title: Viscosity of polymer solution phase and other factors controlling the dissolution of theophylline microspheres prepared by the emulsion solvent evaporation method.
abstract: The objectives of this investigation are to evaluate the effect of the viscosity of polymer solution phase on microsphere properties, especially the drug release characteristics since no studies on this formulation variable have been reported. Also, since it is known that polymer molecular weight affects both the viscosity of the polymer solution and the release properties of microspheres, the interaction of these factors was studied. Microspheres with 33% theoretical drug loading of anhydrous theophylline core material were prepared by the emulsion solvent evaporation method. Two cellulose acetate butyrate polymers, (CAB381-2, CAB381-20), chemically similar but having different molecular weights, were used to prepare different polymer solutions having different apparent viscosities in acetone. A Brookfield viscometer was used to evaluate the viscosities of polymer solutions. Dissolution rates of microspheres prepared from the polymer solutions were inversely related to the initial polymer solution viscosities for both CAB381-2 and CAB381-20. The times for the release of 30 and 50% of the drug from the microspheres have a linear relationship with initial polymer solution viscosity. Initial release was significantly decreased with increasing polymer solution viscosity. Unlike CAB381-2 microspheres which follow Higuchi spherical matrix release kinetics, microspheres prepared from the higher molecular weight polymer (CAB381-20) showed extended release dissolution profiles with near zero order kinetics. It is evident that both the polymer solution viscosity and the molecular weight have an effect on the drug release from microspheres. These results suggest that release rates of matrix microspheres could be predictably optimized by adjusting the viscosity of polymer solutions.
authors.affiliation: University of Georgia, Athens, Georgia 30602, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Obeidat
authors.forename: J C
authors.initials: JC
authors.lastname: Price
mesh_terms: D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004655:Emulsions; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011108:Polymers; D012997:Solvents; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D011108:Polymers; D012997:Solvents; D013806:Theophylline