Development of sustained-release microspheres for the delivery of SAR 1118, an LFA-1 antagonist intended for the treatment of vascular complications of the eye.

The objective of this study was to design 1, 3, and 6 month sustained-release poly (lactide-co-glycolide) (PLGA) microspheres of SAR 1118, a lymphocyte function-associated antigen-1 antagonist, using Design of Experiments. A full-factorial design was used to identify the polymers suitable for degradation in 1, 3, and 6 months and the Box-Behnken design was used to study the influence of the polymer type, polymer concentration, and drug to polymer ratio on drug loading, burst release, and particle size. From the full-factorial design, PLGA (50:50), PLGA (75:25), and PLGA (85:15) with an inherent viscosity of 0.3-0.5 dL/g were identified as polymers suitable for degradation in 1, 3, and 6 months, respectively. From the Box-Behnken design, the optimized polymer concentration (12% w/v) and drug to polymer ratio (0.15) were identified and used to prepare the SAR 1118-encapsulated microspheres with the above 3 polymers and evaluated for drug loading, burst release, and sustained drug release. The burst release in these 3 batches was less than 20% and the drug loading ranged from 15%-18%. More than 90% of SAR 1118 release from PLGA (50:50), PLGA (75:25), and PLGA (85:15) microspheres occurred in 1, 3, and 6 months, respectively. Thus, the in vitro cumulative release data are remarkably close to the predicted values. The results demonstrated the potential of the Design of Experiments in designing the SAR 1118 microspheres with a high loading efficiency, low burst release, and sustained release for a desired duration.