Poloxamer-based curcumin solid dispersions for ex tempore preparation of supersaturated solutions intended for antimicrobial photodynamic therapy

Abstract

Phototoxic effect of curcumin supersaturated solutions toward pathogenic bacteria has already been demonstrated. However, to be useful in the clinical practice, a supersaturated solution needs to be physically and chemically stabile over the relevant time period. Poloxamer-based solid dispersions (SD) intended for ex tempore preparation of a supersaturated solution were designed to simultaneously facilitate dissolution and inhibit precipitation of curcumin in vitro. Due to the transformation of the crystalline compound to an amorphous form, as shown by X-ray powder diffraction, the desired concentration of curcumin could easily be achieved upon hydration of SDs. The efficiency of selected poloxamers (Pluronic® F-127, F-68 and P-123) as the precipitation inhibitors (PIs) and influence of an additional PI (polyethylene glycol 400, hydroxypropyl methylcellulose, and hyaluronic acid) on the physical stability of the solutions were examined by UV–Vis spectrophotometry. HPLC-PDA was employed to evaluate hydrolytic and photolytic stability of curcumin in the SD solutions. At sub-micellar concentrations, Pluronics® F-127 and P-123, but not F-68, delayed curcumin precipitation in aqueous media and protected the compound from hydrolytic degradation up to 24 h. Complete inactivation of Enterococcus faecalis was achieved after exposure to solutions of selected SDs at curcumin concentration ≥1 µM and the light dose of 9.4 J/cm².

• Amorphous
• drug formulation
• Enterococcus faecalis, photodynamic therapy, polymers, precipitation inhibition

Acknowledgements

The authors thank Bente Amalie Breiby and Ivar Grove (School of Pharmacy, University of Oslo, Norway) and Inger Sofie Dragland (Nordic Institute of Dental Materials, Oslo, Norway) for technical assistance and Ellen Bruzell (Nordic Institute of Dental Materials, Oslo, Norway) for the fruitful discussions.

Declaration of interest

The authors report no declarations of interest.