Optimization of Formulation Variables Affecting Spray-dried Oily Core Nanocapsules by Response Surface Methodology

The formulation variables required for the production of spray-dried oily core nanocapsules (NCs) with targeted size and drug payload were optimized using a Box-Behnken experimental design. These NCs were characterized for size, morphology, encapsulation efficiency (EE%) and drug release kinetics, crystallinity, and density, by dynamic light scattering, electron microscopy, ultraviolet spectrometry, powder X-ray diffraction, and density-gradient centrifugation, respectively. The size of the NCs ranged from 208.6 to 504.4 nm, with EE% from 64.7% to 94.6%. The amounts of oil and surfactant (Pluronic F127) significantly affected size. The amounts of polymer [polylactide (PLA)], oil, and surfactant significantly affected EE%. The optimum formulation parameters were set to be 300 mg of PLA, 0.56 mL of oil, and 239.57 mg of Pluronic F127, which corresponded to size of 284.1 nm and EE% of 95.7%. Morphological analysis and density-gradient centrifugation showed the existence of an oily core and spherical nanostructure with no detectable drug crystals. The NCs had longer sustained drug release than nanosphere control, with a good fit to the Ritger-Peppas model (R(2) > 0.930). Spray-dried oily core NCs were successfully produced, and the Box-Behnken design appears to be an effective tool to predict the size and encapsulation of NCs.