Optimization of spray-dried diclofenac sodium-loaded microspheres by screening design

Abstract

ABSTRACTThe aim of the present study was to investigate the effect of formulation and operating parameters of the laboratory spray dryer on polymeric microspheres intended to be used for sustaining drug delivery of diclofenac sodium (DS). Four operating and four formulation parameters were investigated by Plackett–Burman design to enhance the encapsulation efficiency (EE). The independent variables were air inlet temperature, aspirator, feed flow rate, spray nozzle diameter, amount of drug, amount of polymers, and volume of organic solvent. The resultant microspheres were characterized for their EE. The microspheres having high EE were further characterized for particle size, morphology, and in vitro drug release. Interaction between the drug and the polymer were investigated by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry (XRPD). The Pareto chart showed that amount of Eudragit® RS100, amount of ethylcellulose, and aspirator were identified as significant factors. The microspheres showed high EE (47.55 ± 0.006% to 67.99 ± 0.007%). The microspheres were found to be discrete, spherical with smooth surface. The FTIR analysis confirmed the compatibility of DS with the polymers without interaction. The XRPD revealed the dispersion of drug within microspheres formulation. The in vitro drug release from these DS-loaded microspheres showed sustained release of DS over a period of 12 h and followed the Korsmeyer–Peppas model [R2 = 0.9920 (Run 1) and 0.9957 (Run 13)] with a value of the slope (n) ≤ 0.43. This n value, however, appears to indicate that Fickian release is the dominant mechanism of drug release with these formulations.