Preparation and Preliminary Scale-Up Validation of Polycaprolactone Microspheres for Facial Filling Based on Intelligent Algorithm Optimization

To simultaneously achieve the goals of minimizing particle size within the 25–40 μm range and obtaining the narrowest possible particle size distribution (lowest Span value), the formulations of polycaprolactone microspheres (PCL-MS) were screened. After applying single-factor studies and the Box-Behnken design method, formulation optimization was conducted via the Nondominated Sorting Genetic Algorithm-II. From the Pareto non-inferiority solution sets containing 30 formulations, the 12th and 21st formulations were selected for experimental verification, since they were the closest to the target. The scale of formulation 21 was magnified tenfold. The resulting PCL-MS exhibited no significant changes in particle size or Span value. Scanning electron microscopy revealed a smooth, rounded MS surface, and organic solvent residue testing met regulatory requirements. This fully demonstrated the applicability of the optimized formulation under scaled-up conditions, providing a formulation reference for industrial quality control of PCL-MS.