Synthesis, Characterization, and Stability Optimization of Ibuprofen Cocrystals eEploying Various Hydrophilic Polymers.

ABSTRACT

BACKGROUND: Cocrystals are an efficient way for the delivery of low soluble drugs but when dissolved they rapidly disproportionate. To formulate the cocrystals in tablets, cocrystals must be stabilized. In this study ibuprofen-nicotinamide (IBU-NIC) cocrystals were synthesized initially by slow solvent evaporation and for bulk production by fast solvent evaporation techniques. METHOD: The cocrystals were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectrophotometer (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The ibuprofen cocrystals showed greater solubility compared to the parent drug. RESULT: Intrinsic dissolution data was utilized for efficacious screening of tablet formulations. Using hydrophilic polymers at a ratio of 61 (polymer to IBU-NIC cocrystal ratio), hydroxypropyl methylcellulose (F1), polyvinylpyrrolidone (PVP) K-30 (F2) and PVP K-90 (F3), three tablet formulations were prepared that stabilized cocrystals during dissolution. The drug release profiles after 60 minutes from formulations F1 (92.30), F2 (98.54), F3 (99.88) were all higher compared to the marketed brand BRUFEN® F, (79.61%) in a simulated intestinal media (p<0.001). CONCLUSION: Significant increase in the dissolution rate of cocrystal was observed with no phase change in all formulations.