Febuxostat solubilization and stabilization approach using solid dispersion method: Synergistic effect of dicalcium phosphate dehydrate and chitosan

Drug solubilization studies are continuously being conducted. Febuxostat (FBX) has a low solubility in water. This study aims to develop a stable FBX-solid dispersion (SD) formulation using a solvent evaporation method. The solubilization strategy of FBX is to develope an optimal FBX-SD formulation by selecting a solubilizer and carrier through the screening method. The final selected solubilizer, macrogol 15 hydroxystearate and polyoxyl 15 hydroxystearate (Kolliphor® HS-15), is widely used in the pharmaceutical industry as a nonionic solubilizing and emulsifying agent and has low toxicity. Especially when commonly used in developing lipophilic drug formulations, it dissolves well in water and ethyl alcohol.

Highlights

• The FBX-SD formulation (SD4; FBX:HS-15:DCP-D:UFL2:chitosan = 1:3:3:1:1 [w/w]) was prepared by solvent evaporation method.

• The SD4 formulation is clearly improved the dissolution (%) compared to that of Feburic® tab.

• The in vitro drug release and permeability in SD4 formulation were showed higher than Feburic® tab and PM4.

• The SD4 formulation is well maintained the stability for 6 months.

The optimal composition ratio of the formulation (SD4) was FBX:HS-15®:granular dicalcium phosphate dehydrate (DCP-D): A synthetic magnesium aluminometasilicate (Neusilin®UFL2):chitosan = 1:3:3:1:1 (w/w) and showed 3.0-, 2.3-, and 1.1-fold higher dissolution (%) of FBX compared to that of the Feburic tab® in pH 1.2 media, distilled water (DW), and pH 6.8 buffer, respectively. Also, in vitro release and in vitro permeability in SD4 formulation showed higher than that of Feburic tab®. Based on its stability over 6 months, it was confirmed that chitosan acted as a stabilizer. Moreover, due to weak intermolecular interactions, FBX in the SD4 formulation was considered to exist in a mixed state of amorphous and crystalline FBX. In conclusion, the improved dissolution (%) and stability of FBX in SD4 formulation were secured through the synergistic effect of excipients.

Read more

Jeong Sun Sohn, Jin-Seok Choi, Febuxostat solubilization and stabilization approach using solid dispersion method: Synergistic effect of dicalcium phosphate dehydrate and chitosan, International Journal of Biological Macromolecules, Volume 253, Part 5, 2023, 127266, ISSN 0141-8130,
https://doi.org/10.1016/j.ijbiomac.2023.127266.

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