Development and characterization of buoyant theophylline microspheres with near zero order release kinetics

Abstract

The objective of this study was to prepare floating theophylline microspheres with zero order release profiles for use as buoyant reservoirs with increased retention time in the stomach. The microspheres were prepared by a modified emulsion-solvent evaporation method using a polymer mixture of cellulose acetate butyrate and Eudragit RL 100 (1:1). The drug-polymer dispersions were pressurized under carbon dioxide gas which dissolved in the drug-polymer dispersions and formed bubbles upon the release of the pressure. Some of the bubbles were entrapped in the dispersed drug-polymer droplets and eventually formed internal cavities in the microspheres. The resulting microspheres were characterized for size distribution, morphology, density, drug-polymer content, buoyant capacity and drug release behaviour. The microspheres were spherical with relatively smooth surfaces with round hollow cavities. The microspheres and low densities (less than 1 g/cm³) and remained floating for more than 24 h in pH 1.2 and 7.5 buffers. The dissolution profiles of the floating theophylline microspheres showed near zero order kinetics and sustained release in both pH 1.2 and 7.5 buffers. Modified microspheres processed with the addition of 2% w/v polysorbate 80 to the internal phase had smaller sizes, lower densities and faster drug release compared with those without the addition of the surfactant.

Key Words:

• Buoyant microspheres
• theophylline
• cellulose acetate butyrate
• Eudragit RL 100
• zero order release