INFLUENCE OF FORMULATION METHODS ON THE INVITRO CONTROLLED RELEASE OF PROTEIN FROM POLY(ESTER) MICROSPHERES

Poly(DL-lactide/glycolide, 50:50) microspheres containing bovine serum albumin (BSA) were prepared with and without Carbopol(R) 951 (a potential adjuvant agent) by o/o, o/w and (w/o)/w emulsion methods. The protein loading of the microspheres reached 50-70% of the theoretical amount of protein put into the formulation medium. The microsphere particle size was approximately 500-mu-m, 25-100-mu-m, 10-20-mu-m using o/o, o/w, or (w/o)/w emulsion techniques, respectively. The release of BSA was dependent on the preparation method. The greatest burst of release was found for vacuum-dried microspheres formulated using the (w/o)/w method. This burst effect could be eliminated by lyophilizing the microspheres following their preparation. BSA was released at a higher initial rate from microspheres prepared by the o/w emulsion method that contained Carbopol(R) 951 than from microspheres not containing Carbopol(R) 951. Release studies also suggested that the release of BSA could be sustained for 54, 36, or 34 days for microspheres prepared by o/o, o/w, or (w/o)/w methods, respectively.