QUALITY BY DESIGN APPROACH TO OPTIMIZATION OF TACROLIMUS LOADED PLGA NANOPARTICLES

The aim of the present study was to implement QbD approach to identify, evaluate and control critical process and formulation parameters and their impact on critical quality attributes (CQAs) and to establish design space with multifactorial combination which would provide high degree of assurance to achieve quality target product profile (QTPP). A risk assessment was performed with various process and formulation parameters to determine their impact on particle size and encapsulation efficiency (CQAs) of nanoparticles and further high risk parameters were optimized using I-Optimal design. Design space was generated by setting limits to CQAs as per acceptance criteria of Tacrolimus loaded PLGA (TC PLGA) nanoparticles. The optimized formulation from design space was further characterized by XRD, DSC, SEM, in-vitro dissolution study. The nanoparticles obtained were free flowing, spherical, smooth and uniform. In-vitro dissolution study showed ability of nanoparticles to sustain drug release for period of 4 weeks. In conclusion, it can be demonstrated that, QbD approach was successfully implemented for understanding of process and formulation parameters and further develop robust design space for TC PLGA nanoparticles to achieve sustained drug release from complex PLGA delivery system.