Abstract
The aim of current study was to optimize the effect of process and formulation parameters and to develop nanoparticulate drug delivery system to achieve sustained release of Prednisolone (PS) from a biodegradable polymer; PLGA. PS loaded PLGA nanoparticles were fabricated using nanoprecipitation technique with poloxamer 188 as a stabilizer. Quality by design approach was implemented to optimize effect of parameters and generate the design space using selected I-Optimal RSM design for design of experimentation (DoE) based on the risk assessment, an element of QbD approach. The effect of critical material; PLGA: Poloxamer 188 ratio and process parameter; stirring speed were linked to CQAs; particle size and % entrapment efficiency. The prepared PS loaded PLGA nanoparticles were characterized for particle size, polydispersity index (PDI) (Malvern Zetasizer ZS 90), entrapment efficiency, in-vitro diffusion study, DSC, XRD, SEM. Acceptance criteria for CQAs were considered as particle size in the range of 150-350 nm and entrapment efficiency in the range of 55-78.14 % w/w, which gave the design space with combination of selected critical parameters assuring robust formulation with desired Quality Target Product Profile (QTPP). PS loaded PLGA nanoparticles were spherical in shape, has narrow PDI. In-vitro diffusion study showed initial burst effect due to surface embedded drug and further gives sustained drug release which might be due to PLGA nanoparticles matrix system. Validation of model performed by comparing experimental values with predicted value of representative formulation within design space, confirming validity of generated mathematical model. Optimized formulations of PS loaded PLGA nanoparticles showed 78.14±0.20 % entrapment efficiency, particle size 173.7 nm with 0.103 PDI within design space which demonstrated effective drug delivery providing sustained drug release for a period of more than 4 weeks. Hence it can be concluded that QbD approach can be successfully implemented to optimize the effect of process and formulation parameters resulting the effective targeting of drug for long term therapy with PLGA as biodegradable polymer.
