Characterization of Ibuproxam Binary and Ternary Dispersions with Hydrophilic Carriers

Abstract

This work investigates the possibility of increasing the dissolution properties of ibuproxam (a poorly water‐soluble anti‐inflammatory drug) using hydrophilic carriers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), or urea, alone or in combination. Phase‐solubility studies showed that the carrier solubilizing power was in the order PEG > PVP > urea and evidenced a synergistic effect in drug solubility improvement when using carrier combinations. Binary and ternary systems, at 20/80 or 20/40/40 (w/w) drug/carrier(s) ratios, prepared by coevaporation of their ethanolic solutions or by cogrinding physical mixtures in a high‐energy vibrational micromill, were characterized by differential scanning calorimetry (DSC), hot stage microscopy (HSM), and scanning electron microscopy (SEM) analyses. The results of dissolution tests (USP paddle method), in terms of Dissolution Efficiency, indicated that ternary systems were up to 35% more effective than the corresponding binary preparations and coevaporated products were up to 45% more efficacious than the corresponding coground ones. The IBUX‐PEG‐PVP coevaporated was the best product, allowing a more than three‐times increase in Dissolution Efficiency with respect to drug alone; moreover, t_50% ( > 60 min for pure ibuproxam) was < 10 min, and 90% dissolution was achieved after 30 min, whereas only 40% was obtained after 60 min for pure drug. The best performance of this system was attributed to a joined effect of the strong amorphizing power of PVP (as demonstrated by solid state analyses) with the high solubilizing efficacy of PEG (as emerged from phase‐solubility studies). The drug dissolution rate from solid dispersions remained practically unchanged after one‐year storage at room temperature in closed containers.

Key Words:

• Ibuproxam
• Ternary solid dispersions
• Coevaporation
• Cogrinding
• Hydrophilic carriers
• Dissolution