QBD Approach for Design and Characterization of Pramlintide Microspheres for Controlled Drug Release

Purpose The research was centered on the optimization of the microsphere formulation through a systematic quality-by-design (QBD) methodology, as well as the assessment of their performance in vitro and in vivo. Methods The procedure of fabricating microspheres containing pramlintide acetate involved the utilization of a solvent extraction and evaporation technique. The study utilized a Box-Behnken design to systematically optimize the critical process parameters (CPPs) and critical material attribute (CMA) of the microspheres. The evaluation of the microspheres included the assessment of particle size distribution, encapsulation efficiency, in vitro drug dissolution, and in vivo drug release. Results The study found that lowering the in vitro drug release rate was caused by increasing the intrinsic viscosity of the PLGA polymer. Additionally, higher homogenization speeds resulted in smaller particle sizes, leading to improved dissolution rates. An optimized microsphere formulation was created based on the results that were found to be best. This optimized formulation demonstrated controlled in vitro and in vivo drug release, reduced burst release, and efficient entrapment efficiency. Conclusion The present study effectively utilized a quality-by-design methodology in order to formulate controlled-release microspheres including pramlintide acetate. Through the methodical optimization of crucial process parameters and material properties, a state of optimal formulation was attained. This optimized formulation exhibited a linear and controlled release of the drug over a duration of 4 weeks, as evidenced by an in vivo pharmacokinetic investigation. Graphical Abstract