FORMULATION OF BCNU-LOADED MICROSPHERES - INFLUENCE OF DRUG STABILITYAND SOLUBILITY ON THE DESIGN OF THE MICROENCAPSULATION PROCEDURE

The design of a microencapsulation procedure for the preparation of bi odegradable BCNU-loaded microspheres used as intracerebral implants is the aim of this work. This approach will give sustained high local co ncentrations of the anti-tumour drug in the brain without the associat ed significant systemic toxicity. The microencapsulation technique use d is a solvent-evaporation process based on the formation of an oil-in -water emulsion. The stability of BCNU in methylene chloride saturated with water and its high value of partition coefficient between methyl ene chloride and water justifies the selection of this organic solvent as the dispersed phase in the methodology. A spectrophotometric metho d for the quantification of BCNU in mixtures containing PLAGA. is deve loped which allows the evaluation of drug photodecomposition. The volu me of methylene chloride and the concentration of PVA in the external aqueous phase are the two variables that induce the largest variations of the microsphere size. The two main process parameters leading to t he highest microencapsulation yield are the polymer concentration in t he organic phase and the volume of the external aqueous phase; whereas the pH of the external aqueous phase and the use of co-solvents in th e organic phase lead only to a small improvement in microsphere payloa d.