FORMULATION, DEVELOPMENT AND OPTIMIZATION OF MICROSPHERE CONTAINING CRISABOROLE BY DESIGN OF EXPERIMENT APPROACH

Abstract

ABSTRACT The present study was aimed at the formulation, development, and optimization of Crisaborole-loaded microspheres using a Design of Experiment (DoE) approach for potential topical drug delivery. Crisaborole is a topical phosphodiesterase-4 inhibitor used in the management of inflammatory skin conditions; however, its poor aqueous solubility presents a challenge for conventional formulation development. Preformulation studies were performed to evaluate the organoleptic properties, solubility, pH, melting behavior, UV absorption characteristics, calibration profile, and FTIR spectrum of Crisaborole. The drug exhibited a white to off-white crystalline powder appearance and was practically insoluble in water but showed better solubility in selected organic solvents. The maximum absorption wavelength was observed at 251 nm. A Box–Behnken design was employed to optimize three formulation variables, namely polymer concentration, surfactant concentration, and stirring time, using particle size and entrapment efficiency as the critical responses. The particle size of the prepared formulations ranged from 166.24 to 862.11 nm, while entrapment efficiency ranged from 67.08 to 95.87%. The linear model was found to be statistically significant for both responses, with p < 0.0001. The optimized formulation exhibited a predicted particle size of 184.778 nm and an experimental particle size of 204.6 nm, with a zeta potential of −21.4 mV. The predicted entrapment efficiency was 95.586%, whereas the experimentally obtained value was 93.43%, demonstrating good agreement between predicted and experimental values. SEM analysis confirmed the formation of nearly spherical microspheres with relatively smooth and intact surfaces. In-vitro drug release studies demonstrated sustained drug release up to 98.97% over 14 h. The release data showed the best fit with the Higuchi model (R² = 0.992), indicating predominantly diffusion-controlled drug release. Stability studies over 90 days under long-term and accelerated conditions showed only minor changes in formulation characteristics. Overall, the DoE approach successfully identified optimized formulation conditions and produced Crisaborole-loaded microspheres with satisfactory particle characteristics, high drug entrapment, sustained release, and acceptable stability, indicating their potential for topical drug delivery. Keywords: Crisaborole; Microspheres; Design of Experiment; Box–Behnken Design; Response Surface Methodology; Particle Size; Entrapment Efficiency; Zeta Potential; Sustained Drug Release; Topical Drug Delivery.