A novel microsphere-gel formulation was investigated aiming to extend precorneal residence times for ocular drugs. Poly(adipic anhydride) was used for microencapsulation of timolol maleate. A nonaqueous method for the microsphere preparation was required due to the hydrolytical sensitivity of the polymer. Microspheres were prepared with an average diameter of 40 mu m. The polymer and the microspheres were characterized before and during degradation using size exclusion chromatography (SEC), differential scanning calorimetry (DSC), x-ray diffraction, infrared spectroscopy (IR), and scanning electron microscopy (SEM). The microspheres had a smooth external surface and a hollow center surrounded by a dense outer shell. Degradation of the microspheres resulted in a constant release of adipic acid, the degradation product, indicating a surface-eroding degradation mechanism. The release of the incorporated substance, timolol maleate, was controlled by the surface erosion of the polymer. The drug release rate profile appeared to be suitable for ocular drug delivery. The incorporation of the microspheres into a gel resulted in an extended release of timolol maleate. This microsphere-gel formulation is expected to result in a higher bio availability of drug to the eye than standard eye drops.