Optimization of polylactic-co-glycolic acid nanoparticles containing itraconazole using 23 factorial design

This study investigated the utility of a 23 factorial design and optimization process for polylactic-co-glycolic acid (PLGA) nanoparticles containing itraconazole with 5 replicates at the center of the design. Nanoparticles were prepared by solvent displacement technique with PLGAX1 (10, 100 mg/mL), benzyl benzoateX2 (5, 20 μg/mL), and itraconazoleX3 (200, 1800 μg/mL). Particle size (Y1), the amount of itraconazole entrapped in the nanoparticles (Y2), and encapsulation efficiency (Y3) were used as responses. A validated statistical model having significant coefficient figures (P<.001) for the particle size (Y1), the amount of itraconazole entrapped in the nanoparticles (Y2), and encapsulation efficiency (Y3) as function of the PLGA (X1), benzyl benzoate (X2), and itraconazole (X3) were developed: Y1=373.75+66.54X1+52.09X2+105.06X3−4.73X1X2+46.30X1X3; Y2=472.93+73.45X1+ 169.06X2+333.03X3+62.40X1X3+141.49X2X3; Y3= 57.36+6.53X1+15.52X2−12.59X3+1.01X1X3+ 1.73X2X3.X1,X2, andX3 had a significant effect (P<.001) onY1,Y2, andY3. The particle size, the amount of itraconazole entrapped in the nanoparticles, and the encapsulation efficiency of the 4 formulas were in agreement with the predictions obtained from the models (P<.05). An overlay plot for the 3 responses shows the boundary in whichY1 shows the boundary in which a number of combinations of concentration of PLGA, benzyl benzoate, and itraconazole will result in a satisfactory process. Using the desirability approach with the same constraints, the solution composition having the highest overall desirability (D=0.769) was 10 mg/mL of PLGA, 16.94 μg/mL of benzyl benzoate, and 1001.01 μg/mL of itraconazole. This approach allowed the selection of the optimum formulation ingredients for PLGA nanoparticles containing itraconazole of 500 μg/mL

Controlled Release of Oral Tetrahydrocurcumin from a Novel Self-Emulsifying Floating Drug Delivery System (SEFDDS)

The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9–32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations