title: Mechanisms of diphylline release from dual-solute loaded poly(vinyl alcohol) matrices.
abstract: The release kinetics of the model hydrophilic drug, diphylline (DPL), from physically crosslinked poly(vinyl alcohol) (PVA) matrices, is studied in relation to the drug load and the presence of a second solute incorporated in the matrix. The second solute, a gadolinium (III) complex (Gd-DTPA), is a commonly used MRI contrast agent. The water uptake kinetics by the glassy PVA matrix was found to deviate from t(1/2) law and to occur on time scales comparable to those of diphylline release. The corresponding rate of diphylline release was found to be substantially stabilized as compared to a purely diffusion-controlled release process, in line with theoretical predictions under conditions of relaxation-controlled water uptake kinetics. The release rate of DPL was found (i) to increase with increasing DPL load and (ii) for a particular DPL load, to increase in the presence of Gd-DTPA, incorporated in the matrix. The results were interpreted on the basis of the diphylline-induced plasticization of the polymer (evidenced by the depression of Tg) and of the excess hydration of the matrix at high solute loads. The latter effect was found to be additive in the case of dual-solute loaded matrices.
authors.affiliation: Dept. of Physical Chemistry, Institute of Advanced Materials, Physicochemical Processes, Nanotechnology and Microsystems, National Center for Scientific Research "Demokritos", 15310 Ag. Paraskevi, Athens, Greece.
authors.forename: Albana
authors.initials: A
authors.lastname: Hasimi
authors.forename: Kyriaki G
authors.initials: KG
authors.lastname: Papadokostaki
authors.forename: Merope
authors.initials: M
authors.lastname: Sanopoulou
mesh_terms: D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry*; D004400:Dyphylline / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D007700:Kinetics; D008970:Molecular Weight; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D014867:Water; D004400:Dyphylline; D011142:Polyvinyl Alcohol; D005682:Gadolinium
keywords: Diphylline; Gd-DTPA; PVA; Release kinetics; Release rate; Water sorption kinetics