly(acrylic acid); poly(ethylene oxide); sustained release