Design, Optimization, and Evaluation of Tofacitinib-Loaded Cubosomes by Box–Behnken Experimental Design

Abstract

Tofacitinib is a Janus kinase inhibitor used in the management of inflammatory and autoimmune disorders. However, its therapeutic performance may be limited by its physicochemical properties. The present study aimed to formulate and optimize tofacitinib-loaded cubosomes using glyceryl monooleate (GMO) and Poloxamer 407 to obtain a stable nanocarrier system. Tofacitinib was characterized by preformulation investigations, which included organoleptic assessment, solubility analysis, melting point determination, partition coefficient measurement, and UV spectrophotometric analysis. Fourier- transform infrared spectroscopy (FTIR) was used to evaluate drug-excipient compatibility. utilizing GMO as the lipid phase and Poloxamer 407 as the stabilizer, tofacitinib-loaded cubosomes were created utilizing the top-down technique. In order to optimize the formulation, the effects of GMO concentration, Poloxamer 407 concentration, and stirring time on particle size and entrapment efficiency were assessed using a Box-Behnken experimental design. Its was The evaluation parameters were Scanning electron microscopy (SEM), particle size, zeta potential, entrapment efficiency, and surface morphology. Preformulation studies confirm possibility for lipid-based formulation development. FTIR analysis revealed no significant interaction between the drug and excipients, indicating good compatibility. Statistical analysis demonstrated that formulation variables significantly impacted particle size and entrapment efficiency, and the developed model showed satisfactory prediction. The optimized formulation containing 5% GMO, 1% Poloxamer 407, and 45 min stirring time showed a particle size of 274.1 nm, entrapment efficiency of 86.37%, and zeta potential of −35.6 mV. SEM analysis confirmed the formation of predominantly spherical nanoparticles with nanoscale dimensions. Therefore, cubosomes represent a promising approach for the delivery of tofacitinib and warrant further investigation for pharmaceutical applications