PREPARATION AND CHARACTERIZATION OF POLY(ADIPIC ANHYDRIDE) MICROSPHERES FOR OCULAR DRUG-DELIVERY

A novel microsphere-gel formulation was investigated aiming to extend precorneal residence times for ocular drugs. Poly(adipic anhydride) wa s used for microencapsulation of timolol maleate. A nonaqueous method for the microsphere preparation was required due to the hydrolytical s ensitivity of the polymer. Microspheres were prepared with an average diameter of 40 mu m. The polymer and the microspheres were characteriz ed before and during degradation using size exclusion chromatography ( SEC), differential scanning calorimetry (DSC), x-ray diffraction, infr ared spectroscopy (IR), and scanning electron microscopy (SEM). The mi crospheres had a smooth external surface and a hollow center surrounde d 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 incorpora ted 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 microsph ere-gel formulation is expected to result in a higher bio availability of drug to the eye than standard eye drops. (C) 1996 John Wiley & Son s, Inc.